Genetherapy

Key mechanism controlling bone marrow stem cells could lead to new therapies – PharmaTimes – PharmaTimes

April 6th, 2024

Hoxa9 and b-catenin molecules are a rare population of self-renewing HSCs found in bone marrow

Researchers from Kings College Londons (KCL) Comprehensive Cancer Centre have identified a key mechanism that governs how bone marrow stem cells work, which could potentially lead to new therapeutic pathways.

The findings from the study will help researchers further understand the key principles involved in stem cell biology and could provide new avenues for the development of efficient stem cell therapeutics.

Researchers identified two molecules, Hoxa9 and b-catenin, that control when bone marrow stem cells rest and recover, as well as when they act and replicate.

Both molecules work together to control a rare population of self-renewing stem cells that are predominantly found in bone marrow, known as haematopoietic stem cells (HSCs).

HSCs are protected from environmental stressors and prevent exhaustion by resting, while inactive HSCs must become active again, replicating themselves by turning into different blood cells, including red blood cells, white blood cells and platelets, to replenish the blood system and respond to problems including infections, blood loss and other complications.

Researchers discovered that this active/inactive characteristic of HSCs plays a key role in bone marrow transplantation, a vital procedure for several diseases, including cancer, as it is critical for cancer stem cells, which sustain the disease and cause relapse.

Researchers suggest that understanding this process will be vital when designing better treatments.

In addition, the team identified a critical enzyme known as PRMT1, which mediates the functions of the two molecules, offering a potential new avenue for the development of efficient stem cell therapeutics.

Eric So, professor and chair in Leukaemia Biology, Comprehensive Cancer Centre, School of Cancer and Pharmaceutical Sciences, KCL and study lead, commented: Given the critical functions of stem cells in bone marrow transplant and cancer biology, [the] identification of a new druggable pathway not only will help to better understand the stem cell biology but also facilitates the development of more effective therapeutics in the future.

View post:
Key mechanism controlling bone marrow stem cells could lead to new therapies - PharmaTimes - PharmaTimes

Recommendation and review posted by Bethany Smith

Addition of ruxolitinib to standard graft-versus-host disease prophylaxis for allogeneic stem cell transplantation in … – Nature.com

April 6th, 2024

Georges GE, Doney K, Storb R. Severe aplastic anemia: allogeneic bone marrow transplantation as first-line treatment. Blood Adv. 2018;2:20208.

Article CAS PubMed PubMed Central Google Scholar

Zhao J, Ma L, Zheng M, Su L, Guo X. Meta-analysis of the results of haploidentical transplantation in the treatment of aplastic anemia. Ann Hematol. 2023;102:256587.

Article CAS PubMed Google Scholar

Esteves I, Bonfim C, Pasquini R, Funke V, Pereira NF, Rocha V, et al. Haploidentical BMT and post-transplant Cy for severe aplastic anemia: a multicenter retrospective study. Bone Marrow Transplant. 2015;50:6859.

Article CAS PubMed Google Scholar

Xu LP, Jin S, Wang SQ, Xia LH, Bai H, Gao SJ, et al. Upfront haploidentical transplant for acquired severe aplastic anemia: registry-based comparison with matched related transplant. J Hematol Oncol. 2017;10:25.

Article PubMed PubMed Central Google Scholar

Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366:799807.

Article CAS PubMed PubMed Central Google Scholar

Mart-Carvajal AJ, Anand V, Sol I. Janus kinase-1 and Janus kinase-2 inhibitors for treating myelofibrosis. Cochrane Database Syst Rev. 2015;2015:CD010298.

PubMed PubMed Central Google Scholar

Spoerl S, Mathew NR, Bscheider M, Schmitt-Graeff A, Chen S, Mueller T, et al. Activity of therapeutic JAK 1/2 blockade in graft-versus-host disease. Blood. 2014;123:383242.

Article CAS PubMed Google Scholar

Schroeder MA, Choi J, Staser K, DiPersio JF. The role of Janus kinase signaling in graft-versus-host disease and graft versus leukemia. Biol Blood Marrow Transplant. 2018;24:112534.

Article CAS PubMed Google Scholar

Hechinger AK, Smith BA, Flynn R, Hanke K, McDonald-Hyman C, Taylor PA, et al. Therapeutic activity of multiple common -chain cytokine inhibition in acute and chronic GVHD. Blood. 2015;125:57080.

Article CAS PubMed PubMed Central Google Scholar

Choi J, Ziga ED, Ritchey J, Collins L, Prior JL, Cooper ML, et al. IFNR signaling mediates alloreactive T-cell trafficking and GVHD. Blood. 2012;120:4093103.

Article CAS PubMed PubMed Central Google Scholar

Carniti C, Gimondi S, Vendramin A, Recordati C, Confalonieri D, Bermema A, et al. Pharmacologic inhibition of JAK1/JAK2 signaling reduces experimental murine acute GVHD while preserving GVT effects. Clin Cancer Res. 2015;21:37409.

Article CAS PubMed Google Scholar

Zeiser R, von Bubnoff N, Butler J, Mohty M, Niederwieser D, Or R, et al. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. N Engl J Med. 2020;382:180010.

Article PubMed Google Scholar

Zeiser R, Polverelli N, Ram R, Hashmi SK, Chakraverty R, Middeke JM, et al. Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease. N Engl J Med. 2021;385:22838.

Article CAS PubMed Google Scholar

Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, et al. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015;29:20628.

Article CAS PubMed PubMed Central Google Scholar

Krger N, Shahnaz Syed Abd Kadir S, Zabelina T, Badbaran A, Christopeit M, Ayuk F. et al. Peritransplantation ruxolitinib prevents acute graft-versus-host disease in patients with myelofibrosis undergoing allogenic stem cell transplantation. Biol Blood Marrow Transplant. 2018;24:21526.

Article PubMed Google Scholar

Gooptu M, Antin JH. GVHD prophylaxis 2020. Front Immunol. 2021;12:605726.

Article CAS PubMed PubMed Central Google Scholar

Borowitz MJ, Craig FE, Digiuseppe JA, Illingworth AJ, Rosse W, Sutherland DR, et al. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytom B Clin Cytom. 2010;78:21130.

Article Google Scholar

Donohue RE, Marcogliese AN, Sasa GS, Elghetany MT, Redkar AA, Bertuch AA, et al. Standardized high-sensitivity flow cytometry testing for paroxysmal nocturnal hemoglobinuria in children with acquired bone marrow failure disorders: a single center US study. Cytom B Clin Cytom. 2018;94:699704.

Article CAS Google Scholar

Zhang Y, Huo J, Liu L, Shen Y, Chen J, Zhang T, et al. Comparison of hematopoietic stem cell transplantation outcomes using matched sibling donors, haploidentical donors, and immunosuppressive therapy for patients with acquired aplastic anemia. Front Immunol. 2022;13:837335.

Article CAS PubMed PubMed Central Google Scholar

Han TT, Xu LP, Liu DH, Liu KY, Wang FR, Wang Y, et al. Recombinant human thrombopoietin promotes platelet engraftment after haploidentical hematopoietic stem cell transplantation: a prospective randomized controlled trial. Ann Hematol. 2015;94:11728.

Article CAS PubMed Google Scholar

Tang B, Huang L, Liu H, Cheng S, Song K, Zhang X, et al. Recombinant human thrombopoietin promotes platelet engraftment after umbilical cord blood transplantation. Blood Adv. 2020;4:382939.

Article CAS PubMed PubMed Central Google Scholar

Chinese Society of Hematology, Chinese Medical Association. [Chinese expert consensus on the management of hemorrhagic complications after hematopoietic stem cell transplantation(2021)]. Zhonghua Xue Ye Xue Za Zhi. 2021;42:27680.

Wang J, Zhou M, Xu JY, Zhou RF, Chen B, Wan Y. Comparison of antifungal prophylaxis drugs in patients with hematological disease or undergoing hematopoietic stem cell transplantation: a systematic review and network meta-analysis. JAMA Netw Open. 2020;3:e2017652.

Article PubMed PubMed Central Google Scholar

Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995;15:8258.

CAS PubMed Google Scholar

Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11:94556.

Article PubMed Google Scholar

Champlin RE, Horowitz MM, van Bekkum DW, Camitta BM, Elfenbein GE, Gale RP, et al. Graft failure following bone marrow transplantation for severe aplastic anemia: risk factors and treatment results. Blood. 1989;73:60613.

Article CAS PubMed Google Scholar

Lin F, Han T, Zhang Y, Cheng Y, Xu Z, Mo X, et al. The incidence, outcomes, and risk factors of secondary poor graft function in haploidentical hematopoietic stem cell transplantation for acquired aplastic anemia. Front Immunol. 2022;13:896034.

Article CAS PubMed PubMed Central Google Scholar

McLornan DP, Hernandez-Boluda JC, Czerw T, Cross N, Joachim Deeg H, Ditschkowski M, et al. Allogeneic haematopoietic cell transplantation for myelofibrosis: proposed definitions and management strategies for graft failure, poor graft function and relapse: best practice recommendations of the EBMT Chronic Malignancies Working Party. Leukemia. 2021;35:244559.

Article PubMed Google Scholar

Li J, Wang Y, Zhang Y, Zhang X, Pang A, Yang D, et al. Haematopoietic stem cell transplantation for hepatitis-associated aplastic anaemia and non-hepatitis-associated aplastic anaemia: a propensity score-matched analysis. Br J Haematol. 2023;201:117991.

Article PubMed Google Scholar

Aggarwal N, Manley AL, Chen J, Groarke EM, Feng X, Young NS. Effects of ruxolitinib on murine regulatory T cells are immune-context dependent. Exp Hematol. 2023;125126:169.

Article PubMed Google Scholar

Xu ZL, Huang XJ. Optimizing outcomes for haploidentical hematopoietic stem cell transplantation in severe aplastic anemia with intensive GVHD prophylaxis: a review of current findings. Expert Rev Hematol. 2021;14:44955.

Article CAS PubMed Google Scholar

Williams L, Cirrone F, Cole K, Abdul-Hay M, Luznik L, Al-Homsi AS. Post-transplantation cyclophosphamide: from HLA-haploidentical to matched-related and matched-unrelated donor blood and marrow transplantation. Front Immunol. 2020;11:636.

Article CAS PubMed PubMed Central Google Scholar

Bourgeois AL, Jullien M, Garnier A, Peterlin P, Bn MC, Guillaume T, et al. Post-transplant cyclophosphamide as sole GHVD prophylaxis after matched reduced-intensity conditioning allotransplant. Clin Transl Med. 2023;13:e1242.

Article CAS PubMed PubMed Central Google Scholar

Prata PH, Eikema DJ, Afansyev B, Bosman P, Smiers F, Diez-Martin JL, et al. Haploidentical transplantation and posttransplant cyclophosphamide for treating aplastic anemia patients: a report from the EBMT Severe Aplastic Anemia Working Party. Bone Marrow Transplant. 2020;55:10508.

Article CAS PubMed Google Scholar

Chang YJ, Zhao XY, Huang XJ. Granulocyte colony-stimulating factor-primed unmanipulated haploidentical blood and marrow transplantation. Front Immunol. 2019;10:2516.

Article CAS PubMed PubMed Central Google Scholar

Yao D, Tian Y, Li J, Li B, Lu J, Ling J, et al. Association between haploidentical hematopoietic stem cell transplantation combined with an umbilical cord blood unit and graft-versus-host disease in pediatric patients with acquired severe aplastic anemia. Ther Adv Hematol. 2022;13:20406207221134409.

Article CAS PubMed PubMed Central Google Scholar

Xu ZL, Huang XJ. Haploidentical transplants with a G-CSF/ATG-based protocol: experience from China. Blood Rev. 2023;62:101035.

Article CAS PubMed Google Scholar

Xu LP, Lu DP, Wu DP, Jiang EL, Liu DH, Huang H, et al. Hematopoietic stem cell transplantation activity in China 20202021 during the SARS-CoV-2 pandemic: a report from the Chinese Blood and Marrow Transplantation Registry Group. Transplant Cell Ther. 2023;29:136 e1e7.

Article PubMed Google Scholar

Yoshimi A, Baldomero H, Horowitz M, Szer J, Niederwieser D, Gratwohl A, et al. Global use of peripheral blood vs bone marrow as source of stem cells for allogeneic transplantation in patients with bone marrow failure. JAMA. 2016;315:198200.

Article PubMed Google Scholar

Kennedy GA, Varelias A, Vuckovic S, Le Texier L, Gartlan KH, Zhang P, et al. Addition of interleukin-6 inhibition with tocilizumab to standard graft-versus-host disease prophylaxis after allogeneic stem-cell transplantation: a phase 1/2 trial. Lancet Oncol. 2014;15:14519.

Article CAS PubMed Google Scholar

Chen YB, Shah NN, Renteria AS, Cutler C, Jansson J, Akbari M, et al. Vedolizumab for prevention of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Blood Adv. 2019;3:413646.

Article CAS PubMed PubMed Central Google Scholar

Lin Y, Gu Q, Lu S, Pan Z, Yang Z, Li Y, et al. Ruxolitinib improves hematopoietic regeneration by restoring mesenchymal stromal cell function in acute graft-versus-host disease. J Clin Investig. 2023;133:e162201.

Ryu DB, Lim JY, Kim TW, Shin S, Lee SE, Park G, et al. Preclinical evaluation of JAK1/2 inhibition by ruxolitinib in a murine model of chronic graft-versus-host disease. Exp Hematol. 2021;98:3646.e2.

Article CAS PubMed Google Scholar

Hlsdnker J, Ottmller KJ, Neeff HP, Koyama M, Gao Z, Thomas OS, et al. Neutrophils provide cellular communication between ileum and mesenteric lymph nodes at graft-versus-host disease onset. Blood. 2018;131:185869.

Article PubMed PubMed Central Google Scholar

Heine A, Held SA, Daecke SN, Wallner S, Yajnanarayana SP, Kurts C, et al. The JAK-inhibitor ruxolitinib impairs dendritic cell function in vitro and in vivo. Blood. 2013;122:1192202.

Article CAS PubMed Google Scholar

Sylvine P, Thomas S, Pirayeh E. Infections associated with ruxolitinib: study in the French Pharmacovigilance database. Ann Hematol. 2018;97:9134.

Article PubMed Google Scholar

Abedin S, McKenna E, Chhabra S, Pasquini M, Shah NN, Jerkins J, et al. Efficacy, toxicity, and infectious complications in ruxolitinib-treated patients with corticosteroid-refractory graft-versus-host disease after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2019;25:168994.

Article CAS PubMed Google Scholar

Hong X, Chen Y, Lu J, Lu Q. Addition of ruxolitinib in graft-versus-host disease prophylaxis for pediatric -Thalassemia major patients after allogeneic stem cell transplantation: a retrospective cohort study. Pediatr Transplant. 2023;27:e14466.

Article CAS PubMed Google Scholar

Zhang B, Chen L, Zhou J, Zu Y, Gui R, Li Z, et al. Ruxolitinib early administration reduces acute GVHD after alternative donor hematopoietic stem cell transplantation in acute leukemia. Sci Rep. 2021;11:8501.

Article CAS PubMed PubMed Central Google Scholar

Zhao Y, Shi J, Luo Y, Gao F, Tan Y, Lai X, et al. Calcineurin inhibitors replacement by ruxolitinib as graft-versus-host disease prophylaxis for patients after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2020;26:e128e33.

Article CAS PubMed Google Scholar

Morozova EV, Barabanshikova MV, Moiseev IS, Shakirova AI, Barhatov IM, Ushal IE, et al. A prospective pilot study of graft-versus-host disease prophylaxis with post-transplantation cyclophosphamide and ruxolitinib in patients with myelofibrosis. Acta Haematol. 2021;144:15865.

Article CAS PubMed Google Scholar

See the rest here:
Addition of ruxolitinib to standard graft-versus-host disease prophylaxis for allogeneic stem cell transplantation in ... - Nature.com

Recommendation and review posted by Bethany Smith

Alzheimer’s Could Be Transmitted via Bone Marrow Transplants, Researchers Say – PEOPLE

April 6th, 2024

A new study found that Alzheimers could potentially be accelerated by bone marrow transplants from donors with the disease.

On Thursday, a group of researchers from the University of British Columbia in Canada published a study in the scientific journal Stem Cell Reports that found that lab mice that received bone marrow transplants from other mice that had a protein associated with Alzheimer's experienced rapid cognitive decline.

The study, researchers said, could help scientists start to pinpoint what exactly contributes to Alzheimer's and other types of cognitive decline especially because so much is unknown about Alzheimer's, including whether it's caused by the brain or by genetic or environmental factors.

"This supports the idea that Alzheimers is a systemic disease where amyloids that are expressed outside of the brain contribute to central nervous system pathology," Wilfred Jefferies, an immunologist and an author on the study, told Neuroscience News.

As we continue to explore this mechanism, Alzheimers disease may be the tip of the iceberg and we need to have far better controls and screening of the donors used in blood, organ and tissue transplants as well as in the transfers of human-derived stem cells or blood products," Jefferies added.

In the study, the researchers used both healthy mice and mice showing signs of Alzheimer's disease, and transplanted bone marrow to them from mice with a hereditary form of Alzheimer's. The healthy mice began developing signs of Alzheimer's at 9 months old, and the mice that already had the Alzheimer's protein began to experience cognitive decline at 6 months old.

"The fact that we could see significant behavioral differences and cognitive decline in the APP-knockouts at 6 months was surprising but also intriguing because it just showed the appearance of the disease that was being accelerated after being transferred," the study's first author, Chaahat Singh, told Neuroscience News.

Never miss a story sign up for PEOPLE's free daily newsletter to stay up-to-date on the best of what PEOPLE has to offer, from celebrity news to compelling human interest stories.

The University of British Columbia researchers wrote that bone marrow and other medical donors should be screened for Alzheimer's before they are able to give a transfusion.

However, several other scientists who spoke with Medscape warned that the risk of a human receiving Alzheimer's via a bone marrow or stem cell transfer is very low.

Paul Morgan, a dementia researcher at Cardiff University in the United Kingdom, told the scientific outlet that the study involved a "very specific experimental situation," and that it is a "gargantuan leap" to say that there is a significant risk in humans for spreading Alzheimer's through transplants.

Go here to see the original:
Alzheimer's Could Be Transmitted via Bone Marrow Transplants, Researchers Say - PEOPLE

Recommendation and review posted by Bethany Smith

Behind the science – DVM 360

April 6th, 2024

Dog DNA tests are on the risebut are they reliable? – National Geographic

April 6th, 2024

Breed is a surprisingly complicated question, says Halie Rando, an assistant professor of computer science at Smith College who led the research. A dogs genetics may point to one breed, she says. But widely accepted breed definitions were defined in a time before DNA analysis, and Rando says that genetic testing can sometimes clash with pet owners preconceived notions about their dogs.

Even experienced humans, it turns out, are terrible at identifying breed by sight: In a recent study of 459 shelter dogs at two humane societies in Arizona and California, DNA analysis pinpointed found 125 distinct breeds, including five percent that were purebred. Nonetheless, neither the scientists nor the experienced shelter workers were able to reliably identify mixed-breed dogs, which made up nearly 90 percent of the canine cohort.

Mixed breeds can prove tricky even with DNA dataand since genetic testing relies on information about the genes of dogs with identifiable breeds, a DNA test is only as good as its genetic dataset.

As a consumer, you might value a company that is more transparent and has a diverse [DNA] panel, says Greene. He encourages consumers to do their research before submitting a sampleand double-check that the panel used by the testing company includes the breeds you suspect might be in the mix.

Even if you do get accurate information about your dogs breed, it might not be as linked to its behavior as you might think. A 2022 genetic analysis of more than 2,000 purebred and mixed-breed dogs found behavior was linked more closely to individual dogs than breeds, concluding that dog breed is generally a poor predictor of individual behavior.

Excerpt from:
Dog DNA tests are on the risebut are they reliable? - National Geographic

Recommendation and review posted by Bethany Smith

INTERACT COALITION FORMED TO ADVANCE PATIENT ACCESS TO GENETIC TESTING FOR HEREDITARY … – PR Newswire

April 6th, 2024

SAN DIEGO, April 3, 2024 /PRNewswire/ -- Leading commercial organizations and patient advocacy groups in the field of cancer genetics today announced the founding of the Inter-Organization Cancer Genetics Clinical Evidence Coalition (INTERACT), a coalition whose mission is to increase evidence-based access to genetic testing for people with or at risk of hereditary cancers.

Founding laboratory members include organizer Ambry Genetics, a subsidiary of REALM IDx, Illumina, Myriad Genetics, and Quest Diagnostics. Volpara Health has also recently joined the coalition. Founding patient advocacy organization members include AliveAndKickn and FORCE. The coalition seeks to provide a collective voice in support of the progression of medical professional and industry guidelines for genetic testing for inherited mutations that increase cancer risk.

With growing insight into the role of genetic testing in cancer risk management and treatment, the population of individuals who benefit from knowing their genetic mutation status continues to increase. As leaders in the genetic testing and hereditary cancer field, the founding members believe it is their responsibility to help drive awareness and inform changes that will equalize access for those whose outcomes could benefit most from testing.

One of the primary objectives of INTERACT is to ensure policy and guidelines keep pace with the growing body of evidence surrounding inherited cancer risk.

Hereditary cancer genetic testing has been shown to improve outcomes by identifying those most at risk and informing management strategies. For instance, patients who test positive for a BRCA1 or BRCA2 mutation have up to 87% lifetime risk for breast cancer, and up to 40% lifetime risk for ovarian cancer.1,2 In addition, there are numerous other genes that increase risk for various forms of cancer. Armed with this information, patients and physicians can improve management through increased surveillance, chemoprevention, targeted therapeutics or risk-reducing surgical measures. As an example, studies have shown that prophylactic mastectomy in BRCA1/2 mutation carriers results in up to a 97% reduction in the risk for contralateral breast cancer, while salpingo-oophorectomy reduced ovarian cancer incidence by 69-100%.1,2

Despite the benefits of a patient and their provider knowing mutation status, disparities in access and uptake of cancer genetics services are well documented.3 INTERACT intends to improve access to genetic testing, with the goal of reaching vulnerable populations who may not currently be aware of their risk or their need for increased screening or other interventions.

"With Lynch syndrome, one of the most common hereditary cancer syndromes, patients have up to 80% lifetime risk for colorectal cancer4, but an estimated 95% of at-risk individuals have not been identified5," said Robin Dubin, Executive Director of AliveAndKickn. "To really improve survival rates with informed screening strategies, we need to help drive education and policies that support genetic testing for all those at risk."

Among the challenges to broadening access to genetic testing for hereditary cancer risk is a time lag in updating guidelines and medical policies after the publication of new medical literature. INTERACT will work to bring these differences to the attention of guideline committees and medical professional societies in an effort to bridge the gaps and reduce disparities in access to appropriate testing nationwide.

About INTERACT The mission of INTERACT is to bring together specialized genetic testing laboratories and patient advocacy groups to support the progression and evolution of medical policy and industry guidelines for cancer genetic testing. Our members are recognized institutions in the field of cancer genetics. Current commercial members include Ambry Genetics, a subsidiary of REALM IDx, Illumina, Myriad Genetics, Quest Diagnostics, and Volpara Health. Advocacy members include AliveAndKickn and FORCE: Facing Our Risk of Cancer Empowered. We seek to develop the evidence base and rationale to inform changes in cancer-related genetic testing policies to expand patient access to evidence-based testing.

For more information, visit: https://interactcoalition.org/

References:

Contact: [emailprotected]

SOURCE INTERACT Coalition

Read more:
INTERACT COALITION FORMED TO ADVANCE PATIENT ACCESS TO GENETIC TESTING FOR HEREDITARY ... - PR Newswire

Recommendation and review posted by Bethany Smith

80% of rare diseases are genetic. That’s why whole genome sequencing can help with diagnoses – GPB News

April 6th, 2024

Jansen Jones wasnt using her hands or legs.

She lacked muscle tone and was too weak to bear weight using her extremities.

The baby could lift and move her head, but she didnt seem as strong as a 5-month-old should be, her mother believed.

"She is my third child," Suzanne Jones said, which means she's witnessed developmental milestones twice previously.

Doctors at Childrens Healthcare of Atlanta diagnosed Jansen with a nonspecific, global developmental delay.

We were just told, She's behind. No big deal. Do some physical therapy, Jones said.

But a lot of babies seem really strong, and it was clear to Jones that Jansen was not.She would curl up in a sort of ball, and sat looking sweet and happy, but did not engage with her environment.

A neurologist said a muscle biopsy might explain the deficiency, but there are false positives with muscle biopsies.

"That is invasive and leaves a scar and scared us," Jones said. "You know, you're basically cutting on her arm or leg."

When Jansen didn't babble as expected, they started speech therapy. Then, they added occupational therapy.

"We just did hours and hours of therapies nonstop for years," Jones said.

A neuro-psychological exam led doctors to say Jansen was intellectually disabled.

This happened about the same time as rare, fleeting seizures caused Jansen to space out for a second or two.

An electroencephalogram (EEG) test confirmed abnormal electrical activity in her brain.

"Well, they just said she has epilepsy," Jones said.

But Jones said the family continually witnessed symptoms that suggested that Jansen was struggling in different ways.

The idea of genetic testing came up by the time Jansen was 3 years old.

"In my opinion, if it's genetics, that's the underlying cause of everything and so that should show us what is going on," Jones said.

Jones doctors described the 46 chromosomes in the body as chapters in a book. Whole exome sequencing was like scanning the book to see whether any chapters were missing or duplicated.

For example,the characteristic features and developmental problems of a person with Down Syndrome is caused by an extra chromosome 21.

Think of that as Chapter 21.

But after having Jansen's whole exome sequenced, they still had no solid answers.

"And so we got results back when she was 3 and it did not show us what was going on," Jones said.

All the Joneses could do was treat Jansen's symptoms, which included behavior problems.

Despite managing Jansen through applied behavior therapy and medication, Jansen acted out and shecouldn't control it. Nightmares made her want to sleep in bed with her parents.

"It's not clear to me why the whole exome sequencing didn't catch it," Jones said. But it's not an infallible test.

An exome is a collection of 180,000 exons responsible for protein coding, but the human exome only comprises about 1% of the human genome.

Now, whole genome sequencing is available.

"And that is what ended up catching it," Jones said.

Jansen was diagnosed just before her 11th birthday with a disorder caused by a single gene mutation: SYNGAP1.

"This mutation was discovered only a year before Jansen was born."

Jansen's frustration stemmed from an inability to reason and communicate.

She turned 13 in October 2023.

"It's not easy," Jones said. "They have a SYNGAP snap. Sometimes their brain just [goes] haywire. And you can't you can't reason with somebody who can't reason. So behaviors can be really difficult."

"Compared to other single-gene mutations that cause epilepsy, SYNGAP1 children have a lot of problems with behavior," Jones said. "And luckily with that being a spectrum, my child has those issues, but it's not constant; it's not as prevalent."

If you have a rare disease, there is an 80% chance that its genetic. That doesnt mean the cause has been identified yet.

Karen Grinzaid with Emory University School of Medicine said she believes everyone planning a family should conduct genetic testing.

"The reason is there are genetic diseases that can happen that haven't shown up in your family yet," she said.

We all carry a number of recessive genes, but we don't know what those genes are unless either we have an affected child, or we do genetic testing.

But a whole genome test like Jansens might make would-be parents more nervous than is necessary.

"When you do broader testing like that, it may turn up problems where it's not clear what the implications are," Grinzaid said. "So, I just can't overemphasize the importance of genetic counseling to help people through this journey."

Suzanne Jones said even though her daughters diagnosis hasnt changed her daughters developmental issues, the genomic sequencing was worth it.

"It's an answer," she said. "We can finally say we understand what all these different symptoms are caused by."

And that, Jones said, makes it a lot less scary to be a parent.

See the original post:
80% of rare diseases are genetic. That's why whole genome sequencing can help with diagnoses - GPB News

Recommendation and review posted by Bethany Smith

Personalized care and treatment plans – DVM 360

April 6th, 2024

Quest Diagnostics and Broad Clinical Labs to Evaluate Whole Genome Sequencing as First-Line Genetic Test for … – PR Newswire

April 6th, 2024

Aim to demonstrate whole genome sequencing can replace the standard diagnostic cascade, for potentially faster diagnosis and lower costs

SECAUCUS, N.J., April 2, 2024 /PRNewswire/ --Quest Diagnostics (NYSE: DGX), a leader in diagnostic information services, and Broad Clinical Labs, the world expert in whole genome sequencing (WGS), today announced a research collaboration designed to demonstrate the clinical value of WGS as a first-line genetic test for postnatal diagnosis of developmental delay disorders.

The parties expect to demonstrate that WGS can provide insightsfrom a single blood testthat are at least as clinically accurate as the multiple conventional tests providers typically use to diagnose a patient.

"We are delighted to bring the experience and expertise of Broad Clinical Labs to this innovative collaboration with Quest. We believe that the genome is a platform upon which many research, screening, and diagnostic tests can be built resulting in benefits for patients and providers alike," said Niall J. Lennon, Ph.D., Chief Scientific Officer of Broad Clinical Labs and Senior Director of Genomics at the Broad Institute of MIT and Harvard.

"WGS has the power to enable a new diagnostic paradigm, where a physician can access genetic insights faster on the patient's diagnostic journey--without multiple doctor visits and lab tests," said Mark Gardner, Senior Vice President, Molecular Genomics and Oncology at Quest Diagnostics. "Broad is the leader in genomic science and Quest is the leader in laboratory testing at scale, so together we have the right combination of skills to explore the potential of WGS to replace the conventional model."

"This research initiative by Broad and Quest involves both phenotypic and genotypic data sharing in an effort to further enhance interpretation of genomic tests and the understanding of development delay," said Heidi Rehm, Ph.D., FACMG, Medical Director of Broad Clinical Labs, and Chief Genomics Officer of Massachusetts General Hospital. "This type of collaboration between commercial laboratories and research institutions is vital to advance the field of genetic testing and increase utility and economic value."

Creating a New Testing Model to Simplify and Speed Diagnosis

Nearly 2% of children manifest intellectual disability. Yet, it can take weeks, months, or even years to identify the underlying cause of intellectual disability or developmental delay, causing a "diagnostic odyssey" for patients and their families. Identification of an underlying diagnosis can lead to changes in management that "will influence mortality, morbidity, and reduce the burden on patients and families searching for answers," according to the American College of Medical Genetics and Genomics.

While the ACMG recommends WGS for first-line genetic testing for intellectual disability and developmental delay, some providers continue to follow prior guidelines that recommend chromosomal microarray (CMA) as a first-line test. CMA is less informative than WGS, and patients whose findings are negative by CMA can require additional rounds of testing, such as with narrow gene tests or genetic panels or exome sequencing, until a cause is found.

"Now that the $100 genome is moving closer to reality, it's time to reconsider the way genetic testing is utilized and reimbursed and, ultimately, end the diagnostic odyssey for children and their families," Mr. Gardner added.

Through the collaboration, Quest will provide de-identified data, including phenotypic (a person's observable traits), and blood, saliva, and buccal swab specimens it has tested for developmental delays using CMA and other tests. Broad will then perform WGS on the de-identified specimens to determine concordance between the methods.

The collaboration will also explore the potential of WGS to provide answers for Fragile X syndrome. Unlike CMA or exome sequencing, WGS can rule out Fragile X as a cause of developmental delay and signal the need for additional confirmatory testing in those whose results suggest it as a possible cause of developmental delay.

Broad Clinical Laboratories, previously known as Clinical research sequencing platform, was founded in 2013 as a non-profit subsidiary of Broad Institute of MIT and Harvard to accelerate the genomics community and the world toward a better understanding, diagnosis, and treatment of disease by pursuing projects, developing products, and driving adoption of cutting edge -omics technologies and novel molecular assays.

Broad Clinical Labs is a leader in human whole genome sequencing, having sequenced over 600,000 genomes in service of its mission to accelerate the understanding and diagnosis of human disease. http://www.broadclinicallabs.org

About Quest DiagnosticsQuest Diagnostics works across the healthcare ecosystem to create a healthier world, one life at a time. We provide diagnostic insights from the results of our laboratory testing to empower people, physicians and organizations to take action to improve health outcomes. Derived from one of the world's largest databases of deidentified clinical lab results, Quest's diagnostic insights reveal new avenues to identify and treat disease, inspire healthy behaviors and improve healthcare management. Quest Diagnostics annually serves one in three adult Americans and half the physicians and hospitals in the United States, and our nearly 50,000 employees understand that, in the right hands and with the right context, our diagnostic insights can inspire actions that transform lives and create a healthier world. http://www.QuestDiagnostics.com.

SOURCE Quest Diagnostics

Here is the original post:
Quest Diagnostics and Broad Clinical Labs to Evaluate Whole Genome Sequencing as First-Line Genetic Test for ... - PR Newswire

Recommendation and review posted by Bethany Smith

NICE backs post-stroke genetic testing to identify most suitable treatment options – PMLiVE

April 6th, 2024

Patients in England and Wales who have recently had an ischaemic stroke or transient ischaemic attack could be offered genetic testing to help inform their treatment, following backing from the National Institute for Health and Care Excellence (NICE).

The agency has launched a second consultation on recommendations that clinicians should offer CYP2C19 genotype testing when considering treatment with clopidogrel, an anti-platelet therapy currently recommended as a treatment option for patients at risk of a secondary stroke.

Approximately 35,850 people in England, Wales and Northern Ireland have a non-minor stroke every year.

An estimated 32% of people in the UK have at least one of the highlighted CYP2C19 gene variants, and evidence has suggested that those with these variants have an increased risk of another stroke when taking clopidogrel.

If the genotype test discovers that patients have one of the CYP2C19 gene variants, alternative stroke-prevention treatments would be offered.

Professor Jonathan Benger, chief medical officer at NICE, said: Recommending a genetic test that can offer personalised care to thousands of people who have a stroke each year will be a step forward in ensuring people receive the best possible treatment.

People who are currently taking clopidogrel will not receive retrospective testing and should continue with the treatment until they and their NHS clinician consider it appropriate to stop, NICE outlined.

It added that laboratory-based CYP2C19 genotype testing is its preferred option, followed by the Genedrive CYP2C19 ID Kit point-of-care test and, if neither of the first two options are available, the Genomadix Cube point-of-care test would be used.

The agencys committee has suggested that a phased rollout could be implemented when introducing laboratory-based testing, with testing set to initially be offered to people with a higher risk of stroke recurrence.

Juliet Bouverie, from the Stroke Association, said: Stroke devastates lives and leaves people with life-long disability.

We know that many stroke survivors spend the rest of their lives fearing another stroke, so its great to see that more people could be given appropriate help to significantly cut their risk of recurrent stroke.

View post:
NICE backs post-stroke genetic testing to identify most suitable treatment options - PMLiVE

Recommendation and review posted by Bethany Smith

NICE launches second consultation on genetic testing to guide treatment after a stroke – NICE

April 6th, 2024

A second consultation on recommendations that clinicians should offer CYP2C19 genotype testing when considering treatment with clopidogrel after an ischaemic stroke or Transient Ischaemic Attack (a mini stroke) has begun today, Wednesday 3 April 2024.

NICE currently recommends clopidogrel as a treatment option for people at risk of a secondary stroke. For some people with certain variations in a gene called CYP2C19 other treatments could work better. The genotype test would identify people who have the gene variants so they can be offered an alternative treatment.

The draft guidance recommends testing only for people who have very recently had a stroke or TIA. This is because the risk of another event is higher at this time and therefore so is the potential benefit of testing. As the risk of a recurrent stroke or a mini stroke reduces over time, so does the benefit of testing.

For this reason, those people already taking clopidogrel will not be offered retrospective testing.

People who are currently taking clopidogrel should continue with the treatment until they and their NHS clinician consider it appropriate to stop.

Laboratory-based CYP2C19 genotype testing was the committees preferred option followed by the Genedrive CYP2C19 ID Kit point-of-care test. If neither of the first two options are available, the Genomadix Cube point-of-care test can be used.

The NICE committee suggested that a phased rollout could be used when introducing laboratory-based testing with testing initially offered to people with a higher risk of stroke recurrence who would benefit most from it, such as people who have had a non-minor stroke. The committee recognised that it will take time to build up the testing capacity as no testing is currently undertaken to find out if clopidogrel is a suitable treatment.

Around 35,850 people in England, Wales and Northern Ireland have a non-minor stroke each year.

An estimated 32% of people in the UK have at least one of the highlighted CYP2C19 gene variants. They are more common in people with an Asian family background but can be found in people of any ethnicity. Evidence has suggested that people with these variants have an increased risk of another stroke when taking clopidogrel compared to those without them.

If the test discovers they have one of the CYP2C19 gene variants, the person can be treated with another medicine to prevent future strokes.

Around 11 million items of clopidogrel are dispensed each year at a cost of around 16 million to the NHS.

Professor Jonathan Benger, chief medical officer at NICE, said:Recommending a genetic test that can offer personalised care to thousands of people who have a stroke each year will be a step forward in ensuring people receive the best possible treatment.

We recognise that capacity within laboratories will need to increase before everyone who has had a new stroke or mini-stroke can receive testing. While point of care testing is an alternative, our committee has identified that initially those people who could benefit most from laboratory-based testing are those who have had a non-minor stroke.

Anyone who is currently being treated with clopidogrel should continue with the treatment. They should only stop after discussing the options with their clinician.

Juliet Bouverie, from the Stroke Association, said:"Stroke devastates lives and leaves people with life-long disability. We know that many stroke survivors spend the rest of their lives fearing another stroke, so it's great to see that more people could be given appropriate help to significantly cut their risk of recurrent stroke.

"Getting on the right medication and taking it as advised can really go far to prevent further strokes. If you have been prescribed clopidogrel, you need to keep taking it. If you're worried about your risk of another stroke, you should speak to your doctor."

Read the original:
NICE launches second consultation on genetic testing to guide treatment after a stroke - NICE

Recommendation and review posted by Bethany Smith

Seven diseases that CRISPR technology could cure – Labiotech.eu

April 6th, 2024

CRISPR technology offers the promise to cure human genetic diseases with gene editing. This promise became a reality when the worlds first CRISPR therapy was approved by regulators to treat patients with sickle cell disease and beta-thalassemia last year.

American biopharma Vertex Pharmaceuticals CASGEVY works by turning on the BCL11A gene, which codes for fetal hemoglobin. While this form of hemoglobin is produced before a baby is born, the body begins to deactivate the gene after birth. As both sickle cell disease and beta-thalassemia are blood disorders that affect hemoglobin, by switching on the gene responsible for fetal hemoglobin production, CASGEVY presents a curative, one-time treatment for patients.

As CASGEVYs clearance is a significant milestone, the technology has come a long way. CRISPR/Cas9 was first used as a gene-editing tool in 2012. Over the years, the technology exploded in popularity thanks to its potential for making gene editing faster, cheaper, and easier than ever before.

CRISPR is short for clustered regularly interspaced short palindromic repeats. The term makes reference to a series of repetitive patterns found in the DNA of bacteria that form the basis of a primitive immune system, defending them from viral invaders by cutting their DNA.

Using this natural process as a basis, scientists developed a gene-editing tool called CRISPR/Cas that can cut a specific DNA sequence by simply providing it with an RNA template of the target sequence. This allows scientists to add, delete, or replace elements within the target DNA sequence. Slicing a specific part of a genes DNA sequence with the help of the Cas9 enzyme, aids in DNA repair.

This system represented a big leap from previous gene-editing technologies, which required designing and making a custom DNA-cutting enzyme for each target sequence rather than simply providing an RNA guide, which is much simpler to synthesize.

CRISPR gene editing has already changed the way scientists do research, allowing a wide range of applications across multiple fields. Here are some of the diseases that scientists aim to tackle using CRISPR/Cas technology, testing its possibilities and limits as a medical tool.

Cancer is a complex, multifactorial disease, and a cure remains elusive. There are hundreds of different types of cancer, each with a unique mutation signature. CRISPR technology is a game-changer for cancer research and treatment as it can be used for many things, including screening for cancer drivers, identifying genes and proteins that can be targeted by cancer drugs, cancer diagnostics, and as a treatment.

China spearheaded the first in-human clinical trials using CRISPR/Cas9 as a cancer treatment. The study tested the use of CRISPR to modify immune T cells extracted from a patient with late-stage lung cancer. The gene-editing technology was used to remove the gene that encodes for a protein called PD-1 that some tumor cells can bind to to block the immune response against cancer. This protein found on the surface of immune cells is the target of some cancer drugs termed checkpoint inhibitors.

CRISPR technology has also been applied to improve the efficacy and safety profiles of cancer immunotherapy, such as CAR-T cell and natural killer cell therapies. In the U.S., CRISPR Therapeutics is one of the leading companies in this space, developing off-the-shelf, gene-edited T cell therapies using CRISPR, with two candidates targeting CD19 and CD70 proteins in clinical trials.

In 2022, the FDA granted Orphan Drug designation to Intellia Therapeutics CRISPR/Cas9-gene-edited T cell therapy for acute myeloid leukemia (AML). Currently, Vor BioPharmas VOR33 is undergoing phase 2 trials to treat AML, and the CRISPR trial is one to watch, according to a report published by Clinical Trials Arena earlier this year.

However, CRISPR technology still has limitations, including variable efficiency in the genome-editing process and off-target effects. Some experts have recommended that the long-term safety of the approach remain under review. Others have suggested using more precise gene-editing approaches such as base editing, an offshoot of CRISPR that hit the clinic in the U.S. last year.

There are several ways CRISPR could help us in the fight against AIDS. One is using CRISPR to cut the viral DNA that the HIV virus inserts within the DNA of immune cells. This approach could be used to attack the virus in its hidden, inactive form, which is what makes it impossible for most therapies to completely get rid of the virus.

The first ever patient with HIV was dosed with a CRISPR-based gene-editing therapy in a phase 1/2 trial led by Excision Biotherapeutics and researchers at the Lewis Katz School of Medicine at Temple University in Philadelphia back in 2022.

The decision to move the therapy to the clinic was bolstered by the success of an analog of the drug EBT-101 called EBT-001 in rhesus macaques infected with simian immunodeficiency virus (SIV). In a phase 1/2 study, EBT-101 was found to be safe.

Another approach could make us resistant to HIV infections. A small percentage of the worlds population is born with a natural resistance to HIV, thanks to a mutation in a gene known as CCR5, which encodes for a protein on the surface of immune cells that HIV uses as an entry point to infect the cells. The mutation changes the structure of the protein so that the virus is no longer able to bind to it.

This approach was used in a highly controversial case in China in 2018, where human embryos were genetically edited to make them resistant to HIV infections. The experiment caused outrage among the scientific community, with some studies pointing out that the CRISPR babies might be at a higher risk of dying younger.

The general consensus seems to be that more research is needed before this approach can be used in humans, especially as recent studies have pointed out this practice can have a high risk of unintended genetic edits in embryos.

Cystic fibrosis is a genetic disease that causes severe respiratory problems. Cystic fibrosis can be caused by multiple different mutations in the target gene CFTR more than 700 of which have been identified making it difficult to develop a drug for each mutation. With CRISPR technology, mutations that cause cystic fibrosis can be individually edited.

In 2020, researchers in the Netherlands used base editing to repair CFTR mutations in vitro in the cells of people with cystic fibrosis without creating damage elsewhere in their genetic code. Moreover, aiming to strike again with yet another win is the duo Vertex Pharmaceuticals and CRISPR Therapeutics, which have collaborated to develop a CRISPR-based medicine for cystic fibrosis. However, it might be a while until it enters the clinic as it is currently in the research phase.

Duchenne muscular dystrophy is caused by mutations in the DMD gene, which encodes for a protein necessary for the contraction of muscles. Children born with this disease experience progressive muscle degeneration, and existing treatments are limited to a fraction of patients with the condition.

Research in mice has shown CRISPR technology could be used to fix the multiple genetic mutations behind the disease. In 2018, a group of researchers in the U.S. used CRISPR to cut at 12 strategic mutation hotspots covering the majority of the estimated 3,000 different mutations that cause this muscular disease. Following this study, Exonics Therapeutics was spun out to further develop this approach, which was then acquired by Vertex Pharmaceuticals for approximately $1 billion to accelerate drug development for the disorder. Currently, Vertex is in the research stage, and is on a mission to restore dystrophin protein expression by targeting mutations in the dystrophin gene.

However, a CRISPR trial run by the Boston non-profit Cure Rare Disease targeting a rare DMD mutation resulted in the death of a patient owing to toxicity back in November 2022. Further research is needed to ensure the safety of the drug to treat the disease.

Huntingtons disease is a neurodegenerative condition with a strong genetic component. The disease is caused by an abnormal repetition of a certain DNA sequence within the huntingtin gene. The higher the number of copies, the earlier the disease will manifest itself.

Treating Huntingtons can be tricky, as any off-target effects of CRISPR in the brain could have very dangerous consequences. To reduce the risk, scientists are looking at ways to tweak the genome-editing tool to make it safer.

In 2018, researchers at the Childrens Hospital of Philadelphia revealed a version of CRISPR/Cas9 that includes a self-destruct button. A group of Polish researchers opted instead for pairing CRISPR/Cas9 with an enzyme called nickase to make the gene editing more precise.

More recently, researchers at the University of Illinois Urbana-Champaign used CRISPR/Cas13, instead of Cas9, to target and cut mRNA that codes for the mutant proteins responsible for Huntingtons disease. This technique silences mutant genes while avoiding changes to the cells DNA, thereby minimizing permanent off-target mutations because RNA molecules are transient and degrade after a few hours.

In addition, a 2023 study published in Nature went on to prove that treatment of Huntingtons disease in mice delayed disease progression and that it protected certain neurons from cell death in the mice.

With CASGEVYs go-ahead to treat transfusion-dependent beta-thalassemia and sickle cell disease in patients aged 12 and older, this hints that CRISPR-based medicines could even be a curative therapy to treat other blood disorders like hemophilia.

Hemophilia is caused by mutations that impair the activity of proteins that are required for blood clotting. Although Intellia severed its partnership with multinational biopharma Regeneron to advance its CRISPR candidate for hemophilia B a drug that was recently cleared by the FDA to enter the clinic the latter will take the drug ahead on its own.

As hemophilia B is caused by mutations in the F9 gene, which encodes a clotting protein called factor IX (FIX), Regenerons drug candidate uses CRISPR/Cas9 gene editing to place a copy of the F9 gene in cells in order to get the taps running for FIX production.

The two biopharmas will continue their collaboration in developing their CRISPR candidate to treat hemophilia A, which manifests as excessive bleeding because of a deficit of factor VIII. The therapy is currently in the research phase.

While healthcare companies were creating polymerase chain reaction (PCR) tests to screen for COVID-19 in the wake of the pandemic, CRISPR was also being put to use for speedy screening. A study conducted by researchers in China in 2023, found that the CRISPR-SARS-CoV-2 test had a comparable performance with RT-PCR, but it did have several advantages like short assay time, low cost, and no requirement for expensive equipment, over RT-PCRs.

To add to that, the gene editing tool could fight COVID-19 and other viral infections.

For instance, scientists at Stanford University developed a method to program a version of the gene editing technology known as CRISPR/Cas13a to cut and destroy the genetic material of the virus behind COVID-19 to stop it from infecting lung cells. This approach, termed PAC-MAN, helped reduce the amount of virus in solution by more than 90 percent.

Another research group at the Georgia Institute of Technology used a similar approach to destroy the virus before it enters the cell. The method was tested in live animals, improving the symptoms of hamsters infected with COVID-19. The treatment also worked on mice infected with influenza, and the researchers believe it could be effective against 99 percent of all existing influenza strains.

As European, U.S., and U.K. regulators have given their stamp of approval for the first-ever CRISPR-based drug to treat patients, who is to say we wont see another CRISPR-drug hitting this milestone in the near future.

And apart from the diseases mentioned, CRISPR is also being studied to treat other conditions like vision and hearing loss. In blindness caused by mutations, CRISPR gene editing could eliminate mutated genes in the DNA and replace them with normal versions of the genes. Researchers have also demonstrated how getting rid of the mutations in the Atp2b2 and Tmc1 genes helped partially restore hearing.

However, one of the biggest challenges to turn CRISPR research into real cures is the many unknowns regarding the potential risks of CRISPR therapy. Some scientists are concerned about possible off-target effects as well as immune reactions to the gene-editing tool. But as research progresses, scientists are proposing and testing a wide range of approaches to tweak and improve CRISPR in order to increase its efficacy and safety.

Hopes are high that CRISPR technology will soon provide a way to address complex diseases such as cancer and AIDS, and even target genes associated with mental health disorders.

New technologies related to CRISPR research:

This article was originally published in June 2018, and has since been updated by Roohi Mariam Peter.

Read more here:
Seven diseases that CRISPR technology could cure - Labiotech.eu

Recommendation and review posted by Bethany Smith

CRISPR Therapeutics to Present at the American Society of Gene & Cell Therapy (ASGCT) 2024 Annual Meeting – GlobeNewswire

April 6th, 2024

ZUG, Switzerland and BOSTON, April 01, 2024 (GLOBE NEWSWIRE) -- CRISPR Therapeutics(Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, today announced an oral presentation at the American Society of Gene & Cell Therapy (ASGCT) 2024 Annual Meeting, taking place May 7 11, 2024, in Baltimore, MD and virtually.

Title: Development of an In Vivo Non-Viral Ocular Editing Platform and Application to Potential Treatments for Glaucoma Session Type: In-Person Oral Presentation Session Title: Ophthalmic and Auditory: Delivery Innovations Abstract Number:87 Location: Room 318 323 Session Date and Time: Wednesday, May 8, 2024, 1:30 p.m. 3:15 p.m. ET

Abstracts will be released to the public on April 22, 2024, at 4:30 p.m. ET at https://annualmeeting.asgct.org/. The data are embargoed until 6:00 a.m. ET on the presentation day, Wednesday May 8, 2024. A copy of the presentation will be available at http://www.crisprtx.com once the presentation concludes.

About CRISPR Therapeutics Since its inception over a decade ago, CRISPR Therapeutics has transformed from a research-stage company advancing programs in the field of gene editing, to a company with a diverse portfolio of product candidates across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine, cardiovascular and rare diseases. The Nobel Prize-winning CRISPR science has revolutionized biomedical research and represents a powerful, clinically validated approach with the potential to create a new class of potentially transformative medicines. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic partnerships with leading companies including Bayer and Vertex Pharmaceuticals. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Boston, Massachusetts and San Francisco, California, and business offices in London, United Kingdom. To learn more, visit http://www.crisprtx.com.

Investor Contact: Susan Kim +1-617-307-7503 susan.kim@crisprtx.com

Media Contact: Rachel Eides +1-617-315-4493 rachel.eides@crisprtx.com

Read more:
CRISPR Therapeutics to Present at the American Society of Gene & Cell Therapy (ASGCT) 2024 Annual Meeting - GlobeNewswire

Recommendation and review posted by Bethany Smith

First cardiac bioimplants for the treatment of patients with myocardial infarction using umbilical cord stem cells – EurekAlert

April 6th, 2024

image:

Surgery team ICREC-IGTP

Credit: IGTP

The promising results obtained in a clinical trial with a pioneering advanced therapy drug named PeriCord, which aims to repair the heart of patients who have suffered a heart attack, confirm the feasibility of new therapies based on the application of stem cells and tissue engineering to promote the regeneration of damaged tissues.

This new medicine, derived from umbilical cord and pericardium stem cells from tissue donors, is a world-first tissue engineering product (a type of advanced therapy combining cells and tissues optimised in the laboratory). The drug is applied in patients undergoing coronary bypass, utilising the procedure to repair the scar in the heart area affected by the infarction, which has lost the ability to beat when blood flow stopped.

Thefirst interventionof this new therapy was almost 4 years ago, resulting from a collaboration between the ICREC Group (Heart Failure and Cardiac Regeneration) at Germans Trias i Pujol Research Institute (IGTP) and Banc de Sang i Teixits (BST). Following its success, a study was initiated to demonstrate its clinical safety. The study included 12 coronary bypass candidates, 7 treated with bioimplants and 5 without, to compare the outcomes.

Dr Antoni Bays, ICREC researcher and first author of the article:"This pioneering human clinical trial comes after many years of research in tissue engineering, representing a very innovative and hopeful treatment for patients with a heart scar resulting from a heart attack", referring to PeriCord.

While the current study aimed to demonstrate the safety of this new drug in the context of myocardial infarction, its positive outcomes have shown that PeriCord possesses other exceptional properties. It has proven to be a medicine with excellent biocompatibility, drastically minimising the risk of rejection and ensuring perfect tolerance by the body. Additionally, it has anti-inflammatory properties, paving the way for broader applications in pathologies involving inflammation."Its potential could be much wider; we believe it can be a valuable tool for modulating inflammatory processes", explains Dr Sergi Querol, head of the Cellular and Advanced Therapies Service at BST.

Severe but stable patients

The patients included in the therapy are individuals who have suffered a heart attack and have reduced quality and life expectancy. The bypass ensures blood circulation in the area, and the bioimplant goes a step further to stimulate the scar, initiating cellular mechanisms involved in tissue repair.

"Voluntarily provided substances of human origin are used, both in terms of multi-tissue donor pericardial tissue and mesenchymal stem cells from umbilical cord donors at the birth of a baby", explains Querol. It is very gratifying to think that"thanks to this and the donors, we provide a new therapeutic tool that can improve a patient's quality of life", he adds.

PeriCord consists of a membrane that comes from the pericardium of a tissue donor, which BST has decellularised and lyophilised. It has then been recellularised with these umbilical cord stem cells.

Once in the operating theatre, surgeons attach the laboratory-generated bioimplant to the affected area of the patient's heart. After a year, the implanted tissue adheres and adapts perfectly to the structure of the heart, covering the scar left by the heart attack.

Randomized controlled/clinical trial

People

Implantation of a double allogeneic human engineered tissue graft on damaged heart: insights from the PERISCOPE phase I clinical trial

14-Mar-2024

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Original post:
First cardiac bioimplants for the treatment of patients with myocardial infarction using umbilical cord stem cells - EurekAlert

Recommendation and review posted by Bethany Smith

What people should know about stress, according to a doctor – Yahoo Singapore News

April 6th, 2024

Sign up for CNNs Stress, But Less newsletter.Our six-part mindfulness guide will inform and inspire you to reduce stress while learning how to harness it.

There is no doubt that stress is a part of everyday life, but too much can have detrimental impacts on peoples physical and mental health.

I wanted to delve more into depth about the health impacts of stress during National Stress Awareness Month. What does stress do to the body? When does it become a problem, and what are some ways to cope with it? And what can people do with stressors such as a hard job or caregiving responsibilities that cant just go away?

To help us answer these questions, I had a conversation with CNN wellness expert Dr. Leana Wen. Wen is an emergency physician and adjunct associate professor at George Washington University. She previously served as Baltimores health commissioner.

CNN: What does stress do to a persons body?

Dr. Leana Wen: When people experience a perceived threat, a variety of hormones are released that make the heart beat faster and increase blood pressure and blood sugar. These hormones also divert energy away from other parts of the body, such as the immune system and digestive system. These are evolutionary adaptations that once helped people to respond to situations such as predators chasing after them. Such fight or flight responses are normal and may be helpful in modern-day life. For instance, they could help an athlete with a faster performance or a student with staying up to study for an exam.

The problem arises when the bodys stress response is continuous. A perpetual state of fight or flight could lead to many chronic problems. Individuals could experience anxiety and depression, and other mental health ailments. They could also have headaches, muscle tension, abdominal pain, sleep disturbances, decreased immunity to infections, and problems with memory and concentration. Chronic stress has also been linked to increased likelihoods of high blood pressure, diabetes, heart attack and stroke.

Story continues

CNN: Everyone experiences stress, so when does it become a problem?

Wen: Its natural for people to experience stress to discrete stressful events (those that have a clear onset such as the birth of a child, starting of a new job, a divorce or the death of a loved one) that happen in their lives. The problem is when stress becomes a chronic state of being.

Warning signs to look out for include signs or symptoms of mental health concerns or physical manifestations of stressfor instance, if someone starts having new heart palpitations, abdominal pain or headaches. In addition, some people may attempt to cope with stress by using alcohol or drugs. A change in substance use could be a red flag to look for underlying stressors.

People should also ask themselves if stress is negatively affecting their function at home, at work and with their friends. Someone who finds themselves unusually irritable and is lashing out at loved ones and colleagues may also be doing so because of excessive stress.

CNN: Why should we be aware of excessive stress and try to reduce it as a health priority?

Wen: We can think of stress as something in our lives that is modifiable, just like high blood pressure or high blood sugar. The stressor itself may not be able to be changed, just as we cannot change our genetic predisposition to hypertension or diabetes. However, our reaction to it is within our control. And its our reaction to the stressor that determines our health outcomes. If stress has detrimental effects on our health, just as high blood pressure and diabetes do, then we can and should look for ways to reduce these effects.

CNN: What are some ways we can cope with stress?

Wen: First, its important to clarify that there are good and bad ways to cope with stress. Some people may turn to these not-so-good ways because it may help them feel better in the short-term, but there are real risks. I mentioned drinking alcohol and using drugsobviously, these are not healthy coping strategies. Neither are binge-eating or smoking.

I think its really important to be self-aware. Be honest with yourself: When you have faced stressful situations in the past, have you turned to these unhealthy ways to cope? If so, be on the lookout and work to prevent these behaviors during stressful times.

Also, try to anticipate when there will be stressful situations. Is there a big deadline at work coming up? A family gathering that is likely to elicit negative emotions? A difficult conversation with a loved one? Knowing that a stressful event may occur can help you anticipate your reaction and plan accordingly.

I advise, too, that people make a list of stress relief techniques that have worked for them in the past. And try new techniques. Deep breathing exercises are something everyone can try and help both in the moment of the stressful encounter and after, for example, as is mindfulness meditation.

Im also a big fan of exercise. There is excellent scientific evidence that exercise is very effective at managing stress. Exercise reduces stress hormones and increases endorphins, which are feel-good neurotransmitters that can relax the body and improve mood.

CNN: What is your advice for people who have stressors in their livessuch as a hard job or caregiving responsibilitiesthat cant easily go away?

Wen: This is really hard, because of course it would be ideal to address the stressors themselves. But many people have stressful situations that they cant change.

It helps to be up front about that and acknowledge that changing the situation is not in your control. What is in your control, though, is your reaction to the situation.

Here is where self-awareness and self-care are so important. Learn to recognize when you are feeling especially stressed. Perhaps you feel tension in your neck and back muscles, or you have abdominal cramps or jitters. These are the times to practice deep breathing, meditation and other exercises that help you in the short-term.

For both short- and long-term benefit, its essential to make time for self-care. By that, I mean activities that you enjoy and that can take your mind off the stressful life situations. These could include taking a walk with a good friend, working in the garden, playing with your pets, reading a good book or otherwise participating in activities you enjoy. Think of the time you are putting aside for yourself as a kind of therapy; stress can make you unhealthy, so this is your way of giving yourself treatment to offset that stress.

Along those lines, knowing that stress is one factor that can impact your well-being, work to maximize the other aspects that contribute to overall health. Try to get adequate, restful sleep. Aim to eat healthy, whole foods and reduce your consumption of ultra-processed products. Make sure other chronic medical conditions, such as high blood pressure, are being treated. And do not wait to seek help from your mental health or primary care provider if the stress you are experiencing is leading to continuing mental health or physical distress.

For more CNN news and newsletters create an account at CNN.com

Go here to see the original:
What people should know about stress, according to a doctor - Yahoo Singapore News

Recommendation and review posted by Bethany Smith

Pharmac seeking bids from suppliers to fund another type of hormone replacement therapy – New Zealand Doctor Online

April 6th, 2024

Pharmac Te Ptaka Whaioranga has issued a request for proposals (RFP) asking suppliers to bid for the supply of oestradiol gel in New Zealand.

Pharmac is looking to fund a new type of oestradiol treatment without restrictions, says Dr David Hughes, Pharmacs Director Advice and Assessment/Chief Medical Officer.

In the past three years, the supply issues for oestradiol patches has caused stress and frustration for New Zealanders. Demand has more than doubled - growing from 1.2 million patches dispensed in 2020/21 to over 3 million patches in 2022/23.

Our clinical advisors have told us that funding another oestradiol product would be useful because demand is increasing, and we are continuing to experience global supply issues for oestradiol patches. We know that some people would use the gel if its funded, and this could relieve some of the stress on the supply of patches.

Oestradiol is used by 85,000 people each year for the treatment of a range of conditions including, menopause, osteoporosis, and gender affirming health care. It is most often used as a patch placed on the skin, but it is also available as a tablet.

We want to make sure people get the treatment they need, and which can be funded from Pharmacs fixed budget, so were keen to hear from suppliers about what they can offer, says Dr Hughes.

Dr Linda Dear, a menopause specialist says, Its wonderful to hear that another step is being taken towards giving perimenopausal and menopausal New Zealanders fully funded access to oestradiol (estrogen) gels.

This will provide a much-needed alternative, so people are no longer solely reliant on the patches as the only funded transdermal option available. Having gels as an alternative will ease the pressure of the supply issue which has had an impact on New Zealanders using the treatments, pharmacists, and prescribing doctors alike. My hope is that we dont have to wait too much longer to access this important therapy.

Pharmacs job is to assess and prioritise which treatments will deliver the best possible health outcomes for New Zealanders from the available budget, says Dr Hughes.

"Once this RFP closes, an evaluation committee will meet to consider the bids received. We will also seek advice from our clinical advisors. As this activity progresses, well share more information with the public.

Read the original here:
Pharmac seeking bids from suppliers to fund another type of hormone replacement therapy - New Zealand Doctor Online

Recommendation and review posted by Bethany Smith

Genomic insights into familial adenomatous polyposis: unraveling a rare case with whole APC gene deletion and … – Nature.com

March 29th, 2024

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder resulting from germline mutations in the APC gene. The APC gene, comprising 15 exons and encoding a protein with 2843 amino acids, is implicated in ~80% of FAP cases1. Extensive genetic analysis has revealed germline variants in FAP patients, and most APC mutations are found in the 5 half of the coding region. Genotypephenotype correlations have been reported for small-nucleotide alterations, including frameshift and nonsense mutations2,3. Large genomic deletions and duplications have been identified using multiplex ligation-dependent probe amplification (MLPA)4. Whole-genome array comparative genomic hybridization (aCGH) was used to identify a large deletion involving the middle portion of the long arm of chromosome 55. Here, we report a case of an FAP patient with intellectual disability that was attributed to a large deletion involving 5q22.2.

The proband was a 28-year-old female who was referred to the emergency hospital with acute abdominal pain. Computed tomography (CT) demonstrated perforation of the descending colon, multiple colorectal polyps, multiple liver metastases and lymph node swelling. She underwent left hemicolectomy, and the subsequent histological diagnosis was moderately differentiated adenocarcinoma (pT4a, pStage IVa). Chemotherapy was selected for treatment of the residual metastasis. Colonoscopy revealed advanced colon cancer with multiple adenomatous polyps (>100). Head CT revealed an osteoma in her skull, and the phenotype was subsequently defined as Gardners syndrome.

The patient had slight intellectual disability without developmental delay or neurogenic abnormalities. She and her mother requested comprehensive genomic panel (CGP) analysis (OncoGuideTM NCC oncopanel, Sysmex, Hyogo, Japan) of surgically resected colon cancer tissue after providing informed consent. This test can detect mutations in 124 genes and differentiate between germline and somatic mutations. The pathogenic mutations detected were KRAS G13D, PIC3CA H1047R, and TP53 M169fs*2, but no targeted therapy was recommended by the expert panel. No germline findings were reported, but whole APC gene deletion was suspected due to the low amplicon depth of the APC gene in both the tumor tissue and blood samples (Fig. S1).

According to her familial history (Fig. 1), her mother (II-3) was treated for sporadic colon cancer. She refused genetic testing due to receiving cancer chemotherapy. Her son (IV-1), whose intelligence was slightly low, had a single-parent history because his father was not identified.

The arrow indicates the patients who underwent genetic counseling. A closed circle indicates an individual with colorectal cancer. Colorectal polyposis was observed in the proband (III-1) but not in her ancestors.

After genetic counseling, aCGH (GenetiSure Dx Postnatal Assay, Agilent, Tokyo, Japan) was performed for further genetic testing. Notably, aCGH revealed the loss of chromosome 5 (chr5) q22.1-q22.2 (Fig. 2), the loss of chr3 p24.1-p23, and the gain of chr15 q15.3. The chr5 deletion included the entire APC gene (chr5:112043195-112181936 in GRCh37) located at 5q22.2 (Fig. S2), according to the Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources (DECIPHER, https://www.deciphergenomics.org).

A heterozygous 5q22 deletion was detected. The minimal and maximal deletion positions in GRCh37 (start_stop) were 111143360_112213143 and 111118900_112239978, respectively.

This case in which the entire APC gene was deleted, as determined by aCGH, is rare. Chromosome 5p22.1-22.2 deletion causes 1Mb of heterozygous loss, including the APC gene, which was reported as a cytogenetically detected deletion in previous reports. Previously, karyotyping and fluorescence in situ hybridization were used to detect large submicroscopic genomic deletions, and aCGH was used to detect high-resolution copy number variants in whole chromosomes6. aCGH is sensitive and comprehensive, allowing detection of multiple variations, and annotations by specialists are needed. DECIPHER catalogs common copy number changes, enabling the identification of potentially pathogenic variants. aCGH can also be used for sequencing targeted genes. For FAP patients, germline APC variants are identified by direct sequencing using next-generation sequencing (NGS) and MLPA5. Sequencing has been used to detect APC gene variants, but ~20% of FAP patients do not carry these variants. MLPA is useful for detecting whole or large APC gene copy number variants in mutation-negative FAP patients. There are several case reports in which germline variants of FAP were examined via aCGH7,8,9,10.

Our young patient with advanced colon cancer derived from multiple colorectal polyposis was diagnosed with FAP according to the clinical features. A CGP was performed using NGS for cancer precision medicine in this patient. Because metastatic colon cancer is treated by chemotherapy, somatic genomic analysis with CGP was also conducted to determine the optimal chemotherapy regimen. Next, we used NGS to determine the sequence of 100bp amplicons of 124 cancer-related genes from cancer tissue and peripheral blood. A large APC deletion was not detected by this targeted sequence, although both the somatic and germline amplicon depths of the APC gene were slightly low. A large number of APC variants have already been deposited in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/). For several FAP patients in which germline APC variants were not found, investigations of copy number variations have been performed. The genotypephenotype correlation of patients with chromosome 5q deletions has been discussed10. A classical FAP phenotype is associated with a mutation in codons 1681250 or codons 14001580. A severe phenotype is caused by a mutation in codons 12501464. A more attenuated form is associated with mutations in three regions: the 5 region of the APC gene, the alternative splicing region in exon 9, and the extreme 3 end of the gene11.

Whole or partial APC gene deletions can be detected with recently developed genetic techniques9,10,12. MLPA and aCGH are candidates for confirming large deletions or duplications, and the latter genetic test was chosen for our patient. In our patient, two chromosomal losses and one gain were detected. The advantage of chromosomal analysis is that it can reveal unexpected genetic changes even in separate chromosomes. The CGH database includes some patients with large deletions in chromosomal region 5q22, including the APC gene. In a very recent case report, aCGH was utilized to identify a large 19.85Mb deletion12. A case series with a literature review described a patient with intellectual disability and a colon neoplasm with an interstitial deletion of 5q identified by aCGH. Colorectal cancers are observed in some patients with 5q deletions, yet examination of colorectal polyposis in this context is limited. Among the primary dysmorphisms and symptoms linked to 5q deletions, the predominant manifestation identified in the analysis of 12 patients was mental retardation12. The cases documented in both the literature and the DECIPHER database are characterized by common clinical features, including predisposition to cancer, intellectual disability, and neurodevelopmental delay. Patients with these congenital changes should undergo genetic testing, including G-band, fluorescence in situ hybridization (FISH), and aCGH. aCGH offers high resolution, allowing for the detection of changes at the chromosomal level. This high sensitivity is particularly valuable when conventional methods, such as karyotyping or FISH, may not provide detailed information about genomic alterations. Moreover, this approach allows researchers and clinicians to explore potential genetic factors beyond the well-known APC genes. In the near future, long-read sequencing of large deletions may enable us to obtain detailed genomic information13. Additional clinical information is needed to establish the genotypephenotype correlations associated with the 5q22.2 deletion that includes the whole APC gene. The published cases have raised the question of whether whole APC deletion induces colorectal polyposis. Casper et al. reported a case of Gardner syndrome attributable to a substantial interstitial deletion of chromosome 5q, offering a comprehensive review of published cases9. Until 2014, 16 patients with FAP resulting from chromosome 5q deletions were documented, with all but one patient presenting with classic adenomatous polyposis rather than the profuse form. Most of these deletions were de novo alterations, consistent with our reported case in which the patients mother (II-3) exhibited sporadic colon cancer without polyposis. In the familial lineage (Fig. 1), our patients son (IV-1) carried a deletion in the 5q22.1-22.2 region, mirroring the genomic alteration of his mother (III-1). However, the genetic inheritance pattern of this large deletion is unclear. Meticulous follow-up of the young boy is important for addressing this issue.

In conclusion, this study describes a rare FAP patient characterized by a large deletion of chromosome 5q22.1-22.2 identified through comprehensive genomic analysis. The genetic variant was suspected by CGP and eventually identified by aCGH. These findings emphasize the importance of advanced genetic techniques in identifying complex genomic variations and suggest a need for additional research to elucidate the specific features associated with whole-APC gene deletions.

Link:
Genomic insights into familial adenomatous polyposis: unraveling a rare case with whole APC gene deletion and ... - Nature.com

Recommendation and review posted by Bethany Smith

Genetic Analysis Market Size to Attain Around USD 23.60 BN by 2033 – BioSpace

March 29th, 2024

The global genetic analysis market was evaluated at USD 10.55 billion in 2023 and is expected to attain around USD 23.60 billion by 2033, growing at a CAGR of 8.39% from 2024 to 2033. The increasing demand for genetic testing services is driving growth within the genetic analysis market.

Market Overview

The genetic analysis market is experiencing significant transformation due to advances in genetic technology, which are fundamentally changing perceptions and practices within the healthcare industry. At the heart of this transformation lies the process of genetic analysis, which involves the examination of DNA samples to identify mutations that may influence disease susceptibility or treatment response. This analysis is pivotal for understanding the structure and function of genes, with techniques such as gene cloning playing a crucial role in isolating and replicating specific genes for detailed examination.

Get report sample pages@ https://www.precedenceresearch.com/sample/3922

One notable aspect of genetic analysis is its diverse clinical applications. It serves as a diagnostic tool, aiding in the confirmation of diagnoses in symptomatic individuals, while also facilitating the monitoring of disease prognosis and treatment response. Additionally, genetic analysis enables predictive or predisposition testing, allowing for the identification of individuals at risk of developing certain diseases before symptoms manifest.

The emergence of predictive genetic testing is creating new market opportunities, as it enables proactive disease prevention strategies and early interventions. As perceptions regarding genetic testing continue to evolve, the market for genetic analysis is expected to witness sustained growth, driven by its potential to revolutionize patient care and improve health outcomes.

Key Insights

Get full access of this report@ https://www.precedenceresearch.com/checkout/3922

North America to sustain its position in the upcoming years with the U.S. being largest contributor

In 2023, North America emerged as the dominant force in the genetic analysis market, particularly in the United States. The US showcased a robust infrastructure with 200 laboratories actively conducting 37,124 clinical tests, underscoring the region's significant investment and adoption of genetic analysis technologies. Notably, 29 laboratories specialized in whole exome sequencing (WES), while 17 laboratories focused on whole genome sequencing (WGS), indicating a wide array of genetic testing capabilities available within the country.

The United States exhibits a proactive approach towards healthcare, as evidenced by mandatory newborn screening programs targeting a specific set of genetic diseases. Although the exact set of diseases screened may vary from state to state, the emphasis remains on conditions where early diagnosis is crucial for effective treatment or prevention strategies. This regulatory framework underscores the importance placed on leveraging genetic analysis for proactive healthcare management and disease prevention initiatives.

Beyond clinical applications, genetic analysis in North America extends to ecological and environmental contexts. The presence of invasive species such as Phragmites australis subsp. australis poses ecological challenges across multiple regions. The co-occurrence of this invasive subspecies with native counterparts and instances of hybridization necessitates precise differentiation methods for effective management strategies. Genetic analysis plays a pivotal role in distinguishing between phragmites subspecies or haplotypes, facilitating targeted management efforts to mitigate ecological harm and preserve native ecosystems.

Asia Pacific to witness lucrative opportunities in the upcoming years

Asia Pacific emerges as a pivotal region poised for substantial growth in the genetic analysis sector, driven by dynamic developments in genetic counselling and genome mapping initiatives. Forecasts indicate that Asia Pacific will experience the fastest growth rate in the genetic analysis market during the forecast period, underscoring the region's significance in shaping the future of genetic healthcare services.

A recent milestone in the region's genetic counselling landscape is the establishment of the Professional Society of Genetic Counsellors in Asia (PSGCA). Formed as a special interest group of the Asia Pacific Society of Human Genetics, PSGCA aims to spearhead the advancement and integration of the genetic counselling profession across Asia. With a vision to become the premier organization driving genetic counselling mainstream adoption in the region, PSGCA endeavors to ensure equitable access to genetic counselling services for individuals. Its mission centers on elevating standards of practice, curriculum, research, and continuing education to promote quality genetic counselling services throughout Asia.

The rapid evolution of genetic and genomic technologies has significantly transformed healthcare services in low- and middle-income countries (LMICs) across the Asia-Pacific region. Initially focused on population-based disease prevention strategies, genetic services have transitioned towards clinic-based and therapeutics-oriented approaches. Notably, the region's genetic diversity, exemplified by populous and genetically varied countries such as China, India, Japan, and Indonesia, positions them as prime candidates for genome mapping research endeavors.

How the genetic analysis market in Asia Pacific

Report Highlights

By Product

The reagents & kits segment asserted dominance in the genetic analysis market in 2023. DNA reagents play a pivotal role in various DNA-related processes and techniques, including sequencing, synthesis, cloning, and mutagenesis. These products encompass a diverse range, such as plasmids, buffers, labeling technology, columns, and comprehensive test kits utilized in DNA testing, including direct-to-consumer (DTC) genetic tests. While offering accessible information about the scientific basis of tests, the usage of DTC genetic tests carries inherent risks due to the absence of personalized guidance concerning the results.

The instruments segment emerged as the fastest-growing sector within the genetic analysis market. Core laboratory instruments constitute essential tools in genetic engineering research, facilitating precise and reliable experimentation. Polymerase Chain Reaction (PCR) machines, also known as thermal cyclers, stand as indispensable equipment in genetic engineering labs, enabling the amplification of specific DNA segments crucial for detailed analysis.

By Test

In 2023, the disease diagnostic testing segment emerged as the dominant force in the genetic analysis market. This segment specializes in identifying whether individuals harbor specific genetic diseases by detecting alterations in particular genes. While these tests excel at pinpointing gene mutations, they often fall short in determining disease severity or age of onset. Thousands of diseases stem from mutations in a single gene, making diagnostic testing pivotal in confirming or ruling out genetic diseases and chromosomal abnormalities. Frequently utilized during pregnancy or when symptomatic, diagnostic genetic testing offers crucial insights for accurate diagnosis and timely intervention.

The prenatal and newborn testing segment emerged as the fastest-growing sector in the genetic analysis market during the forecast period. Prenatal genetic testing provides prospective parents with vital information regarding potential genetic disorders in the fetus. Prenatal screening tests assess the likelihood of fetal aneuploidy and select disorders, while prenatal diagnostic tests definitively ascertain the presence of specific disorders. These tests, conducted on fetal or placental cells obtained through procedures like amniocentesis or chorionic villus sampling (CVS), play a pivotal role in informed decision-making during pregnancy.

Newborn screening, a subset of prenatal and newborn testing, comprises a set of laboratory tests performed on newborns to detect known genetic diseases. Typically conducted via a heel prick within the first few days of life, newborn screening enables early identification and intervention for treatable genetic conditions, thereby improving health outcomes. As the demand for early detection and preventive measures rises, the prenatal and newborn testing segment is poised for continued growth, bolstering the comprehensive landscape of genetic analysis.

By Technology

In 2023, the real-time PCR system segment emerged as the dominant force in the genetic analysis market. Real-time PCR (RT-PCR) systems offer unparalleled capabilities for quantitative genotyping and detection of single nucleotide polymorphisms (SNPs), allelic discrimination, and genetic variations even in samples with minimal mutation carriers. Multiplex PCR systems, a subset of RT-PCR, are gaining prominence, particularly in plant/microbe associations, where standard PCR methods prove inadequate. Multiplex RT-PCR facilitates the identification of multiple genes through the utilization of fluorochromes and analysis of melting curves, providing enhanced accuracy and efficiency in genetic analysis.

The next-generation sequencing (NGS) segment emerged as the fastest-growing sector in the genetic analysis market. NGS technology revolutionizes DNA sequencing and RNA sequencing and variant/mutation detection by enabling high-throughput sequencing of hundreds to thousands of genes or whole genomes within a short timeframe. The sequence variants/mutations detected by NGS hold profound implications for disease diagnosis, prognosis, therapeutic decision-making, and patient follow-up, paving the way for personalized precision medicine initiatives.

By Application

In 2023, the infectious diseases segment asserted dominance in the genetic analysis market, offering molecular genetic tests capable of identifying common viruses or bacteria responsible for respiratory infections and infectious diarrhea. These tests, conducted on samples collected from the nose and throat or a single stool sample, facilitate rapid and accurate diagnosis, enabling timely treatment and containment of infectious outbreaks.

The genetic diseases segment emerged as the fastest-growing sector in the genetic analysis market during the forecast period. The extent to which genes contribute to diseases varies, presenting opportunities for advancements in understanding genetic mechanisms underlying various conditions. This progress facilitates the development of early diagnostic tests, novel treatments, and preventive interventions to mitigate disease onset or severity.

By End Use

In 2023, the research & development laboratories segment emerged as the dominant force in the genetic analysis market, actively driving advancements in genetic disease study and testing technology. These laboratories are pivotal in enhancing clinical patient care by conducting rigorous research and development activities aimed at improving test strategies and introducing novel genetic tests. Board-certified directors and genetic counsellors collaborate closely with laboratory supervisors and technologists to ensure the delivery of accurate and reliable results within stipulated timelines. With a focus on meeting stringent validation standards, approved tests undergo thorough evaluations of methodology and clinical utility. Research programs within these laboratories leverage collective expertise to propel the field of genetics and genetic testing forward.

The diagnostic centers segment is poised for significant growth in the genetic analysis market during the forecast period. Diagnostic centers offer a comprehensive range of testing services crucial for diagnosing diverse medical conditions. By providing accurate and informed diagnoses, diagnostic centers enable physicians to develop effective treatment plans, ultimately enhancing patient outcomes. Leveraging advanced diagnostic technologies and techniques, these centers play a vital role in identifying underlying causes of diseases, monitoring disease progression, and devising personalized treatment approaches. Collaborating with healthcare providers like primary care physicians, specialists, and hospitals, diagnostic centers ensure accurate and timely diagnoses across a spectrum of medical conditions, reinforcing their indispensable role in modern healthcare delivery.

Market Dynamics

Driver: Advances in Genetic Sequencing and Gene Therapy

Significant strides in genetic sequencing, human genome analysis, and medical genetics have revolutionized disease understanding, diagnostic accuracy, and drug development targets. A pivotal breakthrough in medical genetics is the emergence of gene therapy, which involves modifying or replacing genes to treat or prevent diseases. Already applied successfully in treating conditions like inherited blindness and severe combined immunodeficiency (SCID), gene therapy is poised to expand its impact further.

Future projections indicate that gene therapy will play an increasingly vital role in medical genetics, offering treatments for previously untreatable diseases. This trajectory is expected to fuel the growth of the genetic analysis market, as the demand for advanced genetic testing and analysis escalates to support the development and implementation of gene therapy treatments.

Restraint: Privacy Concerns in Genetic Analysis

Privacy concerns poses a major challenge in the genetic analysis domain due to the inherent uniqueness of genomic data, hindering true anonymization efforts. Additionally, security measures are crucial to restrict access to data based on authorized clearance levels, safeguarding against unauthorized breaches. Confidentiality emerges as a key ethical consideration, dictating the responsible sharing of genetic data. These privacy concerns, among others, including consent and data ownership, serve as significant restraints in the genetic analysis market. Addressing these challenges effectively is essential to ensure ethical practices and foster trust among stakeholders, thereby mitigating the barriers to market growth.

Opportunity: Integration of Artificial Intelligence in Genetic Analysis

The integration of artificial intelligence (AI) is revolutionizing clinical genetics, offering unprecedented opportunities for advancement. AI algorithms possess the capability to analyse vast volumes of genetic data rapidly and accurately, facilitating more precise diagnoses and tailored treatment plans. Furthermore, AI empowers predictive analysis of disease risk, enabling the development of proactive disease prevention strategies. In genetic engineering and gene therapy research, AI serves as a powerful tool, aiding in hypothesis generation and experimental techniques. Leveraging AI, researchers can detect hereditary and gene-related disorders with greater efficiency.

Moreover, AI-driven developments hold immense promise for rational drug discovery and design, ultimately impacting humanity's well-being. As AI and machine learning (ML) technologies continue to drive innovation in drug development, genetics emerges as a prime beneficiary, with AI expected to influence every facet of the human experience. This presents a compelling opportunity for the genetic analysis market to capitalize on AI-driven advancements and propel transformative growth.

Recent Developments

Key Players in the Clinical Trials Market

Segments Covered in the Report

By Product

By Test

By Technology

By Application

By End-use

By Geography

Get full access of this report@ https://www.precedenceresearch.com/checkout/3922

Contact Us

Call: USA: +1 650 460 3308 | IND: +91 87933 22019 | Europe: +44 2080772818

Email: sales@precedenceresearch.com

Here is the original post:
Genetic Analysis Market Size to Attain Around USD 23.60 BN by 2033 - BioSpace

Recommendation and review posted by Bethany Smith

Bill Introduced in Minnesota Would Increase Access To Genetic Testing – PR Newswire

March 29th, 2024

Susan G. Komen Commends Bill Introduction; Urges Quick Passage

ST. PAUL, Minn., March 28, 2024 /PRNewswire/ --Susan G. Komen, the world's leading breast cancer organization, applauds Representative Patty Acomb (D-Minnetonka) for introducing legislation that would eliminate financial barriers to clinically appropriate genetic testing, as well as the recommended screenings based on the results of that testing.

In Minnesota, more than 5,480 people will be diagnosed with breast cancer and 630 are expected to die of the disease in 2024 alone. In the U.S., 5-10% of breast cancers are related to a known inherited gene mutation. The lifetime risk of breast cancer increases 20-49% for women with moderate risk inherited gene mutations and 50% or more for women with high-risk inherited gene mutations.

HF 5050, introduced by Rep Acomb, eliminates the patient out-of-pocket costs for multi-gene panel testing for inherited gene mutations and evidence-based screenings, ensuring individuals have access to critical information regarding their lifetime cancer risk and recommended early detection and cancer surveillance.

"Passage of this legislation will allow patients to better understand their lifetime cancer risk and access to needed risk reduction and treatment strategies," said Molly Guthrie, Vice President of Policy and Advocacy at Susan G. Komen. "Individuals should have all information needed to make informed decisions about their healthcare without burdensome financial barriers."

Germline testing is a type of test that looks for inherited mutations that have been present in every cell of the body since birth. These tests are conducted via the collection and analysis of blood, saliva or cheek cells. Identification of inherited cancer risk can help guide decisions regarding recommended screenings for the early detection of cancer, personalized cancer treatments and risk-reducing medical treatments.

Studies have shown an estimated 83 percent of eligible patients that underwent multigene panel testing had changes to their medical management, including modifications in follow-up and chemotherapy strategy.

"This legislation will ensure patients have equitable access to information concerning their lifetime risk of cancer, allowing them to make key decisions regarding risk reducing strategies and recommended screenings for early detection," said Rep. Patty Acomb.

According to a 2020 American Association for Cancer Research Report, 65% of young white women with breast cancer were offered genetic testing, while only 36% of young Black women with breast cancer were offered the same test options. Additional studies show that minority patients were more likely to utilize genetic testing following a cancer diagnosis but less likely following a family history of cancer, resulting in a missed opportunity for mutation detection and cancer prevention for these patients.

About Susan G. KomenSusan G. Komen is the world's leading nonprofit breast cancer organization, working to save lives and end breast cancer forever. Komen has an unmatched, comprehensive 360-degree approach to fighting this disease across all fronts and supporting millions of people in the U.S. and in countries worldwide.We advocate for patients, drive research breakthroughs, improve access to high-quality care, offer direct patient support and empower people with trustworthy information. Founded by Nancy G. Brinker, who promised her sister, Susan G. Komen, that she would end the disease that claimed Suzy's life, Komen remains committed to supporting those affected by breast cancer today, while tirelessly searching for tomorrow's cures. Visit komen.org or call 1-877 GO KOMEN. Connect with us on social at http://www.komen.org/contact-us/follow-us/.

CONTACT: Amanda DeBard Susan G. Komen (972) 701-2131 [emailprotected]

SOURCE Susan G. Komen for the Cure

See the original post:
Bill Introduced in Minnesota Would Increase Access To Genetic Testing - PR Newswire

Recommendation and review posted by Bethany Smith

Genetic variation passed down through generations may influence cancer development – Baylor College of Medicine | BCM

March 29th, 2024

Genes affected by germline structural variation could conceivably influence cancer risk.

Researchers at Baylor College of Medicines Dan L Duncan Comprehensive Cancer Center and Human Genome Sequencing Center investigated the extent to which forms of genetic variation called germline or inherited structural variation (SV) influence gene expression in human cancers.

Structural variation is one type of genomic variation and can be beneficial, neutral or, if it affects functionally relevant regions of the genome, can seriously affect gene function and contribute to disease, including cancer, said corresponding author Dr. Chad Creighton, professor ofmedicineand co-director of cancer bioinformatics at theDan L Duncan Comprehensive Cancer Centerat Baylor.

Structural variations are larger differences in the genome that occur when a piece of DNA is duplicated, deleted, or switched around, which can impact genetic instructions encoded in DNA and affect the expression of nearby genes. Previous studies led by the researchers have shown that structural variations occurring in specific cell types, like breast cells, can strongly influence gene expression in ways that contribute to transforming a healthy breast cell into a cancer cell.

Its known that germline structural variation also can contribute to the molecular profile of cancers, Creighton said. Here we study the extent of its contribution. The study is published in Cell Reports Medicine.

The researchers worked with data developed by the Pan-Cancer Analysis of Whole Genomes consortium, which includes whole genome sequencing data from 2,658 cancers across 38 tumor types involving 20 major tissues of origin. The team integrated these data with RNA data to identify genes whose expression was associated with nearby germline structural variations.

We found most of the genes associated with germline structural variations would not necessarily have specific roles in cancer, but for some genes, the expression variation might be associated with other conditions, Creighton said.

At the same time, several genes affected by germline structural variation could conceivably contribute to cancer, for instance if these genes have an established cancer association or an association with patient survival.

This study shows that germline structural variation would represent a normal class of genetic variation passed down through generations and may play a significant role in cancer development. The researchers propose that the subset of genes with cancer-relevant associations arising in this study would represent strong candidates for further investigation on their value in genetic testing.

Fengju Chen, Yiqun Zhang and Fritz J. Sedlazeck also contributed to this work.

This study was supported by the National Institutes of Health grant P30CA125123.

By Ana Mara Rodrguez, Ph.D.

Follow From the Labs on X @BCMFromtheLabs and Instagram!

Read this article:
Genetic variation passed down through generations may influence cancer development - Baylor College of Medicine | BCM

Recommendation and review posted by Bethany Smith

Unusually mild case of AADC deficiency reveals new gene mutation – AADC News

March 29th, 2024

Genetic testing done for a 55-year-old woman diagnosed with an unusually mild case of AADC deficiency revealed a disease-causing gene mutation never before reported, according to researchers.

The newly identified mutation, while indeed found to be a cause of the patients genetic disease, still allowed for the relatively preserved function of the AADC protein. The researchers said in a case report that the increased protein function may be why the patients symptoms were mild.

Details were given in An attenuated, adult case of AADC deficiency demonstrated by protein characterization, which was published in the journal Molecular Genetics and Metabolism Reports. The work was funded in part by PTC Therapeutics, makers of the AADC deficiency gene therapy Upstaza (eladocagene exuparvovec).

The researchers said their approach in the womans case provided the molecular basis for the mild presentation of the disease, and added that the experience can also be useful for personalized therapeutic decisions in other mild AADC deficiency patients.

AADC deficiency is caused by mutations in the DDC gene, which provides instructions for making the eponymous AADC enzyme. This enzyme is needed to make brain signaling molecules, or neurotransmitters, like dopamine and serotonin. Abnormally low levels of these neurotransmitters in AADC deficiency lead to disease symptoms.

Most people with AADC deficiency who do not receive treatment have very little ability to move or speak on their own. In marked contrast to the typical picture of severe disease, this patient had only some cognitive abnormalities and occasionally experienced moments of weakness in her legs. Overall, her cognitive issues were fairly mild, and she was able to walk and ascend stairs without too much difficulty.

The patient reported that her siblings also had experienced cognitive issues, and that, as a child, she had sometimes experienced episodes where her eyes would roll upward when she was tired. With the benefit of hindsight, the researchers suspect these childhood episodes may have been oculogyric crises, a characteristic symptom of AADC deficiency.

The woman sought medical attention in her mid-50s because she was experiencing mood swings, and the episodes of weakness in her legs had been getting worse, leading to sudden falls.

Analyses of the fluid around the patients brain indicated low levels of dopamine and serotonin, consistent with a diagnosis of AADC deficiency.

Tests of her blood showed AADC enzyme activity was about 28% of whats considered normal which is low enough to qualify for AADC deficiency, but only just, given that healthy AADC carriers typically have activity of 35% to 40%.

Every individual has two copies of the DDC gene, with one inherited from each biological parent. AADC deficiency only develops if both copies are mutated. Carriers, meanwhile, have one mutated copy and one healthy copy and, as such, dont develop disease.

Genetic testing of this patient showed one of her DDC genes carried a mutation dubbed p.Arg347Gln, which has previously been reported to cause AADC deficiency. Her other copy of the gene carried another mutation, p.Glu227Gln, which has never been reported before.

To better understand the molecular basis for this patients unusually mild symptoms, the researchers conducted a series of tests to characterize this combination of mutations. The AADC enzyme normally functions as a dimer that is, two individual AADC enzymes join together to carry out the enzymes function.

The researchers found that when an AADC dimer contained two proteins both with the known disease-causing mutation p.Arg347Gln, the dimer had essentially no ability to function at all. By contrast, an AADC dimer with two enzymes carrying the novel p.Glu227Gln mutation had near-normal functionality. A dimer containing one enzyme with each mutation had about 75% of the activity of a normal AADC dimer.

Altogether these data suggest that these two mutations cause AADC deficiency that is characterized by comparatively high enzyme activity likely explaining why this patient had such mild symptoms.

After the diagnosis of AADC deficiency was confirmed, the patient was started on treatment with vitamin B6 (pyridoxine). She reported more energy and less fatigue after starting the treatment.

Interestingly, in the last few years, many previously undiagnosed or misdiagnosed patients have been identified as mild cases of AADC deficiency, expanding the phenotype [characteristics] of this neurotransmitter disease, the researchers wrote.

Read more:
Unusually mild case of AADC deficiency reveals new gene mutation - AADC News

Recommendation and review posted by Bethany Smith

China Genetic Testing Analysis Report 2024: Market to Reach $14.9 Billion by 2032 from $4.3 Billion in 2023, Driven … – PR Newswire

March 29th, 2024

DUBLIN, March 27, 2024 /PRNewswire/ -- The"China Genetic Testing Market Report by Test Type, Disease, Technology, Service Provider, Testing Sample 2024-2032" report has been added toResearchAndMarkets.com's offering.

The China genetic testing market size reached US$ 4.3 billion in 2023. The market is projected to reach US$ 14.9 billion by 2032, exhibiting a growth rate (CAGR) of 14.9% during 2023-2032.

Genetic testing is becoming popular in China. It may benefit many different interest groups, such as individuals and families with a history of genetic disorder, pregnant women, employers, and health or life insurance. This market is currently driven by a number of factors such as rising awareness regarding the benefits of genetic testing, availability of direct to consumer tests and increasing incidences of genetic disorders.

Over the past few years, there has been a significant rise in the awareness levels regarding the benefits of genetic testing in China. Genetic testing provides various technologies that help in the early detection of various chronic diseases and ensures its treatment and prevention. Moreover, a rise in the availability of Direct to consumer tests (DTC) which has increased the convenience and accessibility of such tests is also creating a positive impact in the growth of the market.

Moreover, In October, 2015, China announced that the iconic one-child policy had finally been replaced by a universal two-child policy. This is expected to increase the number of babies born each year and create a positive impact on the demand of the new born genetic testing segment. Other major factors that are expected to drive this market include growing middle class, aging population, and expanding healthcare system.

This report provides a deep insight into the China genetic testing market covering all its essential aspects. This ranges from macro overview of the market to micro details of the industry performance, recent trends, key market drivers and challenges, SWOT analysis, Porter's five forces analysis, value chain analysis, etc. This report is a must-read for entrepreneurs, investors, researchers, consultants, business strategists, and all those who have any kind of stake or are planning to foray into the China genetic testing industry in any manner.

Key Questions Answered in This Report

Competitive Landscape

Key Market Segmentation:

Breakup by Test Type:

Breakup by Disease:

Breakup by Technology:

Breakup by Service Provider:

Breakup by Testing Sample:

For more information about this report visit https://www.researchandmarkets.com/r/ob8wjd

About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

Media Contact:Research and Markets Laura Wood, Senior Manager [emailprotected] For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900 U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716

Logo: https://mma.prnewswire.com/media/539438/Research_and_Markets_Logo.jpg

SOURCE Research and Markets

Read the original here:
China Genetic Testing Analysis Report 2024: Market to Reach $14.9 Billion by 2032 from $4.3 Billion in 2023, Driven ... - PR Newswire

Recommendation and review posted by Bethany Smith

UMass Amherst Engineers Create Bioelectronic Mesh Capable of Growing with Cardiac Tissues for Comprehensive … – Diagnostic and Interventional…

March 29th, 2024

March 25, 2024 A team of engineers led by the University of Massachusetts Amherst and including colleagues from the Massachusetts Institute of Technology (MIT) recently announced in the journalNature Communicationsthat they had successfully built a tissue-like bioelectronic mesh system integrated with an array of atom-thin graphene sensors that can simultaneously measure both the electrical signal and the physical movement of cells in lab-grown human cardiac tissue. In a research first, this tissue-like mesh can grow along with the cardiac cells, allowing researchers to observe how the hearts mechanical and electrical functions change during the developmental process. The new device is a boon for those studying cardiac disease as well as those studying the potentially toxic side-effects of many common drug therapies.

Cardiac disease is the leading cause of human morbidity and mortality across the world. The heart is also very sensitive to therapeutic drugs, and the pharmaceutical industry spends millions of dollars in testing to make sure that its products are safe. However, ways to effectively monitor living cardiac tissue are extremely limited.

In part, this is because it is very risky to implant sensors in a living heart, but also because the heart is a complex kind of muscle with more than one thing that needs monitoring. Cardiac tissue is very special, saysJun Yao, associate professor of electrical and computer engineering in UMass Amhersts College of Engineering and the papers senior author. It has a mechanical activitythe contractions and relaxations that pump blood through our bodycoupled to an electrical signal that controls that activity.

But todays sensors can typically only measure one characteristic at a time, and a two-sensor device that could measure both charge and movement would be so bulky as to impede the cardiac tissues function. Until now, there was no single sensor capable of measuring the hearts dual properties without interfering with its functioning.

The new device is built of two critical components, explains lead author Hongyan Gao, who is pursuing his Ph.D. in electrical engineering at UMass Amherst. The first is a three-dimensional cardiac microtissue (CMT), grown in a lab from human stem cells under the guidance of co-author Yubing Sun, associate professor of mechanical and industrial engineering at UMass Amherst. CMT has become the preferred model for in vitro testing because it is the closest analog yet to a full-size, living human heart. However, because CMT is grown in a test tube, it has to mature, a process that takes time and can be easily disrupted by a clumsy sensor.

The second critical component involves graphenea pure-carbon substance only one atom thick. Graphene has a few surprising quirks to its nature that make it perfect for a cardiac sensor. Graphene is electrically conductive, and so it can sense the electrical charges shooting through cardiac tissue. It is also piezoresistive, which means that as it is stretchedsay, by the beating of a heartits electrical resistance increases. And because graphene is impossibly thin, it can register even the tiniest flutter of muscle contraction or relaxation and can do so without impeding the hearts function, all through the maturation process. Co-author Jing Kong, professor of electrical engineering at MIT, and her group supplied this critical graphene material.

Although there have already been many applications for graphene, it is wonderful to see that it can be used in this critical need, which takes advantage of graphenes different characteristics, says Kong.

Gao, Yao and their colleagues then embedded a series of graphene sensors in a soft, stretchable porous mesh scaffold they developed that has close structural and mechanical properties to human tissue and which can be applied non-invasively to cardiac tissue.

No one has ever done this before, says Gao. Graphene can survive in a biological environment without degrading for a very long time and not lose its conductivity, so we can monitor the CMT across its entire maturation process.

This is crucial for a number of reasons, adds Yao. Our sensor can give real-time feedback to scientists and drug researchers, and it can do so in a cost-effective way. We take pride in using the insights of electrical engineering to help build tools that can be useful to a wide range of researchers.

In the future, Gao says, he hopes to be able to adapt his sensor to grander scales, even to in vivo monitoring, which would provide the best-possible data to help solve cardiac disease.

This research was supported by the Army Research Office, the National Institutes of Health, the U.S. National Science Foundation, the Semiconductor Research Corporation, and the Link Foundation, as well as theInstitute for Applied Life Sciencesat UMass Amherst.

For more information:https://www.umass.edu/

Read the original here:
UMass Amherst Engineers Create Bioelectronic Mesh Capable of Growing with Cardiac Tissues for Comprehensive ... - Diagnostic and Interventional...

Recommendation and review posted by Bethany Smith

Microplastics dampen the self-renewal of hematopoietic stem cells by disrupting the gut microbiota-hypoxanthine-Wnt … – Nature.com

March 29th, 2024

Mice

C57BL/6J (CD45.2) and C57BL6.SJL (CD45.1) mice were purchased from The Jackson Laboratory and housed under specific pathogen-free conditions. Male and female mice from 8 to 12 weeks were used in experiments and provided with a suitable environment and sufficient water and food. After a week of acclimatization, each mouse was randomly divided into groups, given 100L pure water, 0.01mg/100L, or 0.1mg/100L MPs by oral gavage every two days for five weeks in a gavage experiment (n=5 for each group). For the intravenous injection experiment, MPs were administered into mouse blood via the tail vein at a rate of 0.1g/100L per week for a duration of 4 weeks (n=5 for each group). All animal experiments were first approved by the Laboratory Animal Welfare and Ethics Committee of Zhejiang University (AP CODE: ZJU20220108).

Indocyanine green polystyrene (ICG-PS), polystyrene (PS) and polymethyl methacrylate (PMMA) particles were obtained from Suzhou Mylife Advanced Material Technology Company (China). Polyethylene (PE) particles were purchased from Cospheric (USA). Scanning electron microscopy (SEM, Nova Nano 450, FEI) was used to characterize the primary sizes and shapes of different MPs20. MPs were dispersed in ultrapure water with sonication before dynamic light scattering analysis (Zetasizer, Malvern, UK) to determine the hydrodynamic sizes and zeta potentials49.

Mice were sacrificed and organs were removed within six hours of ICG-PS gavage, including the heart, lung, kidney, spleen, liver, gastrointestinal tissues and bone marrow. Feces were collected 1h before the mice were sacrificed. Both organs and feces were monitored by ex vivo bioluminescence imaging with a small-animal imaging system50 (IVIS Spectrum, PerkinElmer).

For flow cytometry analysis and isolation of hematopoietic stem and progenitor cells, cells were stained with relevant antibodies51 in PBS with 2% fetal bovine serum for 3045min on ice. Antibody clones that were used: Sca-1-PE-Cy7, c-Kit-APC, CD150-PE, CD48-BV421, CD45.1-FITC, CD45.2 PE-Cy5, Gr-1-PE-Cy5, Mac1-PE-Cy5, IgM-PE-Cy5, CD3-PE-Cy5, CD4- PE-Cy5, CD8-PE-Cy5, CD45R-PE-Cy5 and Ter-119-PE-Cy5. Detailed antibody information is summarized in Supplementary Table S6. HSPCs were stained with a lineage antibody cocktail (Gr-1, Mac1, CD3, CD4, CD8, CD45R, TER119 and B220), Sca-1, c-Kit, CD150 and CD48. Cell types were defined as followed: LSK compartment (LinSca-1+c-Kit+), LT-HSC (LSK CD150+CD48), ST-HSC (LSK CD150CD48), MPP2 (LSK CD150+CD48+) and MPP3/4 (LSK CD150CD48+). B cells (CD45.2+Mac1Gr-1+B220+), T cells (CD45.2+Mac1Gr-1+CD3+) and myeloid cells (CD45.2+Mac1+Gr-1). Samples were analyzed on a flow cytometer (CytoFLEX LX, Beckman). For sorting HSCs, lineage antibody cocktail-conjugated paramagnetic microbeads and MACS separation columns (Miltenyi Biotec) were used to enrich Lin cells before sorting. Stained cells were re-suspended in PBS with 2% FBS and sorted directly using the Beckman moflo Astrios EQ (Beckman). Flow cytometry data were analyzed by FlowJo (BD) software.

Apoptosis of cells was detected by Annexin V staining (Yeason, China). After being extracted from the bone marrow of mice, 5106 cells were labeled with different surface markers for 30 to 45min at 4C and then twice rinsed with PBS. Subsequently, the cells were reconstituted in binding buffer and supplemented with Annexin V. After 30min of incubation, flow cytometry was detected in the FITC channel. Cell cycle analysis was performed with the fluorescein Ki-67 set (BD Pharmingen, USA), following the directions provided by the manufacturer. Briefly, a total of 5106 bone marrow cells were labeled with corresponding antibodies, as previously stated. Afterward, the cells were pre-treated with a fixation/permeabilization concentrate (Invitrogen, USA) at 4C overnight and subsequently rinsed with the binding buffer. The cells were stained with Ki-67 antibody for 1h in the dark and then with DAPI (Invitrogen) for another 5min at room temperature. Flow cytometry data were collected by a flow cytometer (CytoFLEX LX, Beckman, USA).

HSCs were sorted by flow cytometry according to the experimental group (ctrl and PSH mice, Rikenellaceae treatment or hypoxanthine treatment). 150 HSCs were seeded in triplicate on methylcellulose media52 (M3434, Stemcell Technologies, Inc.). After 8 days, the number of colonies was counted by microscopy. In addition, 5000 BM cells were seeded and analyzed the same way as HSCs. The cell culture media was diluted in PBS and subjected to centrifugation at 400g for 5min to determine the total cell number.

Recipient mice (CD45.1) were administered drinking water with Baytril (250mg/L) for 7 days pre-transplant and 10 days post-transplant. The day before transplantation, recipients received a lethal dose of radiation (4.5Gy at a time, divided into two times with an interval of 4h). In primary transplantation, 2105 bone marrow cells from the ctrl or PS group (CD45.2) mice and 2105 recipient-type (CD45.1) bone marrow cells were transplanted into recipient mice (CD45.1) mice. Cells were injected into recipients via tail vein injection. Donor chimerism was tracked using peripheral blood cells every 4 weeks for at least 16 weeks after transplantation. For secondary transplantation, donor BM cells were collected from primary transplant recipients sacrificed at 16 weeks after transplantation and transplanted at a dosage of 2106 cells into irradiated secondary recipient mice (9Gy). Analysis of donor chimerism and the cycle of transplantation in secondary transplantation were the same as in primary transplantation.

For limiting dilution assays52, 1104, 5104 and 2105 donor-derived bone marrow cells were collected from ctrl or PS mice (CD45.2) and transplanted into irradiated (9Gy) CD45.1 recipient mice with 2105 recipient-type (CD45.1) bone-marrow cells. Limiting dilution analysis was performed using ELDA software53. 16 weeks after transplantation, recipient mice with more than 1% peripheral-blood multilineage chimerism were defined as positive engraftment. On the other hand, recipient mice undergoing transplantation that had died before 16 weeks post transplantation were likewise evaluated as having failed engraftment54.

For histological analysis, small intestines were collected and fixed in 4% paraformaldehyde and embedded in paraffin, sectioned (5m thickness), and stained with H&E at ZJU Animal Histopathology Core Facility (China). We used Chius scores33,34 to evaluate the damage for each sample. The grade was as follows: 0, normal mucosa; 1, development of subepithelial Gruenhagens space at the tip of villus; 2, extension of the Gruenhagens area with moderate epithelial lifting; 3, large epithelial bulge with a few denuded villi; 4, denuded villi with lamina propria and exposed capillaries; and 5, disintegration of the lamina propria, ulceration, and hemorrhage. For TEM analysis, slices of the small intestine were fixed with 2.5% glutaraldehyde for ultra-microstructure observation of intestinal epithelial cells. The samples were postfixed for one hour at 4C with 1% osmium tetroxide and 30min with 2% uranyl acetate, followed by dehydration with a graded series of alcohol solutions (50%, 70%, 90% and 100% for 15min each) and acetone (100% twice for 20min). Subsequently, they were embedded with epon (Sigma-Aldrich, MO, US) and polymerized. Ultrathin sections (6080nm) were made, and examined using TEM (Tecnai G2 Spirit 120kV, Thermo FEI).

In the short-term and long-term mouse models for MP ingestion, mice were fasted for 4h before oral gavage of FITC-dextran (4kD, Sigma). The fluorescence intensity of FITC-dextran (50mg/100g body weight) was measured in the peripheral blood after 2h of gavage. Fluorescence was measured using a microplate reader (Molecular Devices, SpectraMax iD5) with excitation at 490nm and emission at 520 nm29.

Fecal samples (about 3050mg per sample) were collected from the ctrl, PSL and PSH mice, quickly frozen in liquid nitrogen, and stored at 80C. DNA samples for the microbial community were extracted using E.Z.N.A. Stool DNA Kit (Omega, USA), according to the manufacturers instructions. In brief, polymerase chain reaction (PCR) amplification of prokaryotic 16S rDNA gene V3V4 region was performed using the forward primer 341F (5-CCTACGGGNGGCWGCAG-3) and the reverse primer 805R (5-GACTACHVGGGTATCTAATCC-3)55. After 35 cycles of PCR, sequencing adapters and barcodes were included to facilitate amplification. The PCR products were detected by 1.5% agarose gel electrophoresis and were further purified using AMPure XT beads (Beckman Coulter Genomics, Danvers, MA, USA), while the target fragments were recovered using the AxyPrep PCR Cleanup Kit (Axygen, USA). In addition, the amplicon library was quantified with the Library Quantification Kit for Illumina (Kapa Biosciences, Woburn, MA, USA), and sequenced on the Illumina NovaSeq PE250 platform. In bioinformatics pipeline29,56, the assignment of paired-end reads to samples was determined by their unique barcode, and subsequently shortened by cutting off the barcode and primer sequence. The paired-end reads were combined by FLASH (v1.2.8). Quality filtering on the raw reads was carried out under precise parameters to obtain high-quality clean tags according to fqtrim (v0.94). The chimeric sequences were filtered by Vsearch software (v2.3.4). After the dereplication process using DADA2, we acquired a feature table and feature sequence. The bacterial sequence fragments obtained were grouped into Operational Taxonomic Units (OTUs) and compared to the Greengenes microbial gene database using QIIME2. Alpha diversity and beta diversity were generated by QIIME2, and pictures were drawn by R (v3.2.0). The species annotation sequence alignment was performed by Blast, with the SILVA and NT-16S databases as the alignment references. Additional sequencing results are provided in Supplementary Table S1. The experiment was supported by Lc-Bio Technologies.

The methods for the analysis of feces from HSCT donors were slightly different from those used for mice. All samples were stored in the GUHE Flora Storage buffer (GUHE Laboratories, China). The bacterial genomic DNA was extracted with the GHFDE100 DNA isolation kit (GUHE Laboratories, China) and quantified using a NanoDrop ND-1000 spectrophotometer (Thermo Fisher Scientific, USA). The V4 region of the bacterial 16S rDNA genes was amplified by PCR, with the forward primer 515F (5-GTGCCAGCMGCCGCGGTAA-3) and the reverse primer 806R (5-GGACTACHVGGGTWTCTAAT-3). PCR amplicons were purified with Agencourt AMPure XP Beads (Beckman Coulter, IN) and quantified by the PicoGreen dsDNA Assay Kit (Invitrogen, USA). Following the previously reported steps57, the paired-end 2150bp sequencing was performed on the Illumina NovaSeq6000 platform. The details of bacterial OTUs are summarized in Supplementary Table S5. Sequence data analyses were performed using QIIME2 and R packages (v3.2.0).

For metabolite evaluation, samples from mice feces were prepared and detected as previously described55,58,59. In a nutshell, metabolites were extracted from feces through precooled 50% methanol buffer and stored at 80C before the LCMS analysis. All chromatographic separations were conducted using an ultra-performance liquid chromatography (UPLC) system (SCIEX, UK). A reversed phase separation was performed using an ACQUITY UPLC T3 column (100mm * 2.1mm, 1.8m, Waters, UK). The temperature of the column oven was maintained at 35C and the flow rate was 0.4mL/min. Both positive (the ionspray voltage floating set at 5000V) and negative ion modes (4500V) were analyzed using a TripleTOF 5600 Plus high-resolution tandem mass spectrometer (SCIEX, UK). The mass spectrometry data were obtained in Interactive Disassembler Professional (IDA) mode, with a time-of-flight (TOF) mass range of 60 to 1200Da. The survey scans were acquired in 150 milliseconds and product ion scans with a charge state of 1+ and 100 counts per second (counts/s) were recorded up to 12. Cycle duration was 0.56s. Stringent quality assurance (QA) and quality control (QC) procedures were applied, as the mass accuracy was calibrated every 20 samples and a QC sample was obtained every 10 samples. LCMS raw data files underwent processing in XCMS (Scripps, La Jolla, CA) to perform peak picking, peak alignment, gap filling, and sample normalization. Online KEGG was adopted to annotate metabolites through the matching between the precise molecular mass data (m/z) of samples and those from the database. PCA and volcano plot were utilized to identify ion characteristics that exhibit significant differences between the groups. The details of metabolomes can be found in Supplementary Table S2. The experiment was supported by Lc-Bio Technologies.

Before FMT, SPF mice received a 200L antibiotic treatment (1g/L ampicillin, 0.5g/L neomycin, 0.5g/L vancomycin and 1g/L metronidazole) for three consecutive days by oral gavage. Fresh feces were collected from ctrl or PS mice and resuspended in reduced PBS (0.5g/L cysteine and 0.2g/L Na2S in PBS) at a ratio of about 120mg feces/mL reduced PBS. Feces were then centrifuged at 500g for 1min to remove insolubilize particles25. Recipients (C57BL/6J mice) were administered 100mL of the supernatant from different groups by oral gavage twice every week for 4 weeks. 2 days after the last FMT, recipients were euthanized to analyze the changes in the hematopoietic system.

The Rikenellaceae strain (ATCC BAA-1961), purchased from ATCC, was cultured in an anaerobic chamber using BD Difco Dehydrated Culture Media: Reinforced Clostridial Medium at a temperature of 37C with a gas mixture of 80% N2 and 20% CO2. The final concentration of Rikenellaceae was 2108 viable c.f.u. per 100L and hypoxanthine (200mg/kg, Sigma, Germany) was dissolved in double distilled water29. Mice first received antibiotic treatment (same as FMT) and were then treated by oral gavage with 100L of either Rikenellaceae or hypoxanthine suspension three times a week for 4 weeks. Reinforced Clostridial Medium or double distilled water was used as a vehicle control, respectively. 2 days after the last administration, recipients were euthanized to analyze the changes in the hematopoietic system. To examine the impact of hypoxanthine on HSCs, we exposed bone marrow cells to direct co-culture with hypoxanthine at a concentration of 100pg/mL for a period of 3 days.

Mouse bone marrow cells were harvested by flushing the mices tibia and femur in phosphate buffered saline (PBS) with 2% fetal bovine serum (GIBCO). Harvested cells were grown into 96-well u-bottom plates containing freshly made HSC culture medium (StemSpanTM SFEM, Stemcell Tec.) with SCF (50ng/mL; PeproTech) and TPO (50ng/mL; PeproTech), at 37C with 5% CO2. For HSC culture, the medium was changed every 3 days by manually removing half of the conditioned medium and replacing it with fresh medium60. To assess the effects of WNT10A, IL-17, TNF and NF-kappa B on hematopoiesis, we cultured HSCs in a basic medium and supplemented them with related proteins (10ng/mL; Cosmo Bio, USA) or PBS as a control for two days, followed by flow cytometry analysis. Different concentrations of PS were added to the medium and tested using CCK-8 and FACS to detect the effect of MPs on cultured HSCs.

1104 HSCs were obtained in triplicate from mouse bone marrow cells from the ctrl or PSH group by flow cytometry sorting and RNA was extracted with RNAiso Plus (Takara, Japan) according to the manufacturers protocol. The concentration and integrity of RNA were examined by Qubit 2.0 and Agilent 2100 (Novogene, China), respectively. Oligo (dT)-coated magnetic beads (Novogene, China) were used to enrich eukaryotic mRNA. After cDNA synthesis and PCR amplification, the PCR product was purified using AMPure XP beads (Novogene, China) to obtain the final library. The Illumina high-throughput sequencing platform NovaSeq 6000 was used for sequencing. Analysis of gene expression was calculated by R or the DESeq2 package61. Detailed information regarding RNA-seq is listed in Supplementary Table S3.

For RNA expression analysis, total RNA from bone marrow cells was extracted using Trizol (Invitrogen, US) and resuspended in nuclease-free water. Reverse transcription was performed using the QuantiTect Reverse Transcription kit (Qiagen NV). qPCR was conducted using cDNA, primers and SYBR-green (Takara, Japan) in 20L using the ABI 7500 Q-PCR system62. Results were calculated using the RQ value (RQ=2Ct). Mouse Actin was chosen as the normalization control. Gene-specific primer sequences are shown in Supplementary Table S7.

Bone marrow and Rikenellaceae supernatant in different groups were obtained by centrifugation. Fecal supernatant was obtained from human samples. Hypoxanthine (LANSO, China) and WNT10A (EIAab, China) were measured by ELISA with respective kits according to the manufacturers protocols.

Human feces and peripheral blood samples were obtained from 14 subjects who provided grafts for HSCT patients. They were divided into graft success group and graft failure (GS)/poor graft function (GF/PGF) group, with 7 participants in each group. Research involving humans was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital, College of Medicine, Zhejiang University (IIT20230067B). All participants read and signed the informed consent. Detailed information on patients was listed in Supplementary Table S4.

The Agilent 8700 Laser Direct Infrared Imaging system was utilized for fast and automated analysis of MPs in feces received from donors. An excessive nitric acid concentration (68%) was added to the sample and heated to dissolve the protein. Large particles were first intercepted with a large aperture filter and then filtered by vacuum extraction. After rinsing with ultra-pure water and ethanol several times, the materials, including MPs, were dispersed in the ethanol solution. The LDIR test was carried out when the ethanol was completely volatilized63. The sample of MPs was positioned on the standard sample stage. The stage was then put into the sample stage, and the Agilent Clarity was initiated to advance the sample stage into the sample chamber. The software rapidly scanned the chosen test area using a constant wave number of 1800cm1, and accurately detected and pinpointed the particles within the selected area. The unoccupied area devoid of particles was automatically designated as the background. The background spectrum was gathered and readjusted, followed by the visualization of detected particles and the collection of the whole infrared spectrum. After obtaining the particle spectrum, the spectrum library was utilized to carry out qualitative analysis automatically, including the inclusion picture, size, and area of each particle. The test was supported by Shanghai WEIPU Testing Technology Group.

MPs in peripheral blood from donors were tested by Py-GC/MS. Nitric acid was added to samples for digestion at 110C for 12h, and then used deionized water to make the solution weakly acidic. After concentration, the solution was dribbled into the sampling crucible of Py-GCMS and tested when the solvent in the crucible was completely volatilized17. Various standards of MPs were prepared and analyzed using Py-GCMS in order to construct the quantitative curve. PY-3030D Frontier was employed for lysis, with a lysis temperature set at 550 C. The chromatographic column dimensions were 30m in length, 0.25mm inner diameter, and 0.25m film thickness. The sample was subjected to a heat preservation period of 2min at 40C, followed by a gradual increase in temperature at a rate of around 20C per minute until it reached 320C. The sample was maintained at this temperature for 14min and the entire process takes a total of 30min. The carrier gas utilized was helium, with the ion source temperature of 230C. The split ratio employed was 5:1, and the m/z scan range spanned from 40 to 60064. The experiment was supported by Shanghai WEIPU Testing Technology Group.

Each animal experiment was tested using at least 56 replicates and each in vitro experiment was at least three replicates. Specific replication details are provided in relevant figure captions. Statistical significance was ascertained through unpaired two-tailed t-tests by GraphPad Prism when the P value was less than 0.05. Error bars in all figures indicate the standard deviation (SD).

Link:
Microplastics dampen the self-renewal of hematopoietic stem cells by disrupting the gut microbiota-hypoxanthine-Wnt ... - Nature.com

Recommendation and review posted by Bethany Smith

Hereditary Alzheimer’s Transmitted Via Bone Marrow Transplants – Neuroscience News

March 29th, 2024

Summary: Alzheimers disease, traditionally seen as a brain-centric condition, may have systemic origins and can be accelerated through bone marrow transplants from donors with familial Alzheimers to healthy mice.

A new study underscores the diseases potential transmission via cellular therapies and suggests screening donors for Alzheimers markers to prevent inadvertent disease transfer.

By demonstrating that amyloid proteins from peripheral sources can induce Alzheimers in the central nervous system, this research shifts the understanding of Alzheimers towards a more systemic perspective, highlighting the need for cautious screening in transplants and blood transfusions.

Key Facts:

Source: Cell Press

Familial Alzheimers disease can be transferred via bone marrow transplant, researchers show March 28 in the journalStem Cell Reports. When the team transplanted bone marrow stem cells from mice carrying a hereditary version of Alzheimers disease into normal lab mice, the recipients developed Alzheimers diseaseand at an accelerated rate.

The study highlights the role of amyloid that originates outside of the brain in the development of Alzheimers disease, which changes the paradigm of Alzheimers from being a disease that is exclusively produced in the brain to a more systemic disease.

Based on their findings, the researchers say that donors of blood, tissue, organ, and stem cells should be screened for Alzheimers disease to prevent its inadvertent transfer during blood product transfusions and cellular therapies.

This supports the idea that Alzheimers is a systemic disease where amyloids that are expressed outside of the brain contribute to central nervous system pathology, says senior author and immunologist Wilfred Jefferies, of the University of British Columbia.

As we continue to explore this mechanism, Alzheimers disease may be the tip of the iceberg and we need to have far better controls and screening of the donors used in blood, organ and tissue transplants as well as in the transfers of human derived stem cells or blood products.

To test whether a peripheral source of amyloid could contribute to the development of Alzheimers in the brain, the researchers transplanted bone marrow containing stem cells from mice carrying a familial version of the diseasea variant of the human amyloid precursor protein (APP) gene, which, when cleaved, misfolded and aggregated, forms the amyloid plaques that are a hallmark of Alzheimers disease.

They performed transplants into two different strains of recipient mice: APP-knockout mice that lacked an APP gene altogether, and mice that carried a normal APP gene.

In this model of heritable Alzheimers disease, mice usually begin developing plaques at 9 to 10 months of age, and behavioral signs of cognitive decline begin to appear at 11 to 12 months of age. Surprisingly, the transplant recipients began showing symptoms of cognitive decline much earlierat 6 months post-transplant for the APP-knockout mice and at 9 months for the normal mice.

The fact that we could see significant behavioral differences and cognitive decline in the APP-knockouts at 6 months was surprising but also intriguing because it just showed the appearance of the disease that was being accelerated after being transferred, says first author Chaahat Singh of the University of British Columbia.

In mice, signs of cognitive decline present as an absence of normal fear and a loss of short and long-term memory. Both groups of recipient mice also showed clear molecular and cellular hallmarks of Alzheimers disease, including leaky blood-brain barriers and buildup of amyloid in the brain.

Observing the transfer of disease in APP-knockout mice that lacked an APP gene altogether, the team concluded that the mutated gene in the donor cells can cause the disease and observing that recipient animals that carried a normal APP gene are susceptible to the disease suggests that the disease can be transferred to health individuals.

Because the transplanted stem cells were hematopoietic cells, meaning that they could develop into blood and immune cells but not neurons, the researchers demonstration of amyloid in the brains of APP knockout mice shows definitively that Alzheimers disease can result from amyloid that is produced outside of the central nervous system.

Finally the source of the disease in mice is a human APP gene demonstrating the mutated human gene can transfer the disease in a different species.

In future studies, the researchers plan to test whether transplanting tissues from normal mice to mice with familial Alzheimers could mitigate the disease and to test whether the disease is also transferable via other types of transplants or transfusions and to expand the investigation of the transfer of disease between species.

In this study, we examined bone marrow and stem cells transplantation. However, next it will be important to examine if inadvertent transmission of disease takes place during the application of other forms of cellular therapies, as well as to directly examine the transfer of disease from contaminated sources, independent from cellular mechanisms, says Jefferies.

Funding:

This research was supported by the Canadian Institutes of Health Research, the W. Garfield Weston Foundation/Weston Brain Institute, the Centre for Blood Research, the University of British Columbia, the Austrian Academy of Science, and the Sullivan Urology Foundation at Vancouver General Hospital.

Author: Kristopher Benke Source: Cell Reports Contact: Kristopher Benke Cell Reports Image: The image is credited to Neuroscience News

Original Research: The findings will appear in Stem Cell Reports

More here:
Hereditary Alzheimer's Transmitted Via Bone Marrow Transplants - Neuroscience News

Recommendation and review posted by Bethany Smith