About 1 out of 5 inherited cases of ALS occur due to mutations in SOD1. How these genetic changes contribute to ALS remains unclear. But according to a growing number of studies, these mutations result in the misfolding and aggregation of this metabolic enzyme, contributing to motor neuron toxicity by multiple mechanisms (see Taylor et al., 2016).

Silence, please. Scientists are developing gene therapy strategies for SOD1 ALS that aim to reduce levels of mutant SOD1 in key tissues affected by the disease including the brain and spinal cord. [Image: Rice University under a CC BY 4.0 license.]

A growing number of researchers are developing potential treatment strategies that aim to reduce levels of mutant SOD1 in the CNS in hopes to slow or stop the progression of the disease. One approach, which involves gene therapy, suppresses expression of the SOD1 gene through RNA silencing-based mechanisms. This strategy, according to a 2016 study led by University of Massachusetts Medical Schools Christian Mueller, can extend the lifespan of pre-onset adult SOD1 mice by up to 20% upon intrathecal injection (Borel et al., 2016).

Now, Martine Barkats and Maria Grazia Biferi of the Institute of Myology in Paris, France introduce a new gene therapy approach that increases survival of pre-symptomatic adult SOD1 G93A mice by more than 50%. An independent analysis, led by ALS Therapy Development Institutes Fernando Vieira and commissioned by Prize4Life, confirmed the teams results.

The Institute of Myology team received the Prize4Life $1.0 million USD Avi Kremer ALS Treatment Prize in recognition of reaching this key milestone. This is the best efficacy [observed] in a SOD1 mouse, said Nicole Szlezk, Chairman of Prize4Lifes Board of Directors in the US.

Maria Grazia Biferi unveiled the potential treatment strategy on April 25, 2017 at the ALS Association Drug Company Working Group, held during the 69th Annual Meeting of the American Academy of Neurology.

The approach builds on a previous strategy developed by Barkats team, using a related gene therapy delivery vehicle, for spinal muscular atrophy. A similar strategy, known as ChariSMA (AVXS-101), is now at the phase 1 stage and according to interim phase I results appears promising (see December 2015 news).

This is no longer an academic exercise, said Lucie Bruijn, Chief Scientist of the ALS Association. The current clinical trials in SMA confirm that this approach can succeed.

Going viral

In 2007, Martine Barkats team discovered that the recombinant adeno-associated virus AAV9 could penetrate the blood-brain barrier, opening the door to the development of gene therapies for motor neuron diseases. (see December 2008 news; Duque et al., 2009; Foust et al., 2009).

Every dog has its day. Researchers at Tufts University School of Medicine are now evaluating a potential gene therapy for SOD1-linked ALS in dogs. The approach aims to help dogs with a naturally occurring form of the disease known as canine degenerative myelopathy (DM), a late-onset disease first recognized in the 1970s in German Shepards. The trial is a key step toward developing a treatment for ALS, because dogs are larger and the disease is naturally occurring. [Image: Handicapped Pets. CC BY-SA 2.0 license.]

Building on these advances, research teams led by Nationwide Childrens Hospital Brian Kaspar in Ohio and University of Massachusetts Medical Centers Robert Brown began to develop potential therapies for SOD1 ALS. One of these strategies, being developed by Robert Brown and Christian Mueller at the University of Massachusetts Medical School, uses an artificial microRNA to reduce levels of mutant SOD1 synthesis in the brain and spinal cord. The approach is currently being evaluated at the preclinical stage in dogs with degenerative myelopathy (DM), a naturally occurring form of the disease. The clinical trial, being led by Tufts University School of Medicines Dominik Faissler in Massachusetts, launched in December 2016 and is ongoing.

The strategy builds in part, on previous studies led by Martine Barkats which found that AAV10 is more efficient than AAV9 in delivering genes into motor neurons in the spinal cord at lower doses, critical in developing a treatment for a disease (Tanguy et al., 2015). The approach, according to studies led by University of Californias Krystof S. Bankiewicz in San Francisco and University of Massachusetts Medical Centers Christian Mueller can be delivered efficiently intrathecally into motor neurons, at least in non-human primates.

Meanwhile, California Institute of Technologys Ben Deverman and Viviana Gradinaru used Cre-recombination-based AAV targeted evolution (CREATE), to develop novel gene therapy delivery vehicles that penetrate the blood brain barrier, to treat disorders of the central nervous system, including ALS. The vectors, which include AAV-PHP.B, can deliver genes into the motor cortex in the brain and the spinal cord at about 40 times greater efficiency compared to AAV9 upon intravenous injection (Deverman et al., 2016).

