Archive for June, 2024

Pictured: A scientist works behind an FDA sign/Taylor Tieden for BioSpace

The FDA approved 55 new drugs and 34 cell and gene therapies in 2023.But its not always good news that companies have to deliver to their stakeholders; the year also had its fair share of Complete Response Letters.

As we embark on 2024,BioSpaceis committed to keeping you up-to-date on all the FDAs actions in thisFDA Decision Tracker.

June 10

Product: Ipsen and Genfits Iqirvo

Indication: Primary biliary cholangitis

Monday, the FDA approved the first new drug in nearly a decade for primary biliary cholangitis: Ipsen and Genfits Iqirvo. A rare liver disease, PBC affects around 100,000 people in the U.S. and can lead to liver failure.

Iqirvo is intended to be used in combination with ursodeoxycholic acid (UDCA) in adult patients who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA.

The companies won accelerated approval for Iqirvo based on a reduction of alkaline phosphatase, a biochemical marker often used as a surrogate endpoint in PBC studies. Treatment with the drug demonstrated statistically significant improvements in biochemical response compared to UDCA alone, Christelle Huguet, executive vice president and head of research and development at Ipsen, said in a press release. An improvement in survival or prevention of liver decompensation events has not yet been shown, and the companies may need to run a confirmatory trial to verify Iqirvos clinical benefit.

June 10

Product: Almiralls Klisyri

Indication: Actinic keratosis

Dermatology company Almirall secured expanded approval of Klisyri for larger actinic keratosis-affected areas of the face or scalp. Klisyri can now be used to treat lesions up to 100 cm2 caused by the pre-cancerous dermatological condition, after safety and tolerability profiles were consistent with original pivotal trial results.

The new authorization for Klisyri, a microtubule inhibitor ointment, increases dosing for surface area treatment from up to 25 cm2 to up to 100 cm2, according to the companys press release.

In the same press release, Almirall Chief Scientific Officer Karl Ziegelbauer called the expanded approval a significant step forward for both patients and treating dermatologists, adding that the latter are looking for ways to treat the entire affected area to help prevent further lesion progression.

June 7

Product: Gerons Rytelo

Indication: Myelodysplastic syndromes

Geron Corporation kicked off the weekend on a high note as the FDA approval of its telomerase inhibitor Rytelo for myelodysplastic syndromes (MDS)a group of blood cancerssent the companys stock soaring more than 30%. Rytelo is specifically approved for MDS patients with transfusion-dependent anemia who do not respond to or are ineligible for the standard-of-care treatment, erythropoiesis-stimulating agents.

The approvalGerons first after 34 years in businesswas supported by data from the Phase III IMerge trial, in which patients on Rytelo had significantly higher rates of red blood cell transfusion independence over placebo for at least 24 weeks28% in the treatment arm versus 3% on placebo. For those who responded, this was sustained for a median of 1.5 years.

June 7

Product: GSKs Arexvy

Indication: Respiratory syncytial virus

People ages 5059 at an increased risk of severe outcomes from respiratory syncytial virus have a new preventative option after the FDA greenlit GSKs RSV vaccine Arexvy for this subgroup on Friday. Arexvy is indicated for the prevention of lower respiratory tract disease associated with RSV.

Fridays label expansionwhich was backed by strong immunogenicity and safety data in this populationextends the market reach for Arexvy, which became the first vaccine for RSV in May 2023, at that point intended for adults 60 and above.

GSK is also evaluating the vaccine for use in people 18-49 at increased risk of severe disease, and immunocompromised patients 18 and older.

May 31

Product: Modernas mRESVIA

Indication: Respiratory syncytial virus

Moderna has a second product on the market after the FDA approved mRESVIAformerly mRNA-1345to protect adults 60 years and older fromrespiratory syncytial virus (RSV). In a press release, Moderna CEO Stphane Bancel touted the strength and versatility of the companys mRNA platform, adding that the approval also marks the first time an mRNA vaccine has been approved for a disease other than COVID-19.

mRESVIA won approval based on the Phase III ConquerRSV trial, a global study of around 37,000 adults aged 60 or older in 22 countries, in which it displayed an efficacy rate of 83.7% against RSV lower respiratory tract disease. No serious safety concerns were identified in the trial.

May 30

Product: BMSs Breyanzi

Indication: Mantle Cell Lymphoma

After winning approval earlier this month in follicular lymphoma, Bristol Myers Squibbs Breyanzi got the FDA nod for another indication on Thursday: relapsed or refractory mantle cell lymphoma (MCL). Specifically, Breyanzi is approved for patients with MCL who have received at least two prior lines of systemic therapy, including a Bruton tyrosine kinase inhibitor.

The approval is backed by the results of the MCL cohort of TRANSCEND NHL 001, where treatment with Breyanzi elicited a 67.6% complete response rate in the target patient population.

Thursdays approval marks the fourth indication for Breyanzi, making it the CAR T cell therapy available to treat the broadest array of B-cell malignancies, according to BMSs press release.

May 29

Product: Eli Lillys Retevmo

Indication: RET-altered pediatric cancers

Eli Lilly won accelerated approval Wednesday for Retevmo to treat pediatric patients two years and older with RET-positive thyroid cancers and other solid tumors that carry the mutation. Retevmo is the first drug in the class available for children under 12 years of age, Pharmaphorum reported.

Retevmo is specifically indicated for advanced or metastatic medullary thyroid cancer with a RET mutation, advanced or metastatic thyroid cancer with a RET gene fusion untreatable with radioactive iodine therapy, and locally advanced or metastatic solid tumors with a RET gene fusion that have progressed after prior systemic treatment or have no treatment options, according to the publication.

The new approval for Retevmo, which was previously authorized to treat patients 12 and older with RET-positive thyroid cancers, is based on a single-arm study that showed an overall response rate of 48%, with a median duration of response not reached after 12 months of follow-up.

May 29

Product: Tris Pharmas Onyda XR

Indication: Attention deficit hyperactivity disorder

Wednesday, the FDA greenlit Tris Pharmas Onyda XR as the first non-stimulant medication for attention deficit hyperactivity disorder (ADHD) with a liquid formulation and nighttime dosing, according to the company. Onyda XR is a reformulation of clonidine hydrochloride, which was first approved by the FDA in 1974 to treat high blood pressure. Clonidine was approved for ADHD in 2010 under the brand name Kapvay, which is owned by Shionogi.

Onyda XR leverages Tris LiquiXR platform, producing a smooth, extended-release profile, per the biotech.

Approved for patients six years and older, Tris expects to have Onyda XR available in U.S. pharmacies by the second half of 2024.

May 29

Product: Tevas Austedo XR

Indication: Tardive dyskinesia and Huntingtons disease chorea

People with tardive dyskinesia and Huntingtons disease chorea have a streamlined treatment option after the FDA approved a new one-pill-a-day version of Tevas Austedo XR. The newly approved formulation offers more flexibility with the most once-daily doses of any vesicular monoamine transporter 2 (VMAT2) inhibitor, for these conditions, according to Tevas press release. Austedo XR comes in four tablet strengths: 30, 36, 42 and 48 mg.

Austedo XR, a once-daily extended-release formulation, was first approved in February 2023.

May 28

Product: Amgens Bkemv

Indication: Paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome

AstraZenecas rare disease drug Soliris now has a biosimilar on the market after the FDA greenlit Amgens Bkemv to treat paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). Bkemv was granted the FDAs interchangeability designation, which allows it to be used in place of the branded reference product without needing to change the prescription.

Like Soliris, Bkemv carries a boxed warning for meningococcal infections, which according to its label can be serious and life-threatening. Thus, it is only available through a restricted Risk Evaluation and Mitigation Strategies program.

May 16

Product: Amgens Imdelltra

Indication: Small cell lung cancer

Amgen secured approval Thursday for its first-in-class bi-specific T-cell engager, Imdelltra, for extensive-stage small cell lung cancer (SCLC). With the FDA nod, Imdelltra becomes the first bispecific T-cell engager therapy for advanced SCLC.

The accelerated approval was based on a Phase II study of 99 patients in the target population, where Imdelltra led to an overall response rate of 40% and a median duration of response of 9.7 months. Imdelltras label contains a boxed warning for serious or life-threatening cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome, according to the FDAs press release.

May 15

Product: BMSs Breyanzi

Indication: Follicular lymphoma

Bristol Myers Squibbs Breyanzi is now approved for the treatment of relapsed or refractory follicular lymphoma after the FDA granted a label expansion under its accelerated approval pathway. The approval was backed by data from the Phase II TRANSCEND FL study in which treatment with the CAR T cell therapy led to a 95.7% overall response rate, with a complete response rate of 73.4%.

Breyanzi, which first won approval in February 2021 for relapsed or refractory large B cell lymphoma, is also authorized to treat small lymphocytic leukemia and chronic lymphocytic leukemia. By May 31, the FDA is expected to decide whether to grant approval for the therapy in refractory mantle cell lymphoma.

May 14

Product: Dynavaxs Heplisav-B

Indication: Hepatitis B patients undergoing hemodialysis

The FDA declined to approve the supplemental Biologics License Application for Dynavax Technologies hepatitis B vaccine in patients undergoing hemodialysis, deeming the safety and efficacy data submitted by the company insufficient.

In its Complete Response Letter, the regulator said the data was insufficient because a third-party clinical site operator destroyed data source documents for about half of the subjects enrolled in the vaccines trial, according to Reuters.

While the vaccine, Heplisav-B, initially won approval for the prevention of hepatitis B in 2017, its path to the market was rocky, with two previous rejections in 2013 and 2016 for unresolved safety concerns, per Reuters.

May 1

Product: Boehringer Ingelheims Cyltezo

Indication: Rheumatoid arthritis, Crohns disease, ulcerative colitis and more

Theres another new biosimilar option to AbbVies blockbuster antirheumatic Humira. Wednesday, the FDA greenlit a high-concentration and citrate-free version of Boehringer Ingelheims Cyltezo, which was originally approved in October 2021. The newly approved dose is 100 mg/mL and is sold at a 5% discount to the branded reference product.

Cyltezo is indicated for all the same conditions as Humira, including moderate-to-severe rheumatoid arthritis, Crohns disease and ulcerative colitis. Wednesdays approval is backed by data from the Phase I VOLTAIRE-HCLF study, which compared the bioavailability of the high- and low-concentration (50 mg/mL) formulation of Cyltezo in 200 healthy volunteers.

April 30

Product: Neurocrine Biosciences Ingrezza

Indication: Huntingtons disease

A more convenient version of Neurocrine Biosciences Ingrezza will be hitting the market to treat tardive dyskinesia and chorea in Huntingtons disease after the FDA closed out April by approving a sprinkle capsule formulation of the drug.

Like the original capsule version, which was approved in 2017 for tardive dyskinesia and in 2023 for chorea in Huntingtons, Ingrezzas sprinkle formulation comes in 40-mg, 60-mg and 80-mg doses but is designed to be opened and sprinkled on soft foods. This format could be more accessible for patients who have trouble swallowing whole capsules, according to the Neurocrines announcement, which also noted that a survey of Huntingtons patients with chorea and their caregivers showed that 62% had difficulty swallowing due to their involuntary movements.

April 29

Product: Pfizer and Genmabs Tivdak

Indication: Cervical cancer

The FDA has converted the accelerated approval of Pfizer and Genmabs Tivdak into a full nod for recurrent or metastatic cervical cancer that has progressed on or after chemotherapy.

The antibody-drug conjugate (ADC), which was originally developed under a partnership between Seagen and Genmab, was granted accelerated approval in September 2021 based on a 24% objective response rate seen in the Phase II innovaTV 204 trial.

In the Phase III innovaTV 301 study, which enrolled more than 500 patients, Tivdak significantly boosted survival versus chemotherapy. An October 2023 readout showed the ADC cut the risk of death by 30% in patients with recurrent or metastatic cervical cancer; it also reduced the risk of death or worsening disease by 33% versus chemotherapy. No new safety signals were observed.

April 29

Product: X4 Pharmaceuticals Xolremdi

Indication: WHIM Syndrome

The FDAapprovedX4 Pharmaceuticals Xolremdi Monday as the first targeted treatment for WHIM syndrome, an ultra-rare immunodeficiency disease named for its four characteristics: warts, hypogammaglobulinemia, infections and myelokathexis.

Myelokathexis is a congential disorder of the white blood cells, and Xolremdi, an oral CXCR4 antagonist, is designed to mobilize white blood cells such as neutrophils, lymphocytes and monocytes from the bone marrow into the blood to improve immune deficiencies.

In the Phase III 4WHIM trial, Xolremdi showed a 60% reduction in annualized infection rate compared to placebo; trial participants had less than one infection per year compared with 4.5 for the placebo group. Patients saw an even greater reduction with additional time on treatment.

Its an exciting time for personalized medicine, and I think WHIM is going to be a poster child for rare diseases and the ability where were at now in modern medicine to design therapies to treat underlying genetic disorders, Teresa Tarrant, an associate professor at Duke Universitys School of Medicine and lead investigator of the 4WHIM trial, told BioSpace prior to Xolremdis approval.

April 26

Read more:
FDA Greenlights First Drug in Nearly a Decade for Rare Liver Disease - BioSpace

Patients

We screened 316 participants for eligibility (Fig. 1). Five pediatric patients (two girls and three boys) with bilateral congenital hearing loss caused by biallelic OTOF mutations were enrolled from 14 July 2023 to 15 November 2023 (Fig. 1 and Table 1). Details of Sanger sequencing results and OTOF variant interpretation in patients are provided in Extended Data Fig. 1 and Extended Data Table 1. The average auditory brainstem response (ABR) threshold was >95dB in all patients at baseline (Table 1). None of the patients received cochlear implants before the trial. A dose of 1.51012vector genomes (vg) AAV1-hOTOF per ear, selected on the basis of the previous unilateral study11, was subsequently injected into the bilateral cochleae of the patient through the round window during a one-time operation. We have completed a 26-week assessment in patients 1, 2 and 3, and a 13-week assessment in patients 4 and 5. The study is ongoing.

Five patients were enrolled to receive binaural gene therapy and were evaluated for the primary endpoint. CI, cochlear implant.

Source data

The primary endpoint was dose-limiting toxicity, defined as hematologic toxicity grade 4, nonhematologic toxicity grade 3 or aural toxicity grade 2 within 6weeks. The grade was assessed according to Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE V5.0). The dose of 1.51012vg AAV1-hOTOF was selected for bilateral treatment based on the results of the unilateral study that tested different doses11. No dose-limiting toxicity happened in five patients receiving binaural gene therapy with a dose of 1.51012vg AAV1-hOTOF per ear.

Efficacy outcomes include auditory function and speech perception. ABR, auditory steady-state response (ASSR), distortion product otoacoustic emission (DPOAE), and related questionnaires and tests were used to evaluate the auditory function, speech perception and sound source localization in patients.

At baseline, the average ABR threshold in the right (left) ear was >95dB (>95dB) in all five patients. In patient 1, the average ABR threshold in the right (left) ear was restored to 65dB (68dB) at 4weeks, 63dB (63dB) at 6weeks, 63dB (63dB) at 13weeks and 58dB (58dB) at 26weeks; the average ASSR threshold in the right (left) ear was 103dB (103dB) at baseline, and was restored to 48dB (63dB) at 4weeks, 53dB (58dB) at 6weeks, 53dB (58dB) at 13weeks and 53dB (58dB) at 26weeks (Fig. 2a). In patient 2, the average ABR threshold in the right (left) ear was >95dB (>95dB) at 4weeks, >85dB (>95dB) at 6weeks, 83dB (88dB) at 13weeks and 75dB (85dB) at 26weeks; the average ASSR threshold in the right (left) ear was 88dB (83dB) at 4weeks, 73dB (85dB) at 6weeks, 61dB (64dB) at 13weeks and 60dB (60dB) at 26weeks, compared with 79dB (81dB) at baseline (Fig. 2b). In patient 3, the average ABR threshold in the right (left) ear was restored to 63dB (63dB) at 4weeks, 63dB (60dB) at 6weeks, 60dB (58dB) at 13weeks and 55dB (50dB) at 26weeks; the average ASSR threshold in the right (left) ear was restored to 58dB (63dB) at 4weeks, 60dB (65dB) at 6weeks, 63dB (60dB) at 13weeks and 53dB (53dB) at 26weeks, compared with 100dB (100dB) at baseline (Fig. 2c). In patient 4, the average ABR threshold in the right (left) ear was >95dB (>95dB) at 4weeks, >90dB (>95dB) at 6weeks and 75dB (78dB) at 13weeks; the average ASSR threshold in the right (left) ear was restored to 95dB (95dB) at 4weeks, 85dB (85dB) at 6weeks and 63dB (60dB) at 13weeks, compared with 106dB (106dB) at baseline (Fig. 2d). In patient 5, the average ABR threshold in the right (left) ear was restored to 68dB (75dB) at 4weeks, 70dB (68dB) at 6weeks and 63dB (63dB) at 13weeks; the average ASSR threshold in the right (left) ear was restored to 68dB (71dB) at 4weeks, 60dB (65dB) at 6weeks and 60dB (63dB) at 13weeks, compared with 85dB (88dB) at baseline (Fig. 2e).

ae, The ABR and ASSR thresholds of patients 1 (a), 2 (b), 3 (c), 4 (d) and 5 (e). The arrows indicate no response even at the maximum sound intensity level. Arrows pointing left and downward, right ear; arrows pointing right and downward, left ear.

In both ears of patients 13, the signal-to-noise ratio (SNR) of DPOAE decreased at most frequencies at 4weeks and gradually recovered at the later follow-up (Extended Data Fig. 2ac). In patient 4, the SNR was stable at some frequencies at 4weeks, decreased to some extent at later follow-up and has not recovered at 13weeks (Extended Data Fig. 2d). In patient 5, the SNR decreased at some frequencies at 6weeks and recovered to some degree at 13weeks (Extended Data Fig. 2e).

In patient 1, the Meaningful Auditory Integration Scale (MAIS) and Categories of Auditory Performance (CAP) scores were 1 and 0, respectively, at baseline, and 28 and 4, respectively, at 26 weeks; the Speech Intelligibility Rating (SIR) and Meaningful Use of Speech Scale (MUSS) scores were 1 and 0, respectively, at baseline, and 1 and 7, respectively, at 26 weeks. The Speech of the Speech, Spatial, and Other Qualities of Hearing Scale for Parents (SSQ-P), the Spatial of the SSQ-P and the Other Qualities of the SSQ-P scores were 0.3, 0 and 0, respectively, at baseline, and were improved to 7.8, 2.8 and 5.0, respectively, at 26weeks (Table 2). In a quiet environment, the perception of monosyllable, disyllable and sentence was all 0% at baseline and 2.0%, 1.4% and 0%, respectively, at 26weeks after treatment; ambient sound, tone, initial and final was all 0% at baseline, and 31.3%, 31.3%, 20.8% and 20.8%, respectively, at 26weeks (Extended Data Table 2). For sound source localization tests, the bilateral root mean square error (RMSE) was 92.81.1 at baseline and 40.01.7 at 26weeks; when one ear was covered, the unilateral RMSE (75.51.0) at 26weeks was worse (Extended Data Table 2). In Supplementary Video 1, patient 1 could not hear at baseline and could recognize sound 4weeks and 6weeks after injection. At 13weeks, she could speak syllables such as a, ba (father), i, u, s and ma (mother). She was able to complete the sound localization test well at 13weeks.

In patient 2, the InfantToddler MAIS (IT-MAIS) and CAP scores were 0 and 0, respectively, at baseline, and 35 and 5, respectively, at 26 weeks; the SIR and MUSS scores were 1 and 0, respectively, at baseline, and 2 and 9, respectively, at 26 weeks; the Speech of the SSQ-P, the Spatial of the SSQ-P and the Other Qualities of the SSQ-P scores were all 0 at baseline and 6.7, 5.3 and 8.5, respectively, at 26weeks (Table 2). In Supplementary Video 2, patient 2 could not respond to sound and music at baseline, but he was able to turn to the sound source when his name was called from the left and right of his backward side 6weeks after injection. He could dance to the music and complete some simple instructions at 15weeks, and he could say some simple words, for example, ayi (aunt) and bai (bye), and communicate with others at 26weeks.

In patient 3, the IT-MAIS or MAIS, and CAP, scores were all 0 at baseline, and 35 and 5, respectively, at 26weeks; the SIR and MUSS scores were 1 and 0, respectively, at baseline, and 2 and 15, respectively, at 26weeks; the Speech of the SSQ-P, the Spatial of the SSQ-P and the Other Qualities of the SSQ-P scores were all 0 at baseline, and 7.3, 8.0 and 8.5, respectively, at 26 weeks (Table 2). In Supplementary Video 3, patient 3 had no response to sound and music at baseline, but he could turn back when his name was called 3weeks after injection. At 13weeks, he was able to move his body and dance when he heard the music. He was able to say some simple words at 26weeks, such as baba (father), nainai (grandmother) and yeye (grandfather).

In patient 4, the MAIS and CAP scores were 2 and 0, respectively, at baseline, and 16 and 4, respectively, at 13weeks; the SIR and MUSS scores were 1 and 2, respectively, at baseline, and 1 and 7, respectively, at 13weeks; the Speech of the SSQ-P, the Spatial of the SSQ-P and the Other Qualities of the SSQ-P scores were 0.3, 0 and 0, respectively, at baseline, and 3.6, 5.8 and 4.5, respectively, at 13weeks (Table 2). In Supplementary Video 4, patient 4 had no response to sound at baseline, but she could turn back when her name was called 4weeks after injection. She could complete some instructions at 13weeks, and she could say simple words at 20weeks, for example, baba (father), mama (mother) and nainai (grandmother).

In patient 5, the IT-MAIS or MAIS, and CAP, scores were 2 and 0, respectively, at baseline, and 29 and 4, respectively, at 13weeks; the SIR and MUSS scores were 1 and 0, respectively, at baseline, and 2 and 7, respectively, at 13weeks; the Speech of the SSQ-P, the Spatial of the SSQ-P and the Other Qualities of the SSQ-P scores were 0.2, 0 and 0, respectively, at baseline, and 7.6, 7.2 and 6.6, respectively, at 13weeks (Table 2).

To minimize the potential inflammatory response, dexamethasone was used intravenously for 8days starting from 3days before AAV1-hOTOF bilateral injection. No serious adverse event (AE) occurred. A total of 36 AEs occurred (Table 3), including emesis (patient 1), fever (patient 2), increased lymphocyte counts (patients 14), decreased lymphocyte counts (patient 3), decreased neutrophil counts (patient 2), decreased hemoglobin levels (patients 2 and 3), increased triglyceride levels (patient 2), increased cholesterol levels (patients 25), transient reduction in fibrinogen levels (patient 3), increased creatine phosphokinase levels (patient 2), decreased haptoglobin levels (patients 1 and 5), increased lactate dehydrogenase levels (patients 25), hyperglycemia (patient 5), proteinuria (patient 1) and hematuresis (patients 1 and 4). All 36 AEs were grade 1 or 2. The most common AEs were increased lymphocyte counts (6 out of 36) and increased cholesterol levels (6 out of 36), followed by increased lactate dehydrogenase levels (5 out of 36). In patient 1, emesis occurred at 2h after injection and was resolved with symptomatic treatment within 1day. In patient 2, fever (highest temperature, 38.7C) occurred at 18days and 29days after injection, with mild cough and increased lymphocyte counts, but no evidence of pneumonia or other concomitant symptoms.

In addition, the structure of the ears was observed by computed tomography and magnetic resonance imaging, showing the normality of the ear structure after injection (Extended Data Figs. 3 and 4).

Neutralizing antibodies against AAV1 were increased in all patients at 6weeks after treatment (Extended Data Table 3). Vector DNA in the blood was not detectable in any patient at 7days after treatment (Extended Data Table 3). Interferon gamma (IFN-) enzyme-linked immunosorbent spot (ELISpot) responses to AAV1 capsid peptide pools with peripheral blood mononuclear cells (PBMCs) drawn from each patient at 6weeks after AAV1-hOTOF binaural gene therapy were negative (Extended Data Fig. 5)

See the original post:
Bilateral gene therapy in children with autosomal recessive deafness 9: single-arm trial results - Nature.com

Inspiration sparked by shaving

Stephan co-founded Tidal Therapeutics to help commercialize his immune-cell programming nanoparticles (acquired by Sanofi in 2022). His lab needed a new direction, and inspiration struck one morning as he watched his freshly sprayed shaving foam expand in his palm.

I thought, Let's explore foam, Stephan said. Maybe we can make a formulation of foam that is not like the foam in in our shaving foam, but something that is biocompatible, to deliver therapeutics.

The froth had properties that would be attractive in a drug-delivery vehicle. Its volume started small, but puffed up. The foam stayed where it was sprayed, and didnt slide away. These characteristics could help get a therapeutic into contact with more critical cells while also ensuring that it didnt slip away.

Trying new substances or approaches that come from things in everyday life that you wouldn't necessarily associate in medical applications is sometimes a really interesting way to drive down costs and deliver drugs more easily, Fitzgerald said. But it was definitely a little bit out of my wheelhouse.

Foam-as-medical-delivery method isnt without precedent, Stephan noted. Foam-based delivery already enhances certain applications like delivery of hemorrhoid medication and intra-uterine imaging.

But could foam enhance gene therapy?

To create a bio-compatible foam, Stephan and his team initially took inspiration from the food industry.

Cocktails, ice cream, yogurt: they know how to make things foamy, he said.

Stephan Lab members, including staff scientist Sirka Stephan, PhD, started experimenting with ingredients available from the pantry store, he said.

Importantly, these materials are dead cheap, Stephan said. Theyre available for pennies. Theyre manufactured at large scale, and because theyre already used for pharmaceutical applications like coating tablets theyre available pharmaceutical-grade.

The scientists formulated a solution of methylcellulose (a food binder) and xanthan gum (a food thickener) that, when aerated using two lab syringes, bubbles into an easy-to-apply froth.

But did it have the potential to improve gene therapy?

We started with a lot of hypotheses in terms of, could foam potentially concentrate our gene therapy, keep it more localized, and help it stay in the tissue where we wanted to adhere? Fitzgerald said. My job was to do the experiments to prove the hypotheses.

Foam has certain properties that make it an attractive drug-delivery vehicle. Its more than tightly packed air bubbles: In a foam, the bubbles are separated and surrounded by incredibly thin layers of continuous liquid, called lamellae. Active ingredients become highly concentrated in these lamellae, which allows foam to deliver highly concentrated doses of medicine to large areas, even if the total dose is small.

View original post here:
Taking a frothy risk to advance gene therapy - Fred Hutchinson Cancer Center

Family members noticed initial signs that their children could recognize sounds two weeks after application of the therapy.

(CN) Five children born deaf can now hear in both ears after a trial of a novel gene therapy focused on repairing a hereditary dysfunction that prevents auditory signals from reaching the brain, according to authors of a study published in the journal Nature Medicine Wednesday.

The success of the therapy in both ears demonstrates that the treatment can restore a full range of hearing functions including identifying the locations of sounds, recognizing specific sounds in noisy environments and the ability to perceive and develop speech.

The researchers used a minimally invasive surgical procedure to inject vector viruses into the inner ear. The viruses transfer genes into specialized cells that convert physical sound waves into the electrical signals that can be transmitted by nerve cells.

The new genetic material allows the cells to correctly replicate a protein that is necessary to send the converted electrical signals from the inner ear to the brain.

Family members noticed initial signs that their children could recognize sounds two weeks after application of the therapy. All the children were born deaf, four of them were between one and three years of age and the fifth participant was an 11-year-old.

At four to six weeks the children would turn to face the sound when a parent called to them from outside of their plane of view. At 13 to 15 weeks children could dance to music and form simple syllables, and at 26 weeks the children used complete words and showed more advanced communication.

Its very emotional for the whole family and even for my team, some of my students were so touched that they began to cry, said lead study author Dr. Yilai Shu, director of the Diagnoses and Treatment Center of Genetic Hearing Loss affiliated with the Eye and ENT Hospital of Fudan University in Shanghai.

The successful trials grew out of a collaboration between Shu and the studys co-senior author Zheng-Yi Chen, associate scientist in the Eaton-Peabody Laboratories at Mass Eye and Ear in Boston. Shu was a student of Chens and they worked together during Shus postdoctoral fellowship at Mass Eye and Ear. Shu returned to China over a decade ago, but the two scientists continued to collaborate.

The research team conducted the trials at the Eye and ENT Hospital of Fudan in Shanghi, China.

The five children that participated have a specific genetic disorder caused by the mutation of a single gene that prevents the cells in the inner from replicating the protein otoferlin that is crucial for sound signal transmission via the nervous system.

Globally, 430 million people have some form of disabling hearing loss, according to the World Health Organization. About 26 million people were born with hearing loss and 60% of those cases are due to genetic factors, the study's authors say.

This really opens a new era in treating hearing loss because there are over 150 genes that can cause genetic deafness, Shu said.

In animal trials, the research team has shown that gene therapies are effective in treating several of these forms of genetic deafness, said Chen. The teams successful treatment of the otoferlin genetic deficiency in humans means that the other models with proven success in animals can now move into human trials.

Eventually, the researchers hope to develop gene therapies for noise and age-related deafness as well.

One of the challenges of using the viral vector gene therapy with the otoferlin gene is that the gene itself is too large for the virus to carry, said Shu. To overcome this the researchers used a new technique that involves splitting the gene in half and allowing viruses to carry each half into the cells where the gene can recombine.

This is actually a technology breakthrough, said Chen, So many genes for human diseases are also very big so this approach can be broadly applied in gene therapies to treat other diseases, not only deafness.

In January the research team published the results of a trial conducted in 2022 which successfully tested the therapy in one ear. The bilateral trial involving two ears, which has allowed for participants to recover a full range of hearing functions including ability to detect the location of sound, requires a procedure for each ear resulting in an increased dosage of the viral vector.

The researchers choose to test the therapy in one ear first because the additional dosage of the viral vector is more likely to trigger an immune response which can lead to adverse affects. All five children involved in the bilateral study recovered their hearing and the adverse affects that researchers detected such as fever or elevated white blood count were well below the safety threshold.

Chen, who is also an associate professor of OtolaryngologyHead and Neck Surgery at Harvard Medical School said that international cooperation has been important to developing the treatment and Shu agrees.

This type of research is very difficult and relies on decades of international study, Shu said.

We want to use this as an example that there is a future for this kind of collaboration, Chen said. Its not a political issue its really just for human health and a common benefit for all of us.

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Children born deaf react to sound after successful gene therapy trial - Courthouse News Service

The first clinical trial to administer gene therapy to both ears in one person has restored hearing function to 5 children born with a form of inherited deafness, astounding the research team..

Two of the children even gained an ability to appreciate music.

The success of the new approach is detailed in a new study published in Nature Medicine. The workbuilds on the first phase of the trial, published earlier this year, in which children were treated in a single ear.

The results from these studies are astounding, says study co-senior author Zheng-Yi Chen, an associate scientist in the Eaton-Peabody Laboratories at Massachusetts Eye and Ear in the US.

We continue to see the hearing ability of treated children dramatically progress and the new study shows added benefits of the gene therapy when administrated to both ears, including the ability for sound source localisation and improvements in speech recognition in noisy environments.

Lead author Yilai Shu, an attending doctor in otolaryngologyand an investigator at Eye and Ear, Nose, Throat hospital of Fudan University, China, says: restoring hearing in both ears of children who are born deaf can maximise the benefits of hearing recovery.

These new results show this approach holds great promise and warrants larger international trials.

The children involved in the study were born with DFNB9, which accounts for between 2 and 8% of hereditary deafness. It is caused by mutations in the OTOF gene which prevent the production of functioning otoferlin protein, which can significantly reduce sound transmission from the inner ear hair cells to hearing nerves.

Through minimally invasive surgery, Shu injected adeno-associated virus (AAV) engineered to carry and deliver functioning copies of the human OTOF transgene, into the childrens inner ears.

All 5 children were observed over a 13 or 26-week period and showed hearing recovery in both ears, with dramatic improvements in speech perception and sound localisation.

During follow-up, 36 adverse events were observed, the most common being increased white blood cell counts and increased cholesterol levels. However, there were no dose-limiting toxicity or serious adverse events.

The trial is continuing, and participant are stillbeing monitored.

The authors say their results show that the gene therapy is feasible, safe, and efficacious.

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Gene therapy restores hearing to children with inherited deafness - Cosmos

Visiongain has published a new report entitled Gene Therapy R&D Market Report 2024-2034: Forecasts by Disease (Cancer, Rare Diseases (Oncologic, Non-oncologic), Cardiovascular Diseases, Ophthalmic Diseases, Haematology, Neurological, Diabetes Mellitus, Other)), by Vector (Viral (Retrovirus, Adenovirus, AAV, Lentivirus, Others), Non-viral (Naked DNA, Gene Gun, Electroporation, Lipofection)), by Techniques (Gene Augmentation Therapy, Gene Replacement Therapy), by Participants (Small/Medium Pharma & Biotech, Universities & Research Institutes, Hospitals, Government & Public Bodies, Big Pharma) AND Regional and Leading National Market Analysis PLUS Analysis of Leading Companies AND COVID-19 Impact and Recovery Pattern Analysis.

The gene therapy R&D market is estimated at US$3,641.7 million in 2024 and is projected to grow at a CAGR of 29.8% during the forecast period 2024-2034.

Gene Therapy: Shaping Tomorrow's Healthcare Landscape Through Innovation and Investment

Over the past five years, gene therapy has seen a remarkable resurgence fuelled by significant strides in virology, vector and capsid architecture, and manufacturing technologies. These advancements have sparked a surge in promising outcomes, attracting the attention of biotech investors and reigniting interest in the field. This renewed enthusiasm has spurred a flurry of strategic manoeuvres among biopharma firms vying for an edge in this burgeoning market.

Recent advancements in gene therapy are grounded in a deeper comprehension of viral vectors, pivotal for delivering therapeutic genes to target cells. Refinements in vector design and capsid engineering have bolstered the efficiency, specificity, and safety of gene delivery. Concurrently, progress in manufacturing processes has bolstered the scalability and consistency of gene therapy products, enabling the production of treatments for larger patient cohorts.

The market for gene and cell therapies (CGTs) is expanding rapidly, with over 1,400 companies globally focusing on CGTs and more than 3,500 therapies in preclinical and clinical development. Presently, there are over 2,000 active clinical trials, with North America leading with 964 trials, trailed by the Asia Pacific with 848, Europe with 244, and other regions with 139 active trials. Oncology and rare diseases emerge as the primary therapeutic domains targeted by CGTs, underlining the potential to address unmet medical needs and furnish innovative treatment avenues.

Investment in the CGT sector remains robust, with venture capital financing being the primary growth catalyst. The persistent inflow of capital underscores a strong belief in scientific breakthroughs and the potential to revolutionize the treatment landscape for a spectrum of diseases, encompassing both rare and common ailments.

Despite significant progress and optimism surrounding gene therapy, the field confronts several challenges, including high treatment costs, intricate regulatory requisites, and the imperative for long-term safety and efficacy data. Tackling these obstacles demands sustained collaboration among industry stakeholders, regulatory bodies, and the scientific community.

Looking ahead, the future of gene therapy holds promise. Ongoing technological advancements, coupled with substantial investment and supportive regulatory frameworks, are poised to propel further innovations and broaden the therapeutic applications of gene therapy. As the industry matures, gene therapy stands to revolutionize the treatment paradigm for a diverse array of diseases, offering newfound hope to patients who previously faced limited or no treatment options.

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How has COVID-19 had a Significant Impact on the Gene Therapy R&D Market?

The COVID-19 pandemic fundamentally transformed the Gene Therapy Research and Development (R&D) market, presenting a combination of challenges and opportunities that both accelerated and impeded progress. On the positive side, the urgent demand for COVID-19 treatments and vaccines spurred technological advancements, particularly in mRNA and viral vector technologies crucial to gene therapy. This urgency drove unprecedented levels of funding, collaboration, and resource allocation, fostering innovation and expediting the translation of gene therapy concepts into clinical applications. Regulatory bodies responded by streamlining approval processes for urgent therapies, potentially benefiting future gene therapy products.

The pandemic underscored the importance of robust manufacturing and distribution networks, prompting significant investments in scaling up production capabilities for gene therapies. Conversely, the pandemic caused substantial disruptions in clinical trials, with many studies delayed or halted due to lockdowns, travel restrictions, and the prioritization of COVID-19 related research, leading to setbacks in project timelines. Supply chain interruptions also impacted the availability of critical materials and reagents, complicating R&D efforts. Despite these challenges, the pandemic highlighted gene therapy's potential to address genetic disorders and emergent viral threats, reinforcing its strategic importance. The industry's resilience and adaptability were evident in its response, suggesting that the lessons learned will strengthen future gene therapy R&D efforts.

Furthermore, the pandemic emphasized the importance of global collaboration, with international partnerships playing a crucial role in accelerating the development and distribution of new technologies. Consequently, the gene therapy market is poised for sustained growth, driven by technological advances made during the pandemic and increased recognition of the value of rapid, adaptable therapeutic development platforms. Overall, while the COVID-19 pandemic presented significant obstacles, it also served as a catalyst for innovation and structural improvements within the gene therapy R&D landscape, positioning the industry for a stronger and more agile future.

How will this Report Benefit you?

Visiongains 340-page report provides 156 tables and 192 charts/graphs. Our new study is suitable for anyone requiring commercial, in-depth analyses for the gene therapy R&D market, along with detailed segment analysis in the market. Our new study will help you evaluate the overall global and regional market for Gene Therapy R&D. Get financial analysis of the overall market and different segments including disease, vector, techniques, participants, and capture higher market share. We believe that there are strong opportunities in this fast-growing gene therapy R&D market. See how to use the existing and upcoming opportunities in this market to gain revenue benefits in the near future. Moreover, the report will help you to improve your strategic decision-making, allowing you to frame growth strategies, reinforce the analysis of other market players, and maximise the productivity of the company.

What are the Current Market Drivers?

Robust Gene Therapy Pipeline Anticipated to Boost Growth

Cell and gene therapies (CGTs) are transitioning from research labs to clinical settings, offering targeted treatments for specific diseases, unlike the broader targets of small-molecule therapies. These therapies aim to introduce healthy cells or correct genetic defects in patients, with cancer emerging as a primary focus, representing nearly half of all CGTs in clinical trials.

One promising approach is CAR-T therapy (Chimeric Antigen Receptors), which combines cell and gene therapy to combat cancer. By modifying a patient's immune cells' DNA, CAR-T therapy enhances their ability to recognize and attack cancer cells. FDA approval for two CAR-T therapies signifies their efficacy, particularly for cancer patients with limited treatment options. Continued research endeavours hold the potential to expand the availability and efficacy of these therapies across a broader spectrum of cancers.

Recent data show a notable increase in gene therapies entering Phase III trials, signalling progress and momentum in this field.

Technological Advancements Projected to Fuel Market Growth

Gene therapy, both as a cutting-edge medical technique and a burgeoning biomedical business, holds a promising future propelled by technological advancements and industry promotion. While genome editing technologies enable precise manipulation of specific genes within DNA sequences, concerns regarding off-target effects, which may inadvertently edit genes with similar sequences, pose challenges such as tumorigenicity. Despite these challenges, genome editing offers the potential for lasting genomic changes, albeit with careful consideration of safety implications.

Moreover, the market for digital bioprocessing technology is driven by the demand for reproducible, efficient, and cost-effective development of cell and gene therapies. These advancements are pivotal for realizing the commercial potential of these therapies in the coming years, enhancing market penetration, and reducing overall therapy costs. Notably, breakthroughs like the use of gold nanoparticles for gene therapy delivery by researchers at the Fred Hutchinson Cancer Research Center signify promising alternatives to conventional delivery methods, potentially revolutionizing scalability and accessibility.

CRISPR-Cas9, a transformative genome editing tool, is revolutionizing scientific research with its versatility, speed, cost-effectiveness, and accuracy compared to previous methods. Its applications span across animal research, human gene therapy, medical research, and plant science, facilitating precise gene targeting, alterations, insertions, deletions, and single base pair conversions. As breakthroughs in this field continue to unfold, the gene therapy R&D market is poised for significant growth in the forecast period.

Get Detailed ToC https://www.visiongain.com/report/gene-therapy-market-2024/

Where are the Market Opportunities?

Artificial Intelligence Can Bring Value to Gene Therapy R&D

While fully AI-generated drug discovery hasn't yet yielded approved drugs, the number of drugs in development with AI-associated platforms is steadily increasing. In 2023 alone, at least 19 drugs attributed to AI were in clinical development, with potential advancement in the clinical pipeline anticipated for 2024.

AI holds significant potential in various stages of cell and gene therapy R&D, with McKinsey & Company identifying its greatest impact in target identification, payload design optimization, and translational and clinical development. For instance, AI and machine learning (ML) enhance target selection to optimize therapeutic success.

In viral therapeutics aiming for genome editing, algorithms predicting CRISPR target sites aid in identifying genomic locations conducive to efficient editing with minimal off-target activity. For mRNA-based vaccines, AI predicts tumour epitopes for therapeutic molecule binding. Similarly, in CAR T-cell therapies, AI facilitates antigen and binding site identification, enhancing CAR design for improved activity and reduced cytotoxicity.

AI and ML models rapidly screen numerous candidates and select designs meeting desired criteria, especially when integrated into an AI-enabled closed-loop research system. This system automatically feeds initial screening results into an ML pipeline, which learns from computational features to suggest optimized payload candidates for experimentation. Experimental data then feed back into the system, perpetuating learning and closing the research loop.

In translational and clinical development, AI and ML mitigate safety risks in clinical trials by identifying translational biomarkers indicative of success, selecting appropriate patients, estimating optimal dosing, and predicting severe adverse events based on patient profiles and real-world data from similar treatments.

Facility Expansion Anticipated to Offer Lucrative Growth Prospects

The surge in clinical-stage start-ups has led to a scarcity of viral vector manufacturing capacity among contract manufacturers, upon which new gene and cell therapy companies heavily rely for early-stage development. As these firms mature into commercial entities, they often opt for in-house manufacturing to circumvent outsourcing complexities. Consequently, biotech companies are formulating growth strategies, establishing internal teams, and seeking site consultant assistance. These experts aid in the rigorous search for suitable lab and development facilities, or, increasingly, in securing new construction sites in tight real estate markets.

These internal capabilities empower gene and cell therapy companies to swiftly scale up production from clinical batches to commercial scale, even during the research and development phase. Moreover, co-locating with drug research and development operations facilitates seamless technology transfer and minimizes disruption, especially during clinical trials.

The imperative for expedited "time-to-market" underscores the focus on existing buildings, which are increasingly scarce in established biotech hubs due to market demand. These hubs offer advantages such as tailored university programs and engagement with other gene and cell therapy companies, both as competitors and potential collaborators, creating a fertile environment for talent acquisition. While cost sensitivity is paramount for all ventures, venture-funded enterprises are particularly keen on cost reduction, necessitating efforts to minimize both upfront and ongoing cash outlays.

Competitive Landscape

The major players operating in the gene therapy R&D market are Astellas Pharma Inc., American Gene Technologies, Applied Genetic, Bayer, Benitec BioPharma, Biogen, Bluebird Bio, Bristol Myers Squibb, Calimmune, Inc. (CSL Behiring), Cellectis, GenSight Biologics, Gilead Lifesciences, Inc., Novartis AG, Orchard Therapeutics, Oxford Biomedica, Pfizer, Inc., REGENXBIO Inc., Sangamo Therapeutics, Inc., Sanofi, Spark Therapeutics (Subsidiary of Roche), Takeda Pharmaceuticals, Transgene, UniQure N. V., Voyager Therapeutics, ViGeneron, GQ Bio Therapeutics GmbH, OCUGEN, INC., Taysha GTx, and Sarepta Therapeutics, Inc.. These major players operating in this market have adopted various strategies comprising M&A, investment in R&D, collaborations, partnerships, regional business expansion, and new product launch.

Recent Developments

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Gene Therapy R&D market is projected to grow at a CAGR of 29.8% by 2034: Visiongain - GlobeNewswire

All five children taking part in a Shanghai-led clinical trial of a gene therapy to treat congenital hearing loss showed significant restoration of hearing in both ears, researchers said on Wednesday.

Their speech function and ability to locate the sources of sound were also greatly improved, researchers from the Eye and ENT Hospital of Fudan University in Shanghai said.

It was the world's first clinical trial of a gene therapy for both ears, they said.

The children, aged between 1 and 11, all have autosomal recessive deafness 9, mainly caused by mutation of a particular gene, OTOF. The research team injected gene therapy medicine developed in its previous studies into both ears of the patients in the same session, using minimally invasive and microscopic injection methods.

"Good safety of the therapy was demonstrated during their follow-up observations, proving that the binaural gene therapy with the treatment known as AAV1-hOTOF was safe and effective," said Shu Yilai, one of the leading researchers and director of the inherited deafness diagnosis and treatment center affiliated with the Shanghai hospital.

A paper about their research, a joint effort with Harvard Medical School associate professor Zheng-Yi Chen, was published recently in the journal Nature Medicine.

There are an estimated 26 million people with congenital hearing loss worldwide, and approximately 30,000 infants are born with the condition in China each year. Experts said that 60 percent of them are related to genetic factors, which severely damage their speech, cognition and intellectual development. There is, as yet, no effective clinical therapy.

People with the OTOF mutation usually suffer from severe or even complete hearing loss and speech impairment. In China, among the infants and young children diagnosed with auditory neuropathy spectrum disorder, up to 41 percent have a mutation in the OTOF gene.

Gene therapy is widely considered by experts to be one of the most promising strategies for curing hereditary deafness. It can deliver genes with normal function directly to the inner ear through a delivery vehicle, fundamentally restoring or improving hearing for such patients, the research team said.

It began recruiting participants from China for the clinical trial to receive treatment in one ear in October 2022, and completed the treatment of the first patient outside China in December that year.

Six patients were included in the trial to receive gene therapy in one ear, and the longest follow-up time for a participant has now reached 17 months, with the young patient later able to hold daily conversations.

Shu shared the clinical trial data at the annual conference of the European Society of Gene and Cell Therapy, one of the world's most authoritative international academic conferences in the field of gene and cell therapy, in Belgium in October.

The results of the clinical research that used gene therapy in one ear were published in The Lancet in January. International peers said it could open a new era for treating hearing impairment and even more diseases through gene therapy.

The clinical trial of the gene therapy in both ears began recruiting participants in July last year.

"We took a step further to try to restore the natural ability of human hearing in both ears for the patients," Shu said. "It'll also help to restore their ability to hear three-dimensional sound, locate sound sources, and distinguish speech in the context of noise."

He shared the latest progress in the trial with experts and scholars from around the world during the annual conference of the American Society of Gene& Cell Therapy held last month in Baltimore in the United States.

Read this article:
Gene therapy improves deaf children's hearing - ecns

Five children with congenital deafness have had their hearing significantly improved after receiving gene therapy, the Eye, Ear, Nose and Throat Hospital of Fudan University said on Wednesday.

The children, between the ages of 1 and 11 all suffered hereditary deafness due to a genetic mutation.

Around 30,000 children are born deaf in China each year with 60 percent of cases related to genetic defects, seriously impacting their language, cognition and intelligence development. There is no effective medication so far.

Gene therapy is a promising treatment for hereditary deafness, taking effect by injecting properly functioning genes directly into the inner ear.

Dr Shu Yilai led his team at the hospital to develop a genetic medicine targeting deafness due to the mutation with a precise and minimally invasive drug delivery route and equipment.

Since December 2022, six children have received an injection to one ear. The first, who has been followed for a year and five months, has been able to develop proper daily communication.

To achieve a bigger benefit to patients and help them regain their hearing and build 3D and accurate auditory localization, doctors started gene therapy on patients' both ears in July 2023.

The world's first gene therapy on deafness genes in both ears has testified to the safety and effects of gene therapy in congenitally deaf people and greatly boosts its development, showing a strong potential of gene therapy in congenital deafness treatment, experts said.

The research was published by world-leading journal Nature Medicine.

The research is published in world-leading journal Nature Medicine.

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Gene therapy in both ears proves a success for deaf children - SHINE News

Cryonics startup Cradle was unveiled this week, boasting $48 million in funding and a mission to develop and prove the feasibility of whole-body reversible cryopreservation. Co-founded by venture capitalist and longevity pioneer Laura Deming and chief scientist Hunter C Davis, the company is built on the belief that pausing and restarting biological functions on demand is a solvable problem.

Were building reversible cryo technologies, said Deming in a post on X. Think the hibernation pods you see in space movies for long-term travel we want to build that.

Cradles approach to cryopreservation focuses on pausing molecular motion through cooling, thus preventing tissue damage that typically occurs during freezing. This concept leverages technologies like those used in in vitro fertilization (IVF), where embryos can be stored at cryogenic temperatures for extended periods.

By adapting and scaling these principles, Cradle seeks to achieve cryopreservation of larger biological systems, including human organs and potentially whole bodies. The companys web site states We are optimistic that human whole-body reversible cryopreservation is solvable.

Cradle has identified three areas of medicine that it believes its technology can potentially benefit. First, by cryopreserving neural tissue, the company aims to improve the accessibility of human brain tissue samples for research, potentially accelerating drug development and neuroscience research. Second, Cradle believes that cryopreservation could extend the viability window for donor organs, allowing more time for testing and matching, thereby reducing rejection rates and improving transplant outcomes. And finally, the company suggests its technology could allow patients with terminal illnesses to pause their biological time, giving them the opportunity to survive until effective treatments become available.

Cradle said its first major milestone, achieved in February 2024, involved recovering electrical activity in a cryopreserved and rewarmed slice of rodent neural tissue. The company claims this breakthrough serves as a foundational proof of concept, paving the way for its more ambitious goals.

Next steps for Cradle include demonstrating preserved synaptic function and long-term potentiation in cryopreserved neural tissue, and eventually, achieving functional preservation of whole organs and even entire organisms. The companys stated milestones include:

To achieve its objectives, Cradle says it is developing sophisticated engineering systems for vascular perfusion, vitrification, and rapid rewarming. Additionally, the company is working on new cryoprotectant molecules that address the toxicity issues associated with current approaches, as well as developing assays to measure neural tissue viability post-cryopreservation and creating surgical protocols for preparing organs and organisms for the process.

While the concept of reversible full-body cryopreservation may sound like science fiction to some, Deming addresses the doubters on Cradles web site, stating, I feel incredibly angry when I find problems which could help patients, but which arent worked on because they seem uncool or havent been well evaluated. I think we, as humans, should try as hard as we can to find the best path to cures for patients, and to look past cognitive biases that get in the way of perceiving them correctly.

Well be following developments at Cradle and across the cryopreservation space with great interest!

Read the rest here:
Cradle emerges with $48m to build reversible cryonics technology - Longevity.Technology

In recent weeks, Southern Cryonics the southern hemispheres only cryopreservation facility, located in rural New South Wales announced it had successfully cryopreserved its first patient.

There are only a handful of cryopreservation facilities across the globe two in the United States, and one each in Russia, China, Australia and Switzerland. If the claims made on their websites and in the press are accurate, these facilities likely have no more than 600 patients in cryonic storage in total.

Media reports however suggest interest in cryopreservation has risen since the onset of the COVID pandemic, and thousands of people around the world have signed up to be cryopreserved after their death.

So, what is cryopreservation and what are its legal ramifications?

Cryopreservation is the process of using extreme cold to preserve biological material (such as semen, blood and tissue samples) for an extended time. The first living thing to be cryopreserved was a fowl sperm in the 1940s; the first person was cryopreserved in 1967.

To cryopreserve a person, the most important step is a process called vitrification. First, the blood is pumped out of the body. It is replaced with a chemical protectant designed to partially replace the water in the bodys cells with a chemical mixture that prevents the formation of ice (not unlike the antifreeze found in car engines).

The body of the patient is then placed in something akin to a sleeping bag and sealed in a dewar a large vat of liquid nitrogen and maintained at a temperature of -196C until the time for resurrection comes.

The ultimate aim is for the cryopreserved patient to be reanimated at a future time when medical science has advanced sufficiently to cure them of whatever caused their initial death. However, theres no evidence to suggest it will ever happen in the future.

While its proponents describe cryopreservation as a second chance at life, scientists are quick to point out the chances of a successful reanimation are slim.

A person has to be declared legally dead before their body can be cryopreserved, meaning a successful reanimation would truly be a second (legal) life for the revived patient.

It could also be a legal minefield.

Questions that arise include:

are you the same person in your second life as you were in your first, or are you a new legal person entirely?

what happens to the legal obligations you undertook in your first life when you reawaken in your second?

are you still bound by the phone contract you entered into?

do you have to restart your mortgage repayments, and is your property even still your property?

The answer to the last question is likely to be no. A dead person cannot own property so when they die, their estate their money and material possessions is distributed to others according to their will (or, if they die without a will in place, according to the rules of intestacy).

This means, short of radically rewriting our succession laws, if someone is successfully reanimated, none of the wealth or belongings they previously enjoyed will be available to them.

This creates the possibility of cryonic refugees people who wake from cryopreservation in a future time with no social or community ties to rely on and no funds to live off.

In the US, one cryonics facility has attempted to get around this issue by encouraging patients to place their assets in long-term trusts.

A trust is a legal structure whereby Person A becomes the legal owner of a property, but can only use it for the benefit of Person B. There are particular rules about who Person B can be they have to be legally identifiable, for example, and must be able to claim the trust property within a set time period (80 years in many Australian jurisdictions).

In the case of the cryonics trust, Person B is the reanimated patient someone of uncertain legal identity (remember, we dont know if the reanimated patient is the same legal person across their two lives or not) with no guarantee of claiming the trust property within the necessary time period.

These are certainly reasons for lawyers to be sceptical. And of course, even if the trusts are upheld, there is no guarantee the assets they contain will retain their value in an unknown future world.

Even prior to reanimation, however, a cryopreserved patients finances can present legal difficulties.

While the upfront costs of the initial cryopreservation procedure which can come in at more than A$150,000 are often covered by life insurance policies or a one-off payment in a will, the fact that cryonic storage is intended to last for the very long term raises questions about how ongoing bills will be paid far into the future.

There are even historic examples of cryonics facilities threatening to remove patients from suspension unless outstanding storage bills are paid.

Would such an action constitute murder? Can you kill someone who is already dead?

To reach an answer, the law will likely require a test case.

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You can now be frozen after death in Australia. If you get revived in the future, will you still legally be the same person? - The Conversation

Intellia Therapeutics said Sunday that the first 10 patients to receive a CRISPR-based treatment for hereditary angioedema, a genetic disease, saw their swelling attacks the conditions hallmark symptom virtually eliminated for an average of 20 months and counting.

The attacks were reduced by an average of 98%. One patient has remained attack-free for 26 months. Two patients who suffered particularly frequent attacks, experiencing 14 and 16.8 per month, respectively, have now gone more than 20 months since their last attack.

No patient has had an attack in the last 11 months of follow-up, according to the data presented at the European Academy of Allergy and Clinical Immunology Congress. All side effects were either grade 1 or 2 on a 5-grade scale.

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Intellia reports positive results for its CRISPR-based treatment - STAT

The successful development of the revolutionary gene-editing technology called CRISPR won the 2020 Nobel Prize in Chemistry, awarded to Emmanuelle Charpentier of the Max Planck Institute, and Jennifer Doudna of the University of California, Berkeley.

CRISPR offers the exciting possibility of developing new gene therapies treatments involving genome editing to prevent/treat human diseases that have a genomics basis, such as cystic fibrosis, diabetes, muscular dystrophy, sickle-cell anaemia and more. Unfortunately, CRISPR could also be used to achieve bad ends, such as being used in misguided eugenics programmes.

CRISPR stands for clustered regularly interspaced short palindromic repeats, and is a natural molecular technology used by many bacteria to fight off invading viruses. This molecular technology can also be used in mammalian cells to edit genetic DNA by adding, removing or changing DNA letters, and by turning genes on/off without altering their sequence.

Although there are other means of carrying out gene therapy, CRISPR has opened up new possibilities for treating human genetic diseases, is faster and much cheaper than other gene-editing technologies, and has revolutionised biotechnology. Last year the worlds first CRISPR therapy was approved to treat human patients with sickle-cell disease.

Any ideas of modifying the evolution of society through genetic manipulation resonate with the views of Francis Galton (18221911) of guiding human evolution through controlled breeding, also known as eugenics. Not only were Galtons ideas based on false evidence, but they led on to disastrous programmes of mass sterilisation and eventually to the genocidal nightmare of the Nazi gas ovens.

Engineering inheritable genetic changes to produce what might be seen as socially desirable traits that are not disease-related in future generations, such as light skin colour, is problematic

CRISPR should be used to pioneer cures for diseases while upholding human dignity and sanctity of life for all. We must be extremely cautious and conservative about using CRISPR to manipulate the genetic make-up of future generations. Human diversity of cultures, perspectives, abilities and identities are vitally important for global equilibrium and functioning, and we interfere with this diversity at our peril.

A reasonable person might think it would it be a good idea to use CRISPR to eliminate disease-related genes from the human genome, eg genes that predispose people to heart disease, obesity and type 2 diabetes. However, there is mounting evidence that these genes conferred advantages related to survival upon our ancestors prior to the Industrial Revolution, when nutrition was generally poor and patchy (see the views of Maria Esther Rubio Ruiz and others in International Journal of Evolutionary Biology).

[Worlds first gene-editing therapy for humans approved in UK]

Today, many people eat highly processed foods rich in fat/sugar while at the same time leading sedentary lives, a combination that interacts with these old survival-enhancing genes to cause deadly modern diseases. So, in a future world possibly bedevilled by famines and other privations, these bad genes could actually function as good genes. It would be unwise to eliminate them from the population now.

Also, engineering inheritable genetic changes to produce what might be seen as socially desirable traits that are not disease-related in future generations, such as light skin colour, is problematic. Many non-westerners use skin-whitening cream to induce fair complexions, believing fair skin looks better than dark skin. But genetically engineering fair skin in offspring could put them at a future disadvantage in terms of survival. If atmospheric ozone levels deplete significantly, genetically engineered fair-skinned people, who would otherwise be protected by skin melanin, would suffer increased incidence of skin cancer.

A global moratorium on heritable gene-editing was introduced in 2019. This moratorium will end soon

In 2018, maverick Chinese scientist He Jiankui carried out unregulated gene editing of human embryos, two of whom were later born as the twin girls Lulu and Nana. This genetic editing was designed to confer resistance to the Aids-inducing human immunodeficiency virus (HIV) by inactivating the gene CCR5, mimicking a natural mutation that protects a small number of people from HIV.

[ Dodos have been extinct for hundreds of years. Can scientists really bring them back to life?]

This work was greeted with worldwide concern. Scientists pointed out that too little is known about genes to make such changes safely, that other genes can be damaged in the process, and that these changes are passed on to future generations. A global moratorium on heritable gene-editing was introduced in 2019. This moratorium will end soon, and anxieties regarding what CRISPR technology might lead to are mounting.

While CRISPR technology promises wonderful advances in medicine, it also raises profound ethical questions. Going forward, we must remain vigilant in guarding human rights and ethical practices that support equality and dignity of all, regardless of their genetic make-up. No less than the aforementioned Doudna, one of the inventors of CRISPR technology, has called for a ban on heritable gene-editing until scientific, technical and ethical questions are answered and public consensus has developed.

William Reville is an emeritus professor of biochemistry at UCC

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Advantages - and dangers - of new gene-editing technology CRISPR - The Irish Times

Patients

Patients eligible for the study were aged 12 years, weighed 30kg and had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 if aged 18 years34 and Karnofsky or Lansky PS60% if aged 16 years or 12 to <16 years35, respectively (see Supplementary Tables 5 and 6 for details of PS scoring systems). All patients were to receive either peripheral blood or bone marrow allo-HSCT for hematologic malignancy from unrelated donors who were 8 of 8 or 7 of 8 human leukocyte antigen (HLA)-matched (a single allele mismatch at HLA-A, HLA-B and HLA-C, and HLA-DRB1 was permitted). A total of 441 patients were screened for eligibility. After screening, 343 patients were randomly assigned 1:1 to receive vedolizumab (174 patients) or placebo (169 patients) treatment. Randomization was stratified by age (patients aged 18 years or aged 12 to <18 years); HLA match (8 of 8 versus 7 of 8); conditioning regimen intensity (myeloablative conditioning (MAC) versus reduced intensity conditioning (RIC)); and anti-thymocyte globulin (ATG) use (with versus without ATG). Patients received either vedolizumab 300mg or placebo intravenously on day 1 and days +13, +41, +69, +97, +125 and +153 after allo-HSCT in addition to standard GVHD prophylaxis (CNI plus methotrexate or mycophenolate mofetil). Nine patients did not receive study treatment, five were randomized to vedolizumab and four were randomized to placebo treatment.

Of 334 patients who received 1 dose of study treatment (analyzed for safety study end points), 333 also received allo-HSCT (analyzed for efficacy study end points), 168 in the vedolizumab group and 165 in the placebo group. For patients discontinuing the study, reasons for discontinuation included death (26 out of 57 patients in the vedolizumab group and 34 out of 71 in the placebo group), withdrawal by the patient (16 versus 18) and adverse events (AEs; 6 versus 5) (Fig. 1). Median (range) exposure to treatment was 40.0 (18.142.1) weeks for vedolizumab and 39.7 (18.142.3) weeks for placebo. In the vedolizumab group, patients received a mean (s.d.) of 5.4 (2.1) and median (range) 7.0 (17) treatment doses; 52.7% of patients in the vedolizumab group received all seven doses. A mean (s.d.) of 5.1 (2.3) and median (range) 7.0 (17) doses were received in the placebo group; 50.9% of patients in this group received all seven doses. Patient numbers were reduced to 60% of the planned sample size of 558 because of early enrollment termination owing to the impact of COVID-19 on recruitment. Consequently, more patients (n=137, 41.1%) received ATG at baseline than the 25% planned.

Discontinuation of the study refers to all patients who discontinued before the end of the long-term follow-up safety survey period of the study, 6 months after the last dose of study treatment. Withdrawn by physician is noted as reason other. Patients included in the analysis for efficacy end points per protocol were those who received 1 dose of study treatment and also received allo-HSCT. One patient was randomized to receive vedolizumab but did not receive allo-HSCT; per protocol, this patient was not included in the analysis of efficacy end points but was included in the analysis of safety end points.

Patient and transplant characteristics were balanced between treatment groups (Table 1 and Extended Data Table 1). The median age was 55.0 years (range, 1674 years; 1 aged <18 years) and 62.8% were male. The most frequent underlying malignancies were acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and acute lymphoid leukemia (ALL). The conditioning regimen intensity was either MAC (52.4% in the vedolizumab group versus 53.9% in the placebo group) or RIC. GVHD prophylaxis (with or without ATG) was tacrolimus (TAC)+methotrexate (MTX; 42.3% versus 50.3%) or TAC+mycophenolate mofetil (MMF; 3.0% versus 3.0%); cyclosporine (CYS)+MTX (30.4% versus 23.0%) or CYS+MMF (14.3% versus 12.1%). The proportion of patients who received ATG prophylaxis was balanced between treatment groups: 42.3% (n=71) in the vedolizumab group versus 40.0% (n=66) in the placebo group; 57.7% versus 60.0% did not receive ATG.

Neutrophil engraftment occurred in 165 patients in the vedolizumab treatment group and 160 patients in the placebo group. The median (range) time to neutrophil engraftment was 16.0 (835) days in the vedolizumab group and 15.0 (831) days in the placebo group. Platelet engraftment occurred in 159 patients in the vedolizumab group and 148 patients in the placebo group. The median (range) time to platelet engraftment was 18.0 (1136) days in the vedolizumab group and 17.0 (0233) days in the placebo group.

The primary study end point was lower-GI aGVHD-free survival by day +180 after allo-HSCT. There were 24 (14.3%) patients in the vedolizumab group with an event of lower-GI aGVHD or death by day +180 after allo-HSCT compared to 47 (28.5%) patients in the placebo group (Fig. 2a). The frequency of lower-GI aGVHD by maximum clinical stage (see Supplementary Table 1 for a description of clinical staging of aGVHD9) is shown in Fig. 2b for each treatment group, with four cases of stage 24 lower-GI aGVHD in the vedolizumab group compared to 14 cases observed in those who received placebo. The KaplanMeier (KM) estimate for lower-GI aGVHD-free survival by day +180 was 85.5% (95% confidence interval (CI) 79.290.1) for the vedolizumab group and 70.9% (63.277.2) for the placebo group (Fig. 2c). The risk of a lower-GI aGVHD event or death by day +180 after allo-HSCT was 55% less in the vedolizumab group compared to the placebo group (hazard ratio (HR) 0.45, 95% CI 0.270.73; P<0.001). Results were consistent for sensitivity analyses of the primary end point (Table 2), including events occurring within a 7-day time frame at day +187 after allo-HSCT, stratified log-rank tests by randomization stratification factors, analysis with corrected stratification information, competing risk analysis and an analysis excluding aGVHD events graded stage 0 or unknown. By day +180 after allo-HSCT, 23 patients (13.7%) in the vedolizumab group versus 43 (26.1%) in the placebo group had an event of death or lower-GI aGVHD (when aGVHD events graded stage 0 or unknown were excluded) (HR 0.47, 95% CI 0.280.78; P=0.0029). In subgroup analyses of the primary end point (Fig. 2d and Extended Data Fig. 1), HRs consistently favored vedolizumab over placebo regardless of HLA match, conditioning regimen intensity, use of ATG or stem-cell source (bone marrow or peripheral blood). The overall incidence of upper-GI aGVHD, skin aGVHD and aGVHD in the liver by day +180 after allo-HSCT was similar between treatment groups (Supplementary Table 7).

Analysis included all randomized patients who received 1 dose of study treatment and received allo-HSCT. All statistical tests were two-sided. a, Graph shows number and proportion of patients with a lower-GI aGVHD event or death; censored for patients who had not had the lower-GI aGVHD event or died or had the event after a prespecified time, for example, last contact or day +180 after allo-HSCT, whichever occurred first. If a patient had a lower-GI aGVHD event and died due to any cause, including lower-GI aGVHD, the time to event was derived as the time to the first qualifying event (lower-GI aGVHD event). b, Frequency of lower-GI aGVHD by maximum clinical stages 04 by day +180 after allo-HSCT for patients in vedolizumab and placebo treatment groups and also the corresponding frequency of skin aGVHD and liver aGVHD in these treatment groups by maximum clinical stages 04 by day +180 after allo-HSCT. CI was based on the ClopperPearson method. c, KM estimate for the primary study end point lower-GI aGVHD-free survival from first study treatment (day 1) to lower-GI aGVHD event or death due to any cause. Red line shows the vedolizumab group; blue line shows the placebo group; open circles indicate censored patients. HR obtained via a Cox proportional hazards model with treatment group, stratified by randomization stratification factors: HLA match (7 of 8 or 8 of 8), conditioning regimen (MAC or RIC), ATG (with or without) and P value from a log-rank test (P=0.0009). d, Forest plot of prespecified subgroup analyses for the primary study end point of lower-GI aGVHD-free survival by day +180 after allo-HSCT: conditioning regimen MAC or RIC, with or without ATG, CNI TAC or CYS, HLA match, and stem cell source peripheral blood or bone marrow. HRs plotted with 95% CIs were obtained via a Cox proportional hazards model with treatment group stratified by randomization strata. Results for the remaining prespecified subgroup analyses are shown in Extended Data Fig. 1.

The KM estimates for the five key secondary end points analyzed at day +180 after allo-HSCT are shown in Fig. 3.

ae, KM estimates for the secondary efficacy end points. Analyses included all randomized patients who received 1 dose of study treatment and allo-HSCT. In the fixed-sequence hierarchical testing procedure, once 1 efficacy end point was not significant (P0.05), testing of subsequent end points was not performed. P values were obtained using a log-rank test unless otherwise stated. All statistical tests were two-sided. *P value is significant for vedolizumab versus placebo. HR and 95% CI values were obtained from a Cox proportional hazards model with treatment group stratified by randomization strata: HLA match (7 of 8 or 8 of 8), conditioning regimen (MAC or RIC) and ATG (with or without). Time to first documented lower-GI aGVHD, relapse of underlying malignancy or death from any cause. Sensitivity analysis, excluding lower-GI aGVHD events classified as clinical grade 0 or unknown. NRM was a competing risk in this competing risk sensitivity analysis; P value for comparison of vedolizumab with placebo was obtained by a Grays test. Time to first documented IBMTR grade CD aGVHD (any organ) or death from any cause. **Death and relapse were competing risks in this sensitivity analysis; an event was defined as IBMTR grade CD aGVHD (any organ) or death. P value was obtained by a Grays test. Death from first dose of study treatment without occurrence of a relapse. Relapse was a competing risk in this sensitivity analysis; NRM was the time from first study treatment to death without occurrence of a relapse; P value was obtained by a Grays test. Overall survival by day +180 was the analysis of the time from the first dose of study treatment to death from any cause. All deaths were defined as events in this analysis. Time to first documented IBMTR grade BD aGVHD (any organ) or death from any cause. Death and relapse were competing risks in this sensitivity analysis; an event was defined as IBMTR grade BD aGVHD (any organ) or death. P value was obtained by a Grays test.

There was a statistically significant difference favoring vedolizumab over placebo for lower-GI aGVHD-free and relapse of the underlying malignancy-free survival by day +180 after transplant. The KM estimated survival for this end point was 78.9% for the vedolizumab treatment group versus 65.4% for the placebo group. Events of lower-GI aGVHD, relapse or death for this end point occurred in 11, 18 and 6 patients, respectively from the vedolizumab group (total of 35, 20.8%) and 31, 13 and 12 (total of 56, 33.9%) in the placebo group (HR 0.56, 95% CI 0.370.86; P=0.0043). A statistically significant treatment difference favoring vedolizumab for this end point was also maintained after a sensitivity analysis excluding stage 0 and unknown lower-GI aGVHD events (HR 0.59, 95% CI 0.380.91; P=0.0130) (Fig. 3). The secondary end point of IBMTR grade CD aGVHD of any organ-free survival by day +180 (see Supplementary Table 3 for description of aGVHD severity grading using the IBMTR severity index), also demonstrated a statistical difference between vedolizumab and placebo treatment groups. The KM estimated survival for this end point was 78.9% for vedolizumab the treatment group versus 67.7% in the placebo group. Events of grade CD aGVHD of any organ or death counted for this end point occurred in 35 patients (20.8%) receiving vedolizumab versus 52 (31.5%) receiving placebo (HR 0.59, 95% CI 0.390.91; P=0.0204). In a competing risk analysis (death and relapse as competing risks), cumulative incidence of IBMTR grade CD aGVHD by day +180 was lower for the vedolizumab group (13.2%, 95% CI 8.618.8) than the placebo group (21.6%, 95% CI 15.628.2; P=0.0446) (Fig. 3). Secondary end point sensitivity analyses (Supplementary Table 8) and subgroup analyses (Extended Data Fig. 2) showed consistent results with decreased risk in the vedolizumab group compared to the placebo treatment group. The secondary end point of non-relapse mortality (NRM) by day +180 did not meet statistical significance, with 10 patients (6.0%) in the vedolizumab group and 19 (11.5%) in the placebo group (HR 0.48, 95% CI 0.221.04; P=0.0668) dying of non-relapse causes. Following the hierarchical statistical testing procedure, the subsequent fourth and fifth secondary end points were not tested for statistical significance. The KM estimate for the fourth secondary end point of overall survival was 89.7% for the vedolizumab treatment group and 84.4% in the placebo group. All-cause deaths by day +180 counted for this analysis occurred in 17 patients (10.1%) in the vedolizumab group and 25 (15.2%) in the placebo group (HR 0.63, 95% CI 0.341.17; P=0.1458). For the fifth secondary end point of IBMTR grade BD aGVHD of any organ-free survival by day +180, KM estimated survival was 66.4% for the vedolizumab treatment group and 52.3% in the placebo group. Grade BD aGVHD events in any organ counted for this end point occurred in 47 patients (28.0%) in the vedolizumab group and 64 (38.8%) in the placebo group with deaths also counted in 9 and 13 patients in the vedolizumab and placebo groups, respectively (HR 0.64, 95% CI 0.460.91; P=0.0105).

Results for the main exploratory end points at day +180 and day +365 after transplant are summarized (Extended Data Tables 3 and 4). The cumulative incidence of all chronic GVHD events by day +180 was 20.7% (95% CI 14.827.2) in the vedolizumab group versus 21.9% (95% CI 15.828.6) in the placebo group (death and relapse as competing risks; nominal P=0.7555). Chronic GVHD requiring systemic immunosuppression by day +180 occurred in three (1.8%) patients in the vedolizumab group (severity was moderate in two patients and severe in one) and four (2.4%) in the placebo group (one mild, two moderate and one patient had severe chronic GVHD) (Extended Data Table 3). KM estimates for GVHD (any organ)-free and relapse (of the underlying malignancy)-free survival by day +180 were 80.1% in the vedolizumab group and 69.7% in the placebo group; events for this end point occurred in 33 (19.6%) of patients in the vedolizumab group and 49 (29.7%) in the placebo group (HR 0.61, 95% CI 0.390.96; nominal P=0.0243). Events of clinical stage 24 lower-GI aGVHD or death by day +180 occurred in fewer patients in the vedolizumab group (19, 11.3%) than in the placebo group (33, 20.0%) (HR 0.52, 95% CI 0.290.91; nominal P=0.0222). KM estimates for clinical stage 24 lower-GI aGVHD-free survival were 88.5% and 79.5%, respectively. By day +180 grade 24 aGVHD-free survival (per MAGIC criteria10, see Supplementary Table 4) also seemed to favor vedolizumab over placebo; KM estimates were 74.1% for vedolizumab and 63.3% for placebo, with events occurring in 43 (25.6%) and 59 (35.8%) patients, respectively (HR 0.67, 95% CI 0.450.99; nominal P=0.0421). Frequency of lower-GI aGVHD by maximum MAGIC grade were also reported for each treatment group, with corresponding values for maximum MAGIC grade of skin and liver aGVHD (Extended Data Table 2).

Progression-free survival in vedolizumab and placebo treatment groups by day +180 were 83.1% (95% CI 76.588.0) versus 77.6% (95% CI 70.483.3), respectively. Cumulative incidence of all relapse and death events for time to relapse (of the underlying malignancy) by day +180 were similar across treatment groups 10.9% (95% CI 6.716.2) for vedolizumab versus 10.6% (95% CI 6.416.0) for placebo (death as a competing risk; nominal P=0.9090). By day +180, there was no significant difference in relapse of the underlying malignancy between treatment groups, occurring in 18 (10.7%) patients from the vedolizumab group and 17 (10.3%) from the placebo group (HR 1.32, 95% CI 0.513.40; nominal P=0.9821; Extended Data Table 3).

Consistent results were obtained for primary and secondary efficacy end points when these were assessed as exploratory study end points 1 year after allo-HSCT (Extended Data Table 4). By day +365 after allo-HSCT, 21.4% of patients in the vedolizumab group and 33.9% in the placebo group had an event of lower-GI aGVHD or death (HR 0.53, 95% CI 0.350.81; nominal P=0.0041). KM estimates for lower-GI aGVHD-free survival 1 year after transplant were 78.1% for vedolizumab and 65.1% for placebo. Events of IBMTR grade CD aGVHD of any organ or death by day +365 occurred in 47 (28.0%) of patients in the vedolizumab group and 59 (35.8%) of patients in the placebo group (HR 0.68, 95% CI 0.461.00; nominal P=0.0709). Death without relapse occurred in 15 patients (8.9%) in the vedolizumab group and 25 (15.2%) in the placebo group (HR 0.49, 95% CI 0.250.95; nominal P=0.0670). All-cause deaths by day +365 occurred in 28 patients (16.7%) in the vedolizumab group and 36 (21.8%) in the placebo group (HR 0.67, 95% CI 0.411.11; nominal P=0.1741). IBMTR grade BD aGVHD in any organ or death events occurred in 69 patients (41.1%) in the vedolizumab group and 82 (49.7%) in the placebo group (HR 0.71, 95% CI 0.520.99; nominal P=0.0534). Incidence of relapse of the underlying malignancy at day +365 was also comparable between treatment groups occurring in 19.6% of patients in the vedolizumab group versus 13.3% for placebo (HR 2.13, 95% CI 0.974.65; nominal P=0.2097; Extended Data Table 4).

The safety analyses included 334 patients (169 patients in the vedolizumab group and 165 in the placebo group) who received 1 dose of study treatment and were assessed up to 18 weeks after the last dose of study treatment. Median (range) treatment exposure was 280.0 (127295) days for the vedolizumab group (mean (s.d.) of 5.4 (2.05) doses) and 278.0 (127296) days for the placebo group (mean 5.1 (2.25) doses). AEs of grade 3 or higher occurred in 92.3% of patients who received vedolizumab and 89.1% who received placebo (Table 3); the most frequent AEs of grade 3 or higher were anemia (29.6% versus 31.5%); neutropenia (31.4% versus 29.7%); febrile neutropenia (43.8% versus 42.4%); stomatitis (27.2% versus 26.7%); and decreased platelet count (21.9% versus 24.8%). Serious AEs occurred in 120 patients (71.0%) who received vedolizumab and 114 (69.1%) who received placebo (Extended Data Table 5). AEs led to treatment discontinuation in 44 (26.0%) versus 51 patients (30.9%) (Extended Data Table 6).

Table 3 lists serious infections among other AEs (serious and non-serious) prespecified as being of special interest (AESIs) in the study. Occurrence of post-transplant lymphoproliferative disease and Clostridioides infections are also reported in Table 3. AESIs included cytomegalovirus (CMV) colitis, which was reported in one patient from each treatment group (0.6% of patients in vedolizumab group 0.6% in the placebo group). Overall, CMV reactivation was reported in 23.7% of patients in the vedolizumab group and 18.2% in the placebo group. Most of the CMV reactivation events were grade 1 to grade 2 and none was above grade 3. The proportions of patients with grade 3 CMV reactivation were similar in both treatment groups. CMV infections were analyzed in subgroups of patients who received ATG prophylaxis or not (Supplementary Table 9). For those receiving ATG, grade 3 CMV infections occurred in seven patients (4.1%) in the vedolizumab group and six patients (3.6%) in the placebo group and serious CMV infections in seven (4.1%) versus three patients (1.8%), respectively. For patients treated without ATG, the frequency of grade 3 CMV infections was numerically lower in vedolizumab-treated versus placebo-treated patients (1 (0.6%) versus 3 (1.8%), respectively), one patient in the vedolizumab treatment group had a serious CMV infection. Other serious infections (excluding CMV colitis) occurred in 125 (74.0%) of patients receiving vedolizumab versus 111 (67.3%) receiving placebo. These are listed by infection type (Extended Data Table 7). The most common serious infections were CMV reactivation (23.7% versus 18.2%); pneumonia (7.7% versus 8.5%); sepsis (5.3% versus 7.3%); and bacteremia (4.7% versus 5.5%) (Table 3). Serious abdominal and GI infections occurred in eight patients receiving vedolizumab (4.7%) and three receiving placebo (1.8%). Clostridioides infections occurred in 14 (8.3%) patients in the vedolizumab treatment group and six (3.6%) patients in placebo treatment group; of these 2.4% of patients in each treatment group had Clostridioides colitis (C.difficile colitis or Clostridioides colitis). For safety end points, statistical analyses were not adequately powered for comparisons between treatment groups. There were five patients with an AE of human polyomavirus infection; none of these was diagnosed as progressive multifocal leukoencephalopathy (PML). One patient with AML relapse and subsequent additional therapy developed PML, with a fatal outcome ~6 months after the last dose of vedolizumab. An independent adjudication committee deemed the most probable cause of this event to be the immunosuppressive treatment for AML. Secondary malignancies occurred in seven patients (4.1%) in the vedolizumab group and 16 (9.7%) in the placebo group. Post-transplant lymphoproliferative disease occurred in three patients (1.8%) in the placebo group only (Table 3).

Overall, 48 patients died during the period from first dose of study treatment to 18 weeks after last dose: 21 (12.4%) in the vedolizumab group and 27 (16.4%) in the placebo group. Leading causes of death were multiple organ dysfunction syndrome (3.0% versus 1.8%); AML recurrence (0.6% versus 2.4%); respiratory failure (1.8% versus 1.2%); pneumonia (1.2% versus 1.2%); and sepsis (0.0% versus 1.8%). Intestinal aGVHD was listed as cause of death in 0.0% versus 1.2% patients, aGVHD in liver (0.6% versus 0.6%) and aGVHD (0.6% versus 0.0%). An additional 17 patients died during the period from 18 weeks post-treatment to 12 months after HSCT: eight in the vedolizumab group and nine in the placebo group (Extended Data Table 8).

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Dr. Dave goes on to explain its important to understand genetic therapies are not just for genetic ALS. We can use gene therapy to go after sporadic ALS because we know that there are certain proteins that are involved in 90% of ALS. And if we can go after those proteins using gene therapy approaches, we can now go and treat all ALS, and not just a particular genetic subtype. And that's the future of gene therapy. How can we use gene therapy to go after the sporadic forms of ALS?

More genetic testing and counseling will help identify more people living with the disease who could benefit from gene therapies; people like Larry Falivena.

In August 2017, Larry heard those three terrible words: You have ALS. Like most who experience the lengthy diagnosis process, Larry suspected that was the case, but actually, hearing it from his doctor was devastating. A husband and father of two young boys, he had so many plans for the future, or so he thought.

After his diagnosis, Larry was encouraged to get a genetic test even though he had no known family history of ALS, and he says making that decision changed the course of his diseaseand his life. Sure enough, aSOD1mutation was found, a known genetic cause for the disease.

Larry was able to get into an ongoing clinical trial for a treatment of SOD1-ALS called tofersen, now known as Qalsody.

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Let's See More Genetic Testing and Counseling - ALS Association

Three years after 23andMe completed a dizzying IPO at a valuation of $3.5 billion, the genetic testing company is considering going private again. As is typical for SPAC IPOs, the company enjoyed a peak market value of $6 billion shortly after the IPO, but has since seen a continuous decline and is currently trading below $300 million. How is it that a company that raised over a billion dollars, once boasted famous investors like Richard Branson and was named "Invention of the Year" by Time Magazine, is today traded at such a low value? The reasons were actually predictable.

Recently, CEO Anne Wojcicki announced that the company plans to purchase all existing shares and make it private again. Wojcicki herself owns 20% of company shares, which she has received over the years as part of her compensation policy. Anne is the sister of Susan Wojcicki, the former CEO of YouTube, and the ex-wife of Sergey Brin, one of the founders of Google. Brin and Google were early investors in 23andMe and one of the reasons for its great success in the beginning.

Since it was established in 2006 and until today, the company has raised $1.8 billion, while it has never recorded a profit. 2023 was a particularly terrible year and included three rounds of layoffs, with sales of approximately $300 million - a 32% drop compared to 2019 - and a record loss of $312 million. In a conversation with investors, Wojcicki attributed the loss to a drop in sales of genetic testing kits, as well as a drop in research revenue after ending her main collaboration with the pharmaceutical giant GSK, with which she had a controversial agreement to share genetic information that she had collected on her clients. The complex financial situation and the lack of new channels for raising capital have now led Wojcicki to a last resort - to take the company private in order to bring in new investors.

Celebrities held "spit parties"

Wojcicki founded the company with geneticist Linda Avey who came up with the idea, and who she pushed out three years later, maintaining exclusive control ever since. For a period of time the company was a great success and for good reasons - the product was interesting and made genetic tests accessible to the general public for the first time, something which used to be the domain of medicine and law enforcement. Suddenly, with a little saliva, anyone who wanted to could gain new insights about their ancestry, and even locate relatives they never knew existed. Celebrities held "spit parties," and Wojcicki gained both fame and the admiration of Silicon Valley as an innovative entrepreneur.

But the same problem has always hovered over the company's activity: a genetic test is only conducted once, so if this is the core of the company's activity, the ability to grow is very limited, even more so if you happen to have a competitor or two (such as Ancestry and the Israeli MyHeritage). As a result, this led to the inevitable and desperate search for complementary products, but how much more can a home DNA testing business expand? It turns out, not much, and in any case, what was offered was not a business model that could prosper. Among other things, a genetic test for dogs was developed (Because who doesn't want to know the genetic makeup of their mixed dog?) and family tree building services. Even if these are compelling offers, how many times can you do it?

Additionally, since 2019 the public has understood that these companies do as they please with their customers most sensitive data, including selling their genetic information to pharmaceutical companies for research. This has understandably caused the public to be suspicious of genetic testing companies, especially 23andMe. This concern has proved to be justified; not only have these databases been used by law enforcement to solve crimes, but data leaks and hacks happened more than once. The most recent hack took place on October 6, when 23andMe servers were hacked and the genetic information of a million users - mostly Ashkenazi Jews - were stolen.

23andMe then tried to develop into another equally complex field: pharmaceuticals. They sought to develop and market new drugs based on research on the genetic samples theyd collected over the years and whose owners consented to the use of their samples for research purposes (13 million samples). But drug development is an expensive, slow and rather risky business, and the company was unable to introduce new sources of income quickly enough. Accordingly, the stock plummeted by 98% in the last three years.

Alongside drug developments, the company tried to develop complementary health services based on "polygenic scores. These grades are taken from crossing the list of known genetic variations with the genetic information of any person, and their purpose is to reflect the tendency of that person to any disease. 23andMe has published over 30 such scores for illnesses such as depression, PTSD and bipolar disorder. However, experts in the field including geneticists and psychiatrists believe this to be an immature science. Because the scores do not weigh other contributing factors, experts say that they are not useful and can lead to unfounded panic.

Researchers were actually so alarmed by the popular polygenic grading service that 23andMe developed that they appealed to the FDA demanding that such grades be banned, fearing that such data could lead to life-threatening psychological stress. Of course, this did not prevent the company from launching in November a product for subscribers that offers genetics-based medical treatment called Total Health and costs approximately $1,200 per year. At the same time, the company went through a series of layoffs and was hit with about 30 class action lawsuits surrounding the massive data breaches it experienced.

The challenge: to restore consumer trust

For 23andMe, the solution to the embarrassing situation is quite clear: it needs to restore consumer trust and make them believe that they can use their genetics-based medicine services (as a subscription program). The company must also identify new research partners and, above all, find the investors who are up for an adventure with a company that is losing profit and whose chief product can only be used once.

23andMes situation reveals quite a bit about the changing world and their failure to adapt to it. Public skepticism and ethical concerns regarding user data is enormous. Customers have become less interested in a few hundred dollars to give their genetic data to a company, only for this data to be sold to third parties or to make themselves vulnerable to abuse either by hackers or by government agencies for policing. Prospective 23andMe customers today need to consider whether the promise of bridging medical disparities is worth the potential insecurity. Under these current conditions, the future of 23andMe seems nothing short of impossible.

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23andMes promise of genetic testing has been shattered - CTech

Introduction

The global genetic testing market was valued at USD 15.9 billion in 2022 and is expected to reach USD 39.2 billion by 2032, growing at a CAGR of 9.7% from 2023 to 2032. This growth is driven by the increasing prevalence of genetic disorders, rising demand for personalized medicine, and advancements in genetic testing technologies, such as the adoption of next-generation sequencing (NGS) which is anticipated to grow at a CAGR of 22.8%.

Key growth factors include the rising incidence of cancer and other genetic diseases, necessitating early diagnosis and intervention. Due to heightened awareness and the push for early detection of genetic anomalies, the adoption of genetic testing in prenatal and newborn screening is also increasing. The prenatal and newborn testing segment dominated the market in 2022, reflecting the increasing focus on early genetic diagnosis.

Despite these growth drivers, the market faces significant challenges. The high cost of genetic testing, which can range from under USD 100 to over USD 2,000 depending on the complexity of the test, remains a major barrier to widespread adoption. Additionally, regulatory hurdles and data privacy concerns further impede market growth. Stringent regulatory requirements slow down the introduction of new tests, while fears of genetic discrimination and unauthorized data access deter potential users.

Recent developments in the genetic testing market include significant mergers, acquisitions, and funding activities that are shaping the industry. For instance, Labcorps aggressive M&A strategy includes a USD 239 million acquisition of Invitaes assets, expanding its presence in oncology and rare diseases. This follows Labcorps USD 237 million purchase of BioReference Healths clinical diagnostics and womens health business, expected to generate USD 100 million in annual revenue. Veracyte also acquired C2i Genomics for up to USD 95 million, enhancing its cancer diagnostics capabilities.

Additionally, Gilead Sciences secured USD 210 million in funding from Abingworth to advance its antibody-drug conjugate, Trodelvy, for non-small cell lung cancer. These activities reflect a dynamic market focused on expanding capabilities and leveraging strategic partnerships to drive growth and innovation.

In conclusion, the genetic testing market is poised for substantial growth, fueled by technological advancements and increasing awareness of genetic disorders. However, addressing cost and regulatory challenges will be crucial to realizing this potential. The markets trajectory underscores the importance of innovation and strategic collaboration in overcoming these barriers and expanding the accessibility and efficacy of genetic testing globally.

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Genetic Testing Market To Hit USD ~39 Billion by 2032 - Market.us Media - United States Market News

Former U.S. Rep. Mayra Flores wants mandatory DNA testing of all immigrants and favors a return of the much-denounced policy of separating children from their parents at the border.

The Donald Trump administration utilized both practices and likely would resume them if he is elected in November; Trump has said he plans to resurrect all of his previous immigration policies and impose new ones that would be more severe, including the largest domestic deportation operation in Americas history.

Flores, who is running to regain the congressional seat she lost in 2022, defends those policies, although family separation has roundly been denounced as inhumane. Some of the children were mere infants. Worse, many of those children have not been reunited with their parents half a decade later.

Until recently, our stated immigration policy was to keep families together. Federal law prohibits keeping immigrant children in detention for more than 20 days. The Trump administration bypassed that law by reclassifying separated children as unaccompanied minors in order to detain them indefinitely.

Obviously the law was violated in spirit and it doesnt seem to matter to Flores, who seeks to return to Congress to enact such laws. In fact, Republican lawmakers have filed legislation that would mandate genetic testing of immigrants. Our own Sen. Ted Cruz submitted the bill in that chamber.

I dont care if these children are with us for months, she said at a February gathering of the conservative youth group Turning Point USA in Brownsville.

Flores said longer child detentions might be necessary to allow time for the DNA testing, which she says is needed to verify that the children in fact are related to the people who brought them.

Genetic testing shouldnt be needed for such evaluations; it shouldnt be hard to see a difference in a childs comportment with a parent or guardian as opposed to a total stranger.

Its also obvious that any DNA testing that was done in the past didnt work. Thousands of families remain separated and might never be reunited; records of those tests and related detentions if kept at all were so shoddy that officials continue looking for detained childrens parents and cant find them.

Moreover, laboratories across the country that would perform such tests would have difficulty handling the burden not to mention the expense. Labs currently are so backlogged with forensic testing that criminal cases are being delayed while they wait for evidence.

Widespread testing during the Trump term was slowed down further because the demand for the tests outpaced the supply. Trump and his supporters constantly throw out the term family values in their campaigns. Shredding families, regardless of their nationality or legal status, obviously clashes.

Keeping migrant families together isnt just the right thing to do, it seems the most practical and efficient. Processing them together should speed up the process and ensure that they receive visas together if they qualify, or are deported together if they dont.

Republicans penchant for punitive measures increasingly is defying not only practicality, but morality.

The following editorial published in AIM Media Texas on May 29:

Follow this link:
DNA testing of immigrants more trouble than it's worth - Victoria Advocate

By Olivia Trani

Women are twice as likely as men to develop post-traumatic stress disorder, but the factors contributing to this disparity have largely remained unsettled. A research team led by Virginia Commonwealth University and Lund University in Sweden conducted the largest twin-sibling study of PTSD to date to shed light on how genetics may play a role. Their results, published Tuesday in theAmerican Journal of Psychiatry, are the first to demonstrate that women have a higher genetic risk for the disorder compared with men.

By analyzing health data from over 16,000 twin pairs and 376,000 sibling pairs, the research team discovered that heritability for PTSD was 7 percentage points higher in women (35.4%) than in men (28.6%). They also found evidence that the genes that make up the heritable risk for PTSD vary between the two sexes.

The researchers say their findings could inform strategies for PTSD prevention and intervention following a traumatic event, as well as help address stigmas related to womens mental health.

Women are at higher risk for developing PTSD than men, even when controlling for the type of trauma, income level, social support and other environmental factors. Some of the theories as to why that is have frankly been unkind to women, such as attributing the sex difference to a weakness or lack of ability to cope, saidAnanda B. Amstadter, Ph.D., a professor in theVCU School of Medicinesdepartments ofPsychiatryandHuman and Molecular Geneticsand lead author of the study. I think this study can help move the narrative that people can have an inherited biological risk for PTSD, and that this genetic risk is greater in women.

Nearly 70% of the global population are exposed to at least one traumatic event in their lifetime, such as physical or sexual assault, a motor vehicle accident, exposure to combat or a natural disaster. About 6% of those who are exposed to trauma develop PTSD.Amstadters research focuses on understanding the conditions that might increase or decrease a persons risk of experiencing PTSD, particularly how a persons genes impact their risk.

If you think of risk for PTSD like a pie chart, were trying to better understand what factors make up the pieces of this pie, she said. Some of the risk is influenced by a persons environment, such as the experiences they have while growing up. On the other hand, some of the risk will be influenced by the genes they inherit from their parents.

Previous research has looked into how genes influence the likelihood of developing PTSD, but the study conducted by Amstadter and her colleagues is the first of its kind to investigate how genetic risk varies by sex.

For this project, the research team examined anonymized clinical data from Swedish population-based registries. Their analysis consisted of more than 400,000 pairs of twins or siblings born up to two years apart in Sweden between 1955 and 1980. Studies on twins and siblings, because of their genetic similarities, can help researchers determine how a persons genes influence their risk for mental illnesses.

Every time a person within this age group interacts with Swedens health care system, whether thats visiting their primary care doctor, filling a prescription or going to the hospital, that information is recorded in their national registries. This kind of data is a really powerful tool for addressing questions related to genetic risk for medical conditions, Amstadter said. Prior PTSD studies involving twins and siblings have typically only included a few thousand individuals. Because our sample size was so large in comparison, we were able to make calculations with a higher degree of certainty.

Through statistical modeling, the researchers calculated how much a persons genetic makeup influenced their likelihood of developing PTSD following a traumatic event. In finding that PTSD was 35.4% heritable in women but only 28.6% heritable in men, they demonstrated that women have a higher biological risk for PTSD.

Their models also revealed that the genes associated with PTSD were highly correlated (0.81) but not entirely the same between men and women. This suggests that the genetic underpinnings of sex hormones, like testosterone, estrogen and progesterone, may be involved in the development of PTSD. The research team is collaborating with the Psychiatric Genomics Consortium to identify the molecular genetic variants that may contribute to sex-specific pathways of risk.

Amstadter conducted the research at theVirginia Institute for Psychiatric and Behavioral Geneticsat VCU alongside co-authors Shannon Cusack, Ph.D., a postdoctoral scholar; and Kenneth Kendler, M.D., the institutes director, professor of psychiatry and eminent scholar. They collaborated with Lund University co-authors Sara Lnn, Ph.D.; Jan Sundquist, M.D., Ph.D.; and Kristina Sundquist, M.D., Ph.D.

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Women have a higher genetic risk for PTSD, according to study by VCU and Swedish researchers - VCU News

The news cycle is consistently filled with articles about gender, sex, male, and female, in addition to a whole new dictionary of terms like nonbinary, two-spirit, cis-gender, pansexual, and so on. Our culture is obsessed with the idea of so-called sexual or gender identity. Rather than embracing Gods purposeful and unique design of male and female, they have exchanged the truth of God for a lie and worship the creature rather than the Creator (Romans 1:25). The alphabet mafia chooses to ignore Gods definitions and to redefine (or in many cases not define!) what it means to be male and female. They see the key to equality is for there to be NO differences between the sexes. In their view, we all just need to be the same.

We see examples of this in stores where clothing is no longer designated as mens OR womens and toys are no longer boys OR girls. We see it in sports where biological men are allowed to compete against biological women because the men identify as women. Courts are ruling that the male-only military draft may not be constitutional. A lawyer representing the National Coalition of Men said, Either they need to get rid of the draft registration or they need to require women to do the same thing that men do.1 At the 2023 American Anthropological Association (AAA) conference, a session about skeletal differences between males and females was canceled because it was considered transphobic. The AAA stated, There is no single biological standard by which all humans can be reliably sorted into a binary male/female sex classification.2 As a PhD geneticist, I can confidently say this is scientifically absurd, and as a Christian, I can say its biblically wrong as well.

God created males and females equalbut different. Thats not to say we dont have some sameness. We both bear the image of God (Genesis 1:2627). We both are sinners in need of salvation (Romans 3:23), and when we receive Christ as our Savior, we are one in Jesus (Galatians 3:28). But we are also different!

Women and men are both made in the image of God, but we have unique character qualities that cause us to bear that image differently. Elisabeth Elliot eloquently said, These two people [Adam and Eve] together represent the image of Godone of them in a special way the initiator, the other the responder. Neither the one nor the other was adequate alone to bear the divine image.3

Women tend to be caring and nurturing. God displays this characteristic vividly in Matthew 23:37, where Jesus speaking of the Israelites says, How often would I have gathered your children together as a hen gathers her brood under her wings. Men tend to be protectors and fight to protect those in their care. God displays this characteristic in Isaiah 42:13 where Isaiah says, The Lord goes out like a mighty man, like a man of war he stirs up his zeal; . . . he shows himself mighty against his foes. Women and men bear Gods image differently and that is part of Gods good design. We are equal but different. Im not saying that certain character qualities of God are exclusive to one sex or the other, but we tend to see certain characteristics more often or more clearly in one sex than the other, and that is good!

Men and women also have different functions and roles especially within marriage and the church. God created Eve as a helper to Adam (Genesis 2:18), and wives are to submit to their husbands (Ephesians 5:22). This doesnt imply an inferior/superior relationship within marriage; rather, it reflects different roles. We see this reflected in the Trinity as Jesus submits to the Father yet is equal to the Father. Husbands are to love their wives as their own bodies and as Christ loved the church by dying for her (Ephesians 5:2528). These different roles are an earthly reflection of the heavenly reality of the relationship between Christ and the church (Ephesians 5:32). Again, men and women are equal but different, and that is good!

Men and women are also biologically unique, and sometimes, we can even see directly how that biological design is related to our different character qualities and functions/roles. Gods design is truly purposeful! In this article, well explore some of the genetic and cellular differences between men and women.

Contrary to what the AAA said, there IS a single biological standard by which all humans can be reliably sorted into a binary male/female sex classification. Its called our sex chromosomes. Females have two X chromosomes, and males have one X and one Y chromosome. I have an easy saying to help people remember this: No Y, no guy! The Y chromosome has the sex-determining region Y gene (SRY for short) that inhibits female anatomical growth and induces the formation of male anatomy during embryo development. Some will argue there are sex chromosome abnormalities that make sex determination at birth or even puberty challenging. While these abnormalities are real in our fallen world (and these parents and children need compassion and support), it is never right to argue for normal from the abnormal.

Many of the genes on the Y chromosome (like SRY) are unique and dont have any match on the X chromosome. But there are some genes for basic cellular functions that exist on both the X and Y. Genes for basic cellular functions usually do not differ much within the human population because these are functions that all human cells must perform for people to live. However, scientists have discovered a gene, named RPS4, that has different versions on the X and Y chromosomes.4 This gene has the instructions for a ribosomal protein, and ribosomes assemble proteins in our cells. This means that male and female ribosomes are different. This blew my mind! The biological classification of mammals, which includes humans, dont really differ much in their ribosome makeup, yet God has seen fit to design male and female humans with different ribosomes. Why? I have no idea! Im excited to see more research that determines why this difference is important.

Although females have two X chromosomes, one of them is inactivated. Males only have one X chromosome and females in essence only have one active X chromosomeor so we thought. It turns out that 1523% of the genes on the so-called inactive X may still be active in that proteins are made from the genes.5 Many of those genes are thought to be related to the immune system, and as a result, women may have a more robust immune system. Women have higher circulating numbers of white blood cells and nearly every immune system response in females is higher.6 This relates well to a womans function/role in caring for children who often harbor a lot of germs! Also, women tend to have the character quality of being social and being in groups of people more often than men.b The gene activity on the inactive X may offer a protective mechanism against exposure to harmful bacteria and viruses often found in these social interactions. It also may mean that man flu is a real thing!

A 2017 gene activity study looked at 18,000 genes in 45 tissues to see if there were differences in activity between males and females.7 The researchers expected only a few hundred of these genes would show a difference. However, they found a whopping 6,500 genes (1/3 of those studied) have different activity levels!8 Some genes are active in men or women only, while some are much more active in one sex or the other. Much of the difference in activity levels is thought to relate to sex hormone differences. Testosterone in males and estrogen/progesterone in females likely causes genes to be read differently, resulting in different outcomes. One journalist in discussing these differences said, True equality is about respecting difference, not trying to erase it . . . . To be equal, men and women dont have to be the same. Which is just as well, because theyre not.9 Equality of the sexes should not, does not, and cannot mean sameness on a biological (or biblical) level. Thinking otherwise can have dangerous repercussions.

Differences in male/female genetics and their outcomes play a significant role in disease development, diagnosis, and treatment. For example, in males, fatty deposits in coronary arteries tend to be at specific locations, whereas in females, the deposits tend to line the artery more evenly, which makes heart disease harder to detect in females.10 Often, women are not included in clinical trials for the study and treatment of disease. This may explain why drugs that are effective at treating disease in men sometimes do not work in women. Its very likely that men and women metabolize drugs differently (because of sex chromosome and sex hormone differences), and what is an effective treatment in one sex may not be in the other.

Dr. Paula Johnson, founder and former executive director of the Connors Center for Womens Health and Gender Biology, stated, Today, we know that every cell has a sex. . . . And what it means is that men and women are different down to the cellular and molecular level. It means that were different across all of our organs, from our brains to our hearts, our lungs, our joints.11 Yes and amen! In part 1, weve learned some of many, many genetic and cellular differences between males and females. In part 2, well delve into the anatomical and physiological differences to understand more about how Gods unique biological designs of men and women relate to their character qualities and functions/roles. It truly is purposeful design!

More:
Men and Women's Different Biology Supports Their Different Roles - Answers In Genesis

The National Nuclear Regulator (NNR) has started with another round of hearings on June 3, owing to concerns about the last consultation process having been insufficient.

The regulator conceded that the public required more information, but only after civil society organisations such as Southern African Faith Communities Environment Institute (Safcei) voiced its dissatisfaction with the overall governance and public participation process for the Koeberg long-term operation (LTO), or lifetime extension.

Other organisations that also raised the same concerns include Project90by2030, Save Bantamsklip, Earthlife Africa Johannesburg and Koeberg Alert Alliance (KAA).

Safcei executive director Francesca de Gasparis lists one of the main issues as being that the NNR held public hearings before the actual release of essential documentation, including a latest seismic risk study.

She says issues of safety are integral to determining the safety of the LTO, especially as the last scientific study to assess seismic risk was done in 1976.

The public needs to have sufficient data and time to make meaningful submissions. The safety of the LTO of Koeberg is a compliance and governance issue that cannot be taken lightly, De Gasparis states, questioning why South Africans have to accept 20 more years of a nuclear power station that would get ten years at most in France.

The organisations and members of the public have also raised concern about a number of safety recommendations made by the International Atomic Energy Agency (IAEA) that have not been implemented at Koeberg or, if implemented, have not been shared with the public.

These recommendations include a complete revalidation of the qualification of cables in the containment building, the full functionality of the containment structures monitoring system, the revalidation of time-limited ageing analyses and aging management of the structures, systems and components.

Failure to provide confirmation that these issues have been duly addressed has left no room for meaningful engagement. The containment structures storing high level waste are still cracked, one of which was a 110 m crack back in 2022 and aging management plans have not been shared with the public, Safcei says.

Additionally, Safcei says, an emergency compliance drill conducted at Koeberg in November 2022 revealed 22 noncompliance issues, including that the Mass Care Centre at the plant is not suitable to accept and respond to accident victims that have been exposed to radioactive areas.

KAA says Eskom has not been forthcoming about how it has addressed the critical safety issues highlighted by the IAEA regarding the LTO.

At first, Eskom did not want to make a safety case report available, then they released a heavily redacted version. After much pressure, the safety case is now available, but the 289 supporting documents are unavailable to the public. Why the secrecy, KAA member Lydia Petersen asks.

Earthlife Africa representative Makoma Lekalakala says extending Koebergs lifespan also means more toxic waste, hence the need for expanded disposal facilities on site and at Vaalputs in the Northern Cape, which stores low-level waste materials.

She adds that no feasibility studies provided to the public have shown that such expansions are doable, especially considering the proximity to local communities.

The conditions of the infrastructure to extend the life of the plant, in addition to the environmental and climate impacts, all affect the people and the planet, Lekalakala notes.

Project90 member Gabriel Klaasen agrees, saying Koeberg is already storing 40 years worth of high-level radioactive nuclear waste, for which there is no permanent solution. Once a week a truck containing low-level nuclear waste travels along the R355 alongside other motorists, with four accidents having occurred with these types of trucks over the years.

If we do not have a solution for the existing waste, why would we extend Koeberg and add an additional 20 years of waste to the mess?

De Gasparis concludes that not only is it unclear whether the plant is safe, but people have to accept that this plant will operate for another 20 years when there is much risk involved. If Eskom has addressed issues sufficiently, she implores the utility to provide proof of that.

ESKOM RATIONALE

The Koeberg nuclear power station, located 30 km north of Cape Town, is reaching the end of its 40-year designed lifespan, and Eskom has submitted its safety case to the NNR to extend the plants life by another 20 years.

Koebergs 1.8 GW generation potential is a key part of Eskoms ability to provide sufficient power to the country.

Unless the NNR grants Eskom a 20-year extension on Koebergs operating licence, the plants two 900 MW reactors will have to shut down in July this year.

Despite having taken the decision to apply for an LTO extension in 2010, the programme has been massively delayed and Eskom is now rushing to make the July 21 deadline.

Eskom says the cost of a nuclear plant LTO project is significantly cheaper than adding new onshore wind or solar PV. The primary energy cost of Koeberg is 99c/kWh, compared with 49c/kWh for wind and 43c/kWh for solar PV.

Eskom also maintains that nuclear is one of the lowest carbon emission sources of energy in the country and that the waste produced during the LTO of Koeberg would be moved to an off-site storage facility to be developed by the National Radioactive Waste Disposal Institute.

The Koeberg plant, despite having older infrastructure, which Eskom says does not necessarily mean the plant becomes less reliable or stable, lends stability to the national grid and has provided reliable baseload power to the national grid for many years.

By performing comprehensive safety assessments and applying good asset management practices, nuclear power plants can achieve safe plant operation for more than 60 years, Eskom states.

Read more here:
NNR hosts new round of talks with public over Koeberg's life extension - Creamer Media's Engineering News

From Philly and the Pa. suburbs to South Jersey and Delaware, what would you like WHYY News to cover? Let us know!

Within the last decade, cell and gene therapy research and manufacturing have produced new options and hope for people with cancer, inherited or rare disorders, and chronic illnesses that may otherwise be fatal or severely debilitating.

The field is still in its infancy, but scientists are optimistic that these new therapeutics will lead to major advancements in how health care providers can treat, prevent or cure disease.

And a growing number of cell and gene therapies companies and experts doing this kind of work are calling Philadelphia home, according to a new report by the Chamber of Commerce for Greater Philadelphia.

Claire Greenwood, chamber senior vice president of economic competitiveness, said over time, this could make the region a top hub for innovative research and breakthroughs, and make it a major competitor with markets in Boston and San Francisco.

I think what weve seen and what well continue to see is when our institutions invest in really cutting-edge science, if we bring all the other pieces together, were going to see advantages around how that allows us to compete, Greenwood said.

Read more:
Philadelphia cell and gene therapy industry sees rapid growth - WHYY

The PlasmidFactory GmbH was founded in 2000 in Bielefeld/Germany, with four employees. In the meantime, under the leadership of the Founder and Managing Director , Dr Martin Schleef, the company has become a well-known contract manufacturer (CDMO) for plasmid and minicircle DNA. Today, PlasmidFactory has 50 highly qualified employees. For more than four years now, the company has been working at full speed and on an extraordinary scale - in addition to scientific research and optimisation of production especially for production of mRNA vaccines. Dr Schleef shares his insights about PlasmidFactory and his rich experience in developing life-saving products.

You have been working in plasmid research and production for more than 30 years and have played a crucial part in contributing to the development of the COVID-19 mRNA vaccine. How did this come about?

PlasmidFactory specialises in producing DNA of extraordinarily high purity for gene therapy and genetic vaccine research. We are an established supplier to biotechnology and pharmaceutical companies as well as to universities and research institutes worldwide. We are well-known within the industry. All manufacturing, research and development is concentrated at the Bielefeld site in Germany. Our manufacturing processes for plasmid DNA are ideally suited for producing mRNA vaccines based on it.

Was the rapid growth in demand for mRNA for vaccines surprising?

Not really. Plasmids have been used as starting materials for manufacturing viral vectors (AAV, Lenti, etc.), and for producing RNA for quite some time. In particular, the production of plasmid DNA as a starting material to produce RNA cancer therapeutics and vaccines has become very important, especially against the background of the COVID-19. RNA is considered a promising vaccine candidate for the prevention of certain viral infections. It has the advantage of neither integrating into the genome of the cell nor remaining in the long term as a potentially effective active molecule in a patient's body. Besides protection against COVID-19, recently developed mRNA-based vaccines have been tested for their protection against influenza virus, Zika virus, cytomegalovirus, and many others. In addition, various mRNA vaccines are currently being tested for their tolerability when used as combination vaccination. So, as you can see, the current applications for mRNA are not yet exhaustive, and we look forward to continuing to play an essential role in the value chain.

Large-scale manufacturing and production in the highest purity grades of plasmid and minicircle DNA as a starting material for RNA vaccines has gained importance. How did you ensure that PlasmidFactory can handle both parameters simultaneously?

We have been working in this area for several years and are constantly optimising it. Even before COVID-19, we significantly expanded our capacity in 2020 to meet the orders of our national and international customers. In the summer of 2020, the concept for the laboratory expansion was finalised. We received funding from the NRW state government and have been able to produce on a multi-gram scale in High Quality Grade to support the COVID-19 vaccine industry.

Moreover, investments have been made to implement the manufacturing of DNA in full GMP Grade. The newly built GMP facility is also located in Bielefeld and will be up and running by the end of summer 2024. This will enable us to provide our global customers not only with High Quality Grade but also with GMP Grade plasmid and minicircle DNA on a large scale.

You mentioned the term "High Quality Grade". Is it your creation, and what exactly does it mean? How does it differ from GMP Grade?

Yes, initially, it is, but it denotes "high quality", so the term is now also used by other manufacturers.

Our "High Quality Grade" plasmid DNA was established over 15 years ago based on the EMA guidelines CHMP/BWP/2458/03, CPMP/BWP/3088/99, and, since 2021, on EMA/246400/2021 for highest quality requirements. For product safety reasons, the manufacturing process avoids using substances of animal origin throughout the entire production chain. It guarantees the highest possible product purity through reliable separation of impurities, e.g., bacterial chromosomal DNA or damaged plasmids. To prevent further contamination, only one plasmid is produced at a time in the facility used exclusively for High Quality (HQ) Grade plasmids; no parallel plasmid productions occur in the same facility.

The HQ fermentation is physically separated from the purification (chromatography) to ensure that downstream processing of the sensitive DNA is not affected by live contaminants.

Actually, HQ Grade products are already being used in clinical trials studies. However, GMP Grade goes one step further by exclusively using single-use equipment and complying with applicable GMP guidelines, and it is, of course, GMP certified. This is a stand-alone trait and signifies another important step in PlasmidFactorys goal to further extend the lead over the competition.

What unique expertise do you have in this field?

The proprietary, unique purification process is one of our unrivalled advantages. It results in a high grade of pure, supercoiled (ccc) plasmid monomers that meet regulatory requirements to form a defined, homogeneous product, which undergoes a series of cell bank and plasmid DNA product quality control checks before release.

High-quality Grade Plasmid DNA is produced based on a cell bank (RCB) created at PlasmidFactory and the uniquely effective proprietary ccc Grade DNA technology. For both the cell bank and the plasmid DNA product, PlasmidFactory offers a wide range of quality controls, so a product is ultimately created that is tailor-made for the respective application or as per the corresponding regulatory requirements.

For example, our High Quality Grade Plasmid DNA is used in the GMP-compliant production of recombinant viruses, antibodies and RNA for clinical trials.

Our products and processes are continuously and precisely optimised and, if necessary, further developed because we want to be uncompromising in quality and competence.

HQ and GMP Grade DNA are required not only for vaccine production but also in the field of cancer research. Could you elaborate?

That's right, with our national and international customer base, we at PlasmidFactory are also well positioned in other research areas.

Exciting and no less important is the so-called CAR-T cell development. Ongoing research and advancements in CAR-T-cell technology currently unlock new possibilities for personalised and targeted cancer treatments. This groundbreaking approach has demonstrated remarkable success.

PlasmidFactory has developed and patented a method for producing CAR-T cells. In contrast to conventional methods, no viral vectors are used here, but PlasmidFactory's proprietary minicircle technology. Corresponding products are currently undergoing clinical trials.

Has the proprietary minicircle (MC) technology contributed to the success of CAR-T cell therapy?

Yes, without "MC" it does not work: Minicircle DNA contains practically only the "Gene of Interest" (GOI). Unnecessary sequences used only for the plasmid production process are completely removed. A safe and highly effective vector system is the result. It already meets the future regulatory requirements for gene therapy and vaccination.

We also produce customised minicircles using our unique, patented method: the plasmid containing GOI is the starting material. This is inserted into the so-called "parental plasmid". From this, the minicircle DNA molecule is produced by recombination, which consists almost exclusively of GOI.

The minicircle DNA, produced with our proprietary technology, is patented for use in CAR-T cells worldwide and is exclusively available at PlasmidFactory.

What kind of R&D activities do you have at PlasmidFactory?

The R&D activities of the PlasmidFactory are carried out in our laboratories, as well as in close cooperation with national and international partners.

For example, in the fields of:

- Optimisation of vectors to produce viral vectors (AAV or LV) or for efficient antibody or RNA production

- Development of resistance gene-free vector systems (e.g., minicircles)

- Investigation of the influence of various factors on the long-term stability of plasmid DNA (e.g., plasmid size, DNA concentration, storage medium, freezing and thawing conditions)

- DNA vaccines

- High cell density cultivation

- Single use technology in process technology

- Linear DNA vectors with loops at their ends (MIDGE)

- Vector development and gene transfer

Besides these scientific collaborations, we are also implementing strategic partnerships. In 2022, we partnered with ARCHIMED, a leading investment firm focused exclusively on healthcare industries. With ARCHIMED at our side, we are strengthened in expanding our business globally.

In addition, we have also found a more specific partner to support us in entering the Indian market.

Does this mean you have a new strategy to meet the increasing demand for highest quality DNA in the Indian market?

Yes, we do. After the success in handling COVID-19 in India, a large number of biotechnology and pharmaceutical firms are investing heavily in mRNA R&D. We are pleased to introduce Dr Nagaraj Rao, RRR Labs, Navi Mumbai, as our new partner in India. Dr Rao is well-known in the Indian pharma industry and among Indian biopharmaceutical and vaccine manufacturers for providing customers with state-of-the-art media and feeds for mammalian cell culture in recent years. Having lived in Germany for a decade earlier, his strong support and his role in bridging communication gaps between Indian and German companies play a crucial role in the success of such technology-driven businesses.

Being a biologist, how are you able to balance the business and research activities?

I am a biologist and researcher who manages the PlasmidFactory family. PlasmidFactory's products are manufactured by an energetic team of motivated colleagues.

Our work here is in the service of science, but of course, science also meets entrepreneurship in our company. We remain researchers for researchers!

With new convincing ideas and unique techniques, we want to advance biotechnology together - a simple part of my DNA.

Continued here:
We specialise in producing DNA of extraordinarily high purity for gene therapy and genetic vaccine research - BSI bureau

The Bioethics Observatory of the Catholic University of Valencia (UCV) invites an in-depth analysis of genetic research at the conference Genetic research: possibilities and risks. An approach from bioethics. This event, which will take place on July 4, 2024, at the UCV San Juan y San Vicente headquarters (18 Jorge Juan Street), will bring together experts from various fields to explore the ethical implications of scientific advances in this area.

In-person attendance at the congress requires prior registration, but the possibility of following it online will also be offered through the following link: https://youtube.com/live/.

The advancement of genetic research constitutes one of the spearheads of biomedical sciences and opens up enormous application possibilities in the fields of bioengineering, editing, and gene therapies. In parallel, with the development of these new tools, new bioethical dilemmas arise related to their fields of application, their safety and effectiveness, and regulation and control needs that urgently need to be addressed.

In our congress we propose a scientific approach to the current state of genetic research, analyzing the most recent evidence, such as that related to epigenetic processes, the therapeutic applications of the editing processes and obtaining mini human organs through bioengineering procedures, the aspects ethics of the heritability of potential changes and the need for ethical and legal regulation of related practices.

A prestigious team of expert researchers in each of these areas will provide us with updated access to this evidence that allows its bioethical assessment based on scientific rigor.

It is aimed at researchers, teachers, students and anyone with an interest in the field of Bioethics, and especially in genetics.

REGISTRATION HERE

PROGRAM

10:00. Institutional inauguration

10:15. Round Table: Epigenetics and genome editing: A scientific update

Ethics and epigenetics.

Luis Franco. Full member of the Royal Academy of Sciences of Spain and the Royal Academy of Medicine of the Valencian Community. University of Valencia.

10:45. Genome editing. Therapeutic advances and bioethical uncertainties.

Nicolas Jouve. Emeritus Professor of Genetics, former member of the Bioethics Committee of Spain.

11:15. Colloquium

Moderator:Luca Gmez Tatay. Professor of cell biology, biochemistry and bioethics. Catholic University of Valencia.

11:30. Coffee Break

12:00. Round Table: Bioengineering and gene therapy

Deciphering the potential of human mini-organs in the laboratory through ethics and bioengineering.

Nria Montserrat. ICREA research professor and principal researcher at the Institute of Bioengineering of Catalonia (IBEC).

12:30. Advances in the therapeutic application of gene editing systems based on CRISPR. Juan Roberto Rodrguez-Madoz. Researcher of the Hemato-Oncology Program. TOP. University of Navarra.

13:00. Colloquium.

Moderator:Jos Miguel Hernndez Andreu. Professor and researcher of biochemistry and molecular biology. Catholic University of Valencia.

16:15. Round Table: Ethical limits in genetic manipulation

Heritable gene editing in humans and future generations.

Vicente Bellver. Professor of Philosophy of Law at the University of Valencia. President of the Bioethics Committee of the Valencian Community.

16:45. Regulating gene editing: principles versus rules.

Federico de Montalvo. Vice Chancellor of Institutional Relations and Secretary General of the Universidad Pontificia Comillas.

17:15. Gene editing: what should really scare us?

igo De Miguel. Research Group of the Chair of Law and Human Genome of the Department of Public Law. University of the Basque Country Euskal Herriko Unibertsitatea.

17:45. Colloquium

Moderator:Mara Jos Salar. Coordinator of the Philosophy Degree. Professor at the Faculty of Economic and Social Legal Sciences of the Catholic University of Valencia.

18:00. Closure. Mr. Julio Tudela. Director of the Bioethics Observatory of the Catholic University of Valencia.

The rest is here:
Genetic research: possibilities and risks Exaudi - Exaudi

MALVERN, PA Ocugen, Inc. (NASDAQ: OCGN) announced a positive outcome from the Data and Safety Monitoring Board (DSMB) review of its Phase 1/2 ArMaDa clinical trial for OCU410, a gene therapy candidate aimed at treating geographic atrophy (GA), an advanced form of dry age-related macular degeneration (dAMD). GA affects approximately 2-3 million people in the U.S. and Europe.

To date, six patients with GA have participated in the trial. Three received a low dose of the therapy, while three others received a medium dose. The next phase will involve dosing an additional three patients with a high dose of OCU410.

The DSMB has recommended to proceed with dosing subsequent GA subjects with the high dose of OCU410 in the dose-expansion phase of the study and concurrently initiate Phase 2 dosing, said Dr. Peter Chang, Chair of the DSMB for the OCU410 clinical trial. No serious adverse events related to OCU410 have been reported to date in both low- and medium-dose cohorts. I believe that this marks a critical next step towards determining the maximum tolerated dose for OCU410 and is an important milestone for its clinical development.

Huma Qamar, Chief Medical Officer of Ocugen, expressed optimism about the therapys potential. We are delighted to report a second positive DSMB recommendation for the treatment of GA, which significantly builds on the favorable safety and tolerability profile exhibited by OCU410, she said. We are very enthusiastic about the potential of OCU410 as a potential one-time treatment for GA with a single sub-retinal injection.

The ArMaDa trial aims to assess the safety and efficacy of OCU410 administered subretinally. This trial is structured in two phases:

Phase 1: This is a multicenter, open-label, dose-ranging study. It includes three dose levels: low (2.510 vg/mL), medium (510 vg/mL), and high (1.510 vg/mL).

Phase 2: This phase will be a randomized, outcome assessor-blinded, dose-expansion study. Participants will be randomly assigned to one of two OCU410 treatment groups or an untreated control group in a 1:1:1 ratio.

The DSMBs positive review is significant for several reasons.

Safety and Tolerability: Initial results indicate that OCU410 is safe and well-tolerated at both low and medium doses. This builds confidence in the therapys potential for broader application.

Innovative Treatment Approach: Current treatments for GA target only the complement pathway and require multiple annual injections. OCU410 offers a different approach by addressing several pathways, including complement, lipid metabolism, inflammation, and oxidative stress. This could provide a more comprehensive and long-term benefit to patients.

Reduced Treatment Burden: If successful, OCU410 could reduce the number of required treatments to a single sub-retinal injection. This would significantly ease the treatment burden on patients compared to the frequent injections needed with existing therapies.

Gene therapy represents a frontier in medical research, offering hope for conditions that currently have limited treatment options. The success of OCU410 could pave the way for similar therapies targeting other complex diseases. As the population ages, the incidence of age-related conditions like GA is expected to rise, making innovative treatments even more crucial.

Ocugens progress with OCU410 thus far signals a promising development in the fight against dAMD. If the therapy continues to show positive results, it could transform the standard of care for millions of patients affected by this debilitating condition.

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Ocugen's Gene Therapy Shows Promise in Early Trial for Age-Related Macular Degeneration - MyChesCo

'Patient One' died on May 12 at a hospital in Sydney. (Representative pic)

A cryonics company has frozen its first client in Australia in the hope of bringing him back to life in the future. According to ABC News Australia, Southern Cryonics, which operates the Southern Hemisphere's first known cryonics facility, announced that it has cryogenically frozen its first client at its Holbrook facility. The client, a man in his 80s, died in Sydney before being frozen at minus 200 degrees Celsius. He has become what the company refers to as 'Patient One'.

"(It was) very stressful," Southern Cryonics' facility manager Philip Rhoades said, as per the outlet. "That was what was keeping me awake for a week because there are a number of different procedures to go through for different days, and there were a number of situations that might have gone wrong if we hadn't prepared properly," he added.

Mr Rhoades said even though his firm has been ready and preparing to accept bodies from this year, their first client was slightly unexpected. "There were a couple of other people who were existing members who we thought might be likely candidates for being the first but, as it turned out, it was someone who wasn't an existing member," Mr Rhoades said.

"His family rang up out of the blue and we had about a week to prepare and get organised," the manager stated. He explained that his team then tested all the cryonics equipment and were mostly prepared. "But it's still a little bit different when you are doing a real case," he said.

According to ABC News, 'Patient One' died on May 12 at a hospital in Sydney. The 10-hour process of preserving his body in the hope of bringing it back to life then began immediately. The man's body was moved into the hospital's cold room and packed in ice to bring it down to around 6 degrees Celsius. Doctors then pumped a liquid, which acts as a type of anti-freeze, through the body to help preserve cells and lower the body's temperature.

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The patient was then wrapped in a special type of sleeping bag and packed in dry ice. His body temperature was brought down to around minus 80 degrees Celsius, and he was transferred to Southern Cryonics' Holbrook facility the next day, where he remained on dry ice until a delivery of liquid nitrogen arrived. The man's temperature was then reduced further to minus 200 degrees Celsius before being deposited in a special tank that serves as a vacuum storage pod.

The whole process cost the client $170,000 with additional fees for medical teams to help with the preservation process, the outlet reported. This 10-hour process is designed to increase the likelihood of the person being resurrected, the company said.

Notably, the Holbrook facility currently holds one dewar that fits four bodies. The Holbrook site can fit up to 40 bodies with the possibility for expansion, which the company believes could soon be needed.

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Australian Cryonics Firm Freezes First Client In Hopes Of Bringing Him Back To Life In Future - NDTV