The delivery approach is now licensed to Cambridge startup Voyager Therapeutics in Massachusetts, which is also developing a gene therapy for SOD1 ALS. Voyager Therapeutics hopes to file an IND for their potential treatment strategy for ALS, known as VY-SOD101, at the end of 2017.

A key question is whether SOD1 is needed to reduce free radical levels that arise in key tissues affected by the disease. Therefore, a growing number of research teams are developing erase and replace strategies which aim to reduce mutant SOD1 while at the same time, produce the wild-type enzyme to help detoxify key tissues affected by ALS, including the brain, spinal cord and muscles.

A one, two punch?

Engineering a new approach. Researchers at University of Massachusetts Medical School are developing a CRISPR-Cas9-based gene therapy for SOD1-linked ALS that aims to permanently suppress mutant SOD1 synthesis. Meanwhile, Duke Universitys Charles Gersbach is developing a epigenomic editing-based strategy, also presented at AAN 2017, that may be of benefit to a wide range of diseases including the most common forms of ALS, C9orf72-linked disease (see January 2017 conference news; Thakore et al., 2015). [Courtesy of Ran et al., 2013, Nature Publishing Group.]

With the advent of new gene silencing technologies, research teams began to take another look at their gene therapy approaches and began to modify them in hopes to optimize their strategies to combat SOD1-linked disease. Robert Brown turned to CRISPR/Cas9 technologies in hopes to stop further mutant SOD1 synthesis. Their approach, unveiled at AAN 2017, uses imprecise CAS9-based editing to introduce indels in the SOD1 gene. The key obstacle, according to preliminary results presented by University of Massachusetts Medical Schools Zachary Taylor, is delivering sufficient Cas9 to modify the mutant SOD1 gene within motor neurons and glia in the central nervous system. Preclinical studies remain ongoing.

Across the globe, Martine Barkats and Maria Grazia Biferi, are developing a strategy using a novel gene silencing AAV10-based approach to tackle SOD1 ALS. The strategy is now being optimized and is at the preclinical stage. The approach involves the injection of the potential therapy into the blood and the brain. The reason, according to Biferi is to ensure that levels of the misfolded enzyme are reduced in key tissues outside the CNS including skeletal muscle.

This is important, explains Biferi, because ALS is beginning to be considered a multisystemic disease.

Now, the researchers are developing a similar strategy to tackle C9orf72 ALS, the most common form of the disease identified to date.

TARgeting ALS

A detox program for the CNS? Researchers at MeiraGTx in New York, in collaboration with Ronald Klein and Gregory Petsko, are developing a gene therapy strategy that aims to reduce the toxicity of TDP-43 by turning up nonsense-mediated mRNA decay. [Image: Emw, Wikimedia Commons.]

Meanwhile, Louisiana State Universitys Ronald Klein is setting his sights on helping to develop a gene therapy that targets more than 95% of cases of the disease. The approach, based on previous studies led by Gregory Petsko in New York, now at Weill Cornell Medical College in New York and Sami Barmada, now at the University of Michigan, aims to reduce cytoplasmic TDP43-mediated motor neuron toxicity by turning up nonsense-mediated mRNA decay. The gene therapy-based strategy increases levels of hUPF1, a key regulator of this process (see June 2015 news; Ju et al., 2011; Barmada et al., 2015).

The approach, according to a study from Kleins team, prolongs motor function at least for 8 weeks in a rat model of the disease. The study found that the potential therapy, when administered at day 1, preserved strength in the forelimbs of a rat model of ALS (see June 2015 news; Jackson et al., 2015).

It is really amazing that [increasing] hUPF has this really specific protective action against TDP-43, says Klein. We keep seeing it again and again.

How this strategy may mitigate TDP-43-mediated motor neuron toxicity remains unclear. The approach is one of at least two that aims to target TDP-43 buildup in the cytoplasm of motor neurons (see April 2017 news; Becker et al., 2017).

The strategy, now licensed to the New York biotech startup MeiraGTx, is at the preclinical stage. Evaluation of the approach in adult rat models of ALS is ongoing.

References

Borel F, Gernoux G, Cardozo B, Metterville JP, Toro Cabreja GC, Song L, Su Q, Gao GP, Elmallah MK, Brown RH Jr, Mueller C. Therapeutic rAAVrh10 Mediated SOD1 Silencing in Adult SOD1(G93A) Mice and Nonhuman Primates. Hum Gene Ther. 2016 Jan;27(1):19-31. doi: 10.1089/hum.2015.122. [PubMed].

Duque S, Joussemet B, Riviere C, Marais T, Dubreil L, Douar AM, Fyfe J, Moullier P, Colle MA, Barkats M. Intravenous administration of self-complementary AAV9 enables transgene delivery to adult motor neurons. Mol Ther. 2009 Jul;17(7):1187-96. [PubMed].

Foust KD, Nurre E, Montgomery CL, Hernandez A, Chan CM, Kaspar BK. Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol. 2009 Jan;27(1):59-65 [PubMed].

Tanguy Y, Biferi MG, Besse A, Astord S, Cohen-Tannoudji M, Marais T, Barkats M. Systemic AAVrh10 provides higher transgene expression than AAV9 in the brain and the spinal cord of neonatal mice. Front Mol Neurosci. 2015 Jul 28;8:36. doi: 10.3389/fnmol.2015.00036. eCollection 2015. [PubMed].

Barmada SJ, Ju S, Arjun A, Batarse A, Archbold HC, Peisach D, Li X, Zhang Y, Tank EM, Qiu H, Huang EJ, Ringe D, Petsko GA, Finkbeiner S. Amelioration of toxicity in neuronal models of amyotrophic lateral sclerosis by hUPF1. Proc Natl Acad Sci U S A. 2015 Jun 23;112(25):7821-6. [PubMed].

Jackson KL, Dayton RD, Orchard EA, Ju S, Ringe D, Petsko GA, Maquat LE, Klein RL. Preservation of forelimb function by UPF1 gene therapy in a rat model of TDP-43-induced motor paralysis. Gene Ther. 2015 Jan;22(1):20-8. [PubMed].

Ju S, Tardiff DF, Han H, Divya K, Zhong Q, Maquat LE, Bosco DA, Hayward LJ, Brown RH Jr, Lindquist S, Ringe D, Petsko GA. A yeast model of FUS/TLS-dependent cytotoxicity. PLoS Biol. 2011 Apr;9(4):e1001052. [PubMed].

Becker LA, Huang B, Bieri G, Ma R, Knowles DA, Jafar-Nejad P, Messing J, Kim HJ, Soriano A, Auburger G, Pulst SM, Taylor JP, Rigo F, Gitler AD. Therapeutic reduction of ataxin-2 extends lifespan and reduces pathology in TDP-43 mice. Nature. 2017 Apr 20;544(7650):367-371. [PubMed].

Further Reading

van Zundert B, Brown RH Jr. Silencing strategies for therapy of SOD1-mediated ALS. Neurosci Lett. 2017 Jan 1;636:32-39. [PubMed].

Tora MS, Keifer OP Jr, Lamanna JJ, Boulis NM. The challenges of developing a gene therapy for amyotrophic lateral sclerosis. Expert Rev Neurother. 2017 Apr;17(4):323-325. [PubMed].

AAN2017 c9orf72 disease-als gene therapy SOD1 tdp-43 topic-preclinical topic-randd

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A New Potential ALS Gene Therapy Delivers A Key Milestone - ALS Research Forum

Recommendation and review posted by Bethany Smith

In Brief Researchers from Johns Hopkins Medicine in Maryland have discovered a rather unusual way to treat a severe form of age-related blindness. They found a virus inserted into the retina can be used to halt or even reverse the disease. A Unique Treatment

They say you dont fight fire with fire. However, researchers from Johns Hopkins Medicine in Maryland have found that sometimes a virus may be the best weapon against a disease.Their studyhas been publishedin The Lancet

The researchers werelooking for ways to treat a particular type ofage-related macular degeneration (AMD)known as a wet AMD. Its a rare and more severe form of the disease,affecting just 10 percent of all AMD patients, and it causes new blood vessels to grow under the retina, which then leak blood and fluid into the eye, leading to vision problems.

The researchers knewthey could halt and even reverse the condition by suppressing an overactive protein called vascular endothelial growth factor (VEGF). Other researchers had been able to do it with monthly eye injections, but this team was hoping to do it with just one injection.

The best way they found to do this was by using a common cold-like virus called AAV2 as a carrier of gene that activates the production of a differentprotein,sFLT01, tocounter VEGF.

In a preliminary trial involving 19 men and women 50 years old and above, the researchers injected the patients with a form of AAV2that was genetically engineered to penetrate retinal cells and deposit the gene. After the virus deposited the gene, the cells began secreting sFLT01 which bound to VEGF and prevented it from stimulating leakage and growth of abnormal blood vessels, explained a Johns Hopkins press release.

The clinical trial showed promising results, with the condition of four of the patients improving dramatically after just one viral injection. Two others saw some reduction in the fluid build up, and the treatment didnt produce any side effects in any patients. Even at the highest dose, the treatment was quite safe. We found there were almost no adverse reactions in our patients, said researcher Peter Campochiaro.

Of the patients that didnt respond, the researchers discovered that five naturally produced antibodies that would attack the AAV2 virus, rendering it unable to complete its gene depositing mission. They think these antibodies could be prevalent throughout the population, making it difficult to determine how effecting the treatment would actually be.

Nevertheless, this research is a step in the right direction, especially with AMD expected to affect almost 5.44 million people in the U.S. by 2050. This preliminary study is a small but promising step towards a new approach that will not only reduce doctor visits and the anxiety and discomfort associated with repeated injections in the eye, but may improve long-term outcomes, Campochiaro said.

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An Experimental Gene Therapy Uses Viruses to Stop Age-Related ... - Futurism

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19 May 2017 Gene therapy might someday help mend badly broken bones This experimental method combines gene therapy, stem cells and ultrasound

Researchers have found that an experimental technique has healed large bone breaks in lab animals, researchers have found.

The technique is still far from becoming a reality, but, it repaired large bone gaps in the mini-pigs scientists studied. The hope, the researchers say, is to eventually help people with badly broken bones that won't heal.

The results of the study were published in Science Translational Medicine.

When a bone sustains a simple fracture, it is usually able to self-repair with time (and a cast). However, severe fractures can leave large gaps in the bone that the self-healing process cannot bridge.

The aim of gene therapy

Health24 previously reported that the basic function of genes is to regulate the production of proteins required for the healthy working of cells. Thus, genetic defects manifest in either too little or too much of a protein being produced.

The aim of gene therapy is to replace the defective gene with a healthy one. The correct amount of proteins will be produced, and the disease will then be cured.

Geneticists are literally snipping defective pieces out of a strand of DNA with molecular scissors called CRISPR.

Bone grafting

Right now, the "gold standard" treatment for those fractures is bone grafting, said Dan Gazit, one of the senior researchers on the new study.

There, surgeons take bone tissue from elsewhere in the body or from a donor and use it to repair the damaged bone.

When bone grafting is done with a patient's own tissue often taken from the pelvis that means additional surgery. And it can leave patients with prolonged pain and added risk of infection, Gazit said.

Newapproach

First, the researchers implanted a matrix of collagen a protein in bone into the gap between the two sides of a fractured bone.

That collagen then attracted the bone's resident stem cells, and gave them a structure to settle into. Stem cells are early cells that develop into mature tissue, including bone.

Once those cells have populated the gap in the bone, the next step involves gene therapy. The researchers injected a mixture of "microbubbles" and genetic material for a bone-promoting protein, called BMP, into the injury site.

That spurred the stem cells to form new bone tissue, according to the report.

In this study, the tactic healed bone breaks in all of the lab animals the researchers treated, Gazit said. In untreated pigs, the breaks did not heal, the findings showed.

A sophisticated approach needed

"But there are problems with BMP," said Dr Joseph Lane, an orthopaedic trauma surgeon at the Hospital for Special Surgery in New York City.

A central issue, he said, is that very high BMP doses may be needed, and side effects including infections and excess bone growth are common.

The new approach is "going in that direction", said Lane, who was not involved in the research. The "beauty" of it, he said, is that it harnesses the bone-promoting effects of BMP in a more natural way.

A number of questions should be answered before human trials are done, according to Lane. For example, he said, future animal research should look at more complicated fractures. The bone injuries used in this study are relatively easy to heal, versus severe fractures, Lane said.

Read more:

6 lifestyle triggers for broken bones

Menopause before 40 carries higher risk of broken bones

Patients in Mpumalanga are going home with broken bones

People with recessive dystrophic epidermolysis bullosa aren't able to produce a protein that binds the upper and lower levels of skin together, and at the slightest friction, these layers slide and create blisters.

Tereza is the CEO of the National Osteoporosis Foundation and worked as a Nursing Sister in the field of Osteoporosis for 18 years prior to her appointment with the Foundation. She used to be the Educational Officer for the Foundation and co-wrote the patient brochure on Osteoporosis. Read more

The information provided does not constitute a diagnosis of your condition. You should consult a medical practitioner or other appropriate health care professional for a physical exmanication, diagnosis and formal advice. Health24 and the expert accept no responsibility or liability for any damage or personal harm you may suffer resulting from making use of this content.

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New gene therapy for vision loss is safe in humans, study suggests Science Daily In a small and preliminary clinical trial, Johns Hopkins researchers and their collaborators have shown that an experimental gene therapy that uses viruses to introduce a therapeutic gene into the eye is safe and that it may be effective in preserving ... and more »

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New gene therapy for vision loss is safe in humans, study suggests - Science Daily

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A test commonly used in breast cancer has been found to also identify which patients with aggressive prostate cancer will benefit from hormonal therapy, according to a study led by scientists at UC San Francisco and the University of Michigan.

While hormone therapy has been used successfully to treat many prostate cancer patients, until now, researchers have been unable to predict which patients would benefit from early initiation of this therapy following surgery. The study, conducted by a team of researchers at 11 medical centers nationwide and in Canada, demonstrates the first new way to select the best treatment for specific patients.

In the study, which appears today in the journalJAMA Oncology, the researchers divided prostate tumors into three subtypes based on genetic patterns. Their results reveal that starting hormone treatment after surgery prevents the spread of the tumor in only one of the three types, known as luminal B, a particularly aggressive form that affects about one-third of those with the disease.

Hormone therapy carries significant side effects, so knowing which patients are likely to benefit from it can focus treatment on the right patients at the appropriate time, while sparing the others of increased risk of fatigue, sexual dysfunction, osteoporosis, diabetes and other conditions.

If confirmed, patients with the luminal B subtype could be selected for early initiation of hormone therapy, which would allow for treatment intensification for patients most likely to benefit from it, saidFelix Feng, a radiation oncologist with UCSF Health and a senior author of the study.

Weve clearly shown that there are different molecular subtypes of prostate cancer and that a test widely used in breast cancer can also potentially be used to help individualize therapy for prostate cancer patients as well. said Feng,a UCSF associate professor of Radiation Oncology, Urology, and Medicine, who specializes in the treatment of high-risk, aggressive prostate cancers. He is also a member of the UCSF Helen Diller Family Comprehensive Cancer Center.

The hormone treatment is known as androgen-deprivation therapy, or ADT. Just as estrogen has been found to promote breast cancer growth, male sex hormones called androgens notably testosterone stimulate prostate cancer. As in breast cancer treatment, depriving cancer of the critical sex hormone can starve some prostate tumors.

The test, called PAM50, has been used for over a decade to identify which breast cancers are the best candidates for hormone treatment. But no such screen has been available for prostate cancer, Feng said. The new research shows that PAM50 can also distinguish between the three prostate cancer subtypes.

Ultimately, our goal is to find the right treatment for the right patient at the right time, said Feng. Using the PAM50 test may allow us to take the first step towards this goal, in the setting of hormone therapy for prostate cancer patients treated with surgery.

Fengs co-senior author on the research paper, Daniel Spratt, a radiation oncologist at the University of Michigan, commented on the potential of the biomarker to distinguish between the three prostate cancer subtypes: luminal B, luminal A and basal.

Prostate cancer has seen a recent surge of both investigational and commercially available prognostic biomarkers, Spratt said. Luminal and basal subtyping can be added to a very short list of predictive biomarkers in prostate cancer to truly personalize treatment for prostate cancer patients.

The retrospective study focused on 1,567 prostate cancer samples from high-risk patients who had undergone radical prostatectomy. The scientists identified the three distinct gene expression profiles that define the three cancer subtypes and confirmed the finding in another 6,300 prostate cancer samples.

They determined that luminal B disease was the most aggressive, with metastases recurring in about half of the patients over 10 years, compared to about one quarter of the patients with the luminal A or basal subtype.

They found that ADT treatments were more effective with luminal B tumors and may even have worsened prognosis in the other types of tumors a finding that would need to be confirmed with a prospective study and to firmly establish the biomarker finding as a diagnostic tool to guide treatment, said Feng.

Feng and Spratt will co-lead a large, National Cancer Institute-funded prospective clinical trial involving as many as a hundred clinical research sites, using the PAM50 assay to identify patients by their cancer subtype, and then randomly assign them to treatment with radiation and a placebo or radiation and hormone therapy treatment.

Our research published today, while very provocative, needs to be validated in this prospective study, the researchers said. Were hopeful that the biomarkers will prove to be a robust predictor of hormone treatment success, so we can increase survival of even the most aggressive cases and at the same time limit hormone treatment to those patients most likely to benefit from it.

In addition to Feng and Spratt, co-authors include first author Shuang G. Zhao, from the Department of Radiation Oncology, University of Michigan, as well as additional researchers from UCSF; the University of Michigan, Ann Arbor, Mich.; GenomeDx Biosciences, Inc., Vancouver, British Columbia; the University of Wisconsin, Madison; Thomas Jefferson University, Philadelphia, Penn.; Cedars-Sinai Medical Center, Los Angeles, Cal.; Cleveland Clinic, Cleveland, Ohio; University of British Columbia, Vancouver, BC; Mayo Clinic, Rochester, Minn.; Johns Hopkins Medical Institutions, Baltimore, Md.; Northwestern University, Chicago, Ill.; and Harvard Medical School, Cambridge, Mass. The full list of authors, institutional citations, and declared conflicts of interest can be found in the full paper.

Funding for the study was provided by the Prostate Cancer Foundation, Evans Foundation, V Foundation for Cancer Research, and A. Alfred Taubman Medical Research Institute.

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Doctors have been adding a new tool to the arsenal of how they restore the sex lives ofmenopausaland post-menopausal women: the humble vibrator.

With the onset of menopause, a decrease in the production of hormones causes vaginal tissue to get thinner and drier. Vaginal muscles can also atrophy, leading to painfulsex a problem for half of all menopausal and post-menopausal women, according to the National Institutes of Health.But the solution might be as simple as a vibrating piece of silicon.

Vibrators that are used internally stimulate pelvic blood flow, which increases vaginal moisture and boosts sexual response, all of which makes sex (with or without a partner) better. Like any muscle, the vagina is best kept healthy with regular exercise its the use it or lose it thing. Deterioration of this muscle becomes more common as middle-age or older women find themselves in situations where they arent sexually active anymore single, divorced, widowed or just not having regular sex with partners.

Therapeutically speaking, frequent vibrator use can prevent and ward off conditions such as painful vaginal dryness and atrophy. And yes, doctors are recommending their use with the caveat that since the vibrator industry isnt regulated, certain cautionary steps should be taken. (In brief:Keep anything you put inside your privates clean, and dont share your toys with friends.)

Dr. Barb DePree, whos been a gynecologist for about 30 years and was recognized by the North American Menopause Society in 2013 as the practitioner of the year for her exceptional contributions to menopause care, has long been prescribing vibrators to her patients. She keeps one handy in the exam room when she explains to her menopausal patients why regular vibrator use will be beneficial to their health, and suggests they try it.

While a few patients might have blushed through the years, all of them have been willing to take it for a spin, DePress told HuffPost. She explains that vibrators that stimulate just the clitoris might be fun, but for intercourse with a partner to resume pain-free, there must be pelvic floor activity.

One of her patients is a 70-year-old woman who reports having sex two or three times a week now without the use of lubricants or estrogen creams. She doesnt always achieve an orgasm, but according to her doctor, is quite pleased with what working with a vibrator for a few months accomplished.

DePree draws this analogy: When your vision started to fail, you didnt give up reading. You went out and bought yourself a pair of readers. Same thing is true about sex.

A survey of more than 2,000 women aged 18 to 60 indicated that 52 percent have used a vibrator.

Another benefit of vibrator use, said DePree, is they can help address the fact that orgasm intensity weakens with age. She said she commonly hears women say, Orgasm takes so much longer, and comes and goes so quickly its hardly worth it. She said, Those are the women who may benefit from introducing a vibrator too.

In a published paper she authored, DePree discussed a 52-year-old post-menopausal patient who sought her help. The woman estimated that at least five years had passed since she last experienced an orgasm. The patient had multiple sclerosis and was taking a selective serotonin reuptake inhibitor. She had tried a vibrator in the past, without success.

As a physician, I knew that she needed a more powerful motor for more intense stimulation. I was able to let her feel the difference and obtain the appropriate vibrator. Imagine her appreciation when she returned after achieving success, DePree said.

Having vibrators to road test in the safety of a doctors office also seems to be a boon. Not every woman feels comfortable going into a sex toy shop for the purchase. Online, the choices are mind-boggling. There are hundreds to choose form, and they can range in price from under $10 to the super-deluxe MotorBunny for $900 and the even higher priced Sybian.

Dr. Mary Jane Minkin, a Yale University obstetrician and gynecologist, brought vibrators out from under the bed a few years ago when she began prescribing them to Yale Cancer Clinics cancer patients, who often struggle with early menopause and need to combat its side effects. The vibrators increased her patients blood flow, and yes, improved their sex lives.

While the American Congress of Obstetricians and Gynecologists, the primary professional organization for ob-gyns, doesnt have an official policy on using vibrators to treat menopause and post-menopausal symptoms, a spokeswoman from the group told HuffPost that the organization doesnt really take issue with it.

And the organization does recommend masturbation to combat painful sex. I believe you could extrapolate that external stimulus, like a vibrator, fits into those categories, said Maggie McEvoy of the ACOG communications staff.

There are, of course, other options to help restore the vaginas elasticity and health for those who are unable or unwilling to go the vibrator route.

Hormone replacement therapy is controversial, but still on the table. Its use to treat symptoms of menopause changed abruptly after a large clinical trial in the U.K.found that the treatment actually posed more health risks, like breast cancer,than benefits for one type of hormone therapy.

But further review of clinical trials and new evidence show that hormone therapy may be a good choice for certain women, depending on their risk factors.Low-dose vaginal preparations of estrogen which come in cream, tablet or ring form can effectively treat vaginal symptoms and some urinary symptoms, while minimizing absorption into the body, says the Mayo Clinic.

There are also vaginal lasers, a relatively new FDA-approved treatment, that work by stimulating collagen production along vaginal walls, helping to build up the tissue again. The MonaLisa Touch and similar laser processes require three treatments (spaced a month apart) and cost about $3,000 that likely wont be covered by your insurance.

On the plus side, there have been18 studies that speak to the MonaLisa Touchs efficacy, all largely positive. One Stanford university study of 30 women found that all of them responded positively to the treatment. They showed highly statistically significant improvement in symptoms including dryness, pain, itching, painful urination and painful intercourse after the first treatment.

The North American Menopause Society gives the process a resounding maybe. It notes that the FDA approval process for devices is less strenuous than the one for new drugs, and these products havent survived the test of time yet. Meaning: They havent been around long enough to know the longer-term results.

The procedure itself doesnt hurt, but does require an annual maintenance treatment.You also shouldnt have laser therapy until youve had a Pap test and a thorough exam by your doctor to ensure that there are no other medical issues such as fibroids causing the pain.

Options are a good thing, right?

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When Your Doctor Prescribes A Vibrator - HuffPost

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Agnes LLOYD-PLATT

This isnt what I came for. Id walked into the acupuncture clinic close to my house - one of those mysterious places that lists ailments in the window to draw people in - in desperation with my painful shoulder, and a few minutes pulse-checking and tongue-inspecting later, I got this: Your metabolism is like a belligerent, ageing dog, unwilling to go for a walk. Im affronted, which seems to spur the Chinese-medicine therapist on: You are a tortoise when you should be a hare. Or at least a rabbit. Right. Im too polite to tell her to stop the animal metaphors, but Im concerned. I do feel sluggish, but then doesnt everyone? Or perhaps everyone doesnt feel like this and I am indeed a tortoise.

The word metabolism is bandied about all the time as women we decide the type of metabolism we have when were teenagers, and this notion sticks. Increasingly, though, its being seen as one of the pillars of preventative medicine - that current health buzz phrase. Its a major shift in perception for doctors and patients alike. Its vital to recognise the warning signs your body is giving you and act to prevent avoidable damage. You can outfox ageing, declares Dr Sara Gottfried, epigenetics expert and author of the New York Times bestseller The Hormone Cure, as well as a new book enticingly titled Younger. Certainly, it feels compelling to ease the gradient and speed of hormonal decline to protect heart and bone health and OK, I admit it, to stave off a middle-age spread rather than tackling it once it appears.

But it occurs to me that I still dont really know what metabolism actually means. The dictionary definition is uninspiring: The chemical processes within a living organism in order to maintain life. I mention it to my psychologist friend Nicole Sihera, who rings later that day. Well, its easier to blame metabolism than take responsibility for ourselves, isnt it? Its called a self-serving bias, she says. Of course, it does feel very unfair when you see someones Instagram account where they spring out of bed at 6am every day, citing the power of positivity and theres not a bloated stomach or podgy arm in sight. Its enough to make me reach for a pain au raisin and blame my metabolism, but I suspect theres more at play.

The fact is, I do feel lethargic in the mornings, even after a good nights sleep, and my weight has crept up by several kilos in the past few years despite no obvious change in my diet. I drink more alcohol than I used to and am probably not as active. My first thought is to have a full fitness analysis to get some truths. I decide to book in with head trainer and sports-medicine specialist Luke Worthington at the Third Space and make a mental note to be as transparent with him as I can.

I walk in to discover that Luke is an Adonis and I am immediately disinclined to reveal anything, especially not my suspected too-high body-fat percentage. I know youd like me to tell you that people can have a fast or a slow metabolism but that isnt the case, he says. The differences between our metabolic rates are marginal, to say the least. In fact, the number of calories we need is highly correlated with lean muscle mass. The higher the muscle mass, the higher the metabolic rate. This is why men can eat more. Its also a main factor in why we put on weight as we age, because our muscle mass declines. Well, that isnt the answer I wanted. I rail at him, giving him anecdote upon anecdote about the girl we all know who has Dairy Milk and lattes for breakfast but is a size eight. Luke listens patiently and says: The very best advice I can give you is to start weight-bearing exercise. The tipping point for muscle decline is 30. By 40 you start to see the visible physical effects unless you put in the work. The benefits to the body are numerous, not least an increased sense of energy and wellbeing.

I undergo a full scan, which enthusiastically spews out all kinds of stats about the state of my body. I am less than wowed. My magic personal metabolic rate is 1,424 calories, the number that my body would need to keep going each day if I just sat still. For comparison purposes, Luke tells me that his gym-bunny colleague, who is a similar age and height but has a higher lean muscle mass than me, has a personal base rate of 1,600. Theres a handful of nuts in it, calorifically speaking. Luke does crack and say there are other factors, which can be implicated in a feeling of sluggishness that we commonly call a slow metabolism, and I pounce on them, disliking myself for my desire for a quick fix. Thyroid function plays a role, as do insulin response and hormone profile, all of which can be affected by age. But if we eat well and exercise regularly, then much of this negative change is avoided, he explains. My next move, then, is to book in for blood tests to see if hormone function is at play.

Its no coincidence the majority of my patients are over 40 and report the same unhappy triumvirate: fatigue, a sluggish digestion and weight gain, says Dr Sohre, a GP-turned-private-wellness doctor from the Omniya clinic in London. The common factor is a changing hormone profile which can have a negative effect on our wellbeing and certainly influences our metabolism. Quite literally we start to feel less energetic. I undertake a sweep of tests to determine the state of my hormones. Testosterone, which women need to feel vital and maintain muscle mass, is often the first to fall, Sohre continues. I ask what metabolism means to her. For me, it means how healthy we feel and how well we process what we eat. Weve all had that heavy feeling after a meal that, for some, can last for days. I believe improving gut health, optimising hormone levels before the crisis of menopause and eating a healthy diet is the key to getting our metabolic processes firing on all cylinders.

While I wait for the results, I throw myself into some gym visits. I spend time on the weight machines because Luke Worthington and Dr Sohre were both unequivocal: muscle equals metabolic oomph. I tell myself Ill reap the rewards of the afterburn the brilliantly fizzy metabolic term for the two-hour period after exercise when the metabolic rate is proven to increase two- to threefold. Exercise increases metabolism, says Dr Thomas Barber, an obesity researcher and associate professor of clinical endocrinology at the University of Warwick, but it doesnt have to be strenuous. Just by walking about, youre boosting your metabolism and improving health. Weve found that the process of simply contracting a muscle releases beneficial hormone signals called myokines, he explains.

Results day, and Dr Sohre draws a circle on a piece of paper, placing the words thyroid, cortisol, insulin, female hormones around the outside. Each of these will impact your wellbeing and all are mutually dependent. So, for example, a waning thyroid will drain the bodys progesterone production, and a body pumping out the stress hormone cortisol will drain the thyroid, she explains. Results bands for blood tests are typically quite broad. If you were being assessed in the NHS, you would be told you are OK. Theres a pause. But Im looking for optimum health and all of your results are in the bottom third of these reference bands. Your thyroid function isnt clinically abnormal but with levels like this at your age I would expect you to feel the cold more than most, accumulate fat on your tummy and be fatigued. Yes, yes and yes. Your results are clearly sub-optimum and only headed in one direction without intervention. Im starting to feel that the grim reaper will lurch out of the supplies cupboard. No one wants the blood results of a septuagenarian, not even a septuagenarian.

Dr Sohre lifts the mood with her can-do attitude and a plan of action that includes a high-strength thyroid-support supplement, which I am to take as religiously as a medicine to see if we can pep it up without recourse to a prescription for something stronger. A well-functioning thyroid means feeling rested on waking, an efficient digestion and the body basically running more sparkily. I resist knocking back the whole bottle right there at her desk. Im also dispensed a bio-identical progesterone hormone to top up my waning supplies to balance my oestrogen, which she promises will make me feel less grumpy, less puffy and more energetic. Lastly, I am prescribed DHEA to bolster my below-average results. Its the mother hormone made in the adrenal glands. It manages the metabolic processes in the body and cascades to make lots of other hormones, and dwindles with age. By 70 we make around 20 per cent of what we make in our twenties, explains Dr Sohre. DHEA production is also hampered by stress because the body diverts attention to pumping out cortisol, so the stressed-out middle aged are hardest hit. DHEA is considered by many to be a panacea for all ageing ills and is available over the counter in many countries but not in Britain. I realise I am clutching the bottle like Gollum with his ring.

I leave Omniya feeling optimistic, reflecting on the decision Ive made to take medication to optimise my wellbeing rather than treat illness. Its quite clear that metabolism is more than just a weight-gain/weight-loss stooge. Its a catch-all for all the biochemical reactions happening in the body and the trick is to set the conditions to help it flourish. So dont question whether yours is fast or slow, ask instead: is it functioning well?

The fast lane Your thyroid is the main driver of your metabolism. Look after it. Natures Plus Ageloss Thyroid Support, 31 for a months supply, at Amazon.co.uk or Omniya.co.uk

Listen to your body If youve slowed down, think about a body MOT with a preventative medicine specialist. Metabolism & Energy consultation with Dr Sohre at Omniya (3a Montpelier Street, SW7), 250

Help your body burn energy efficiently Healthy gut flora have been proven to support metabolic processes from insulin sensitivity to the livers ability to metabolise fat, explains nutritional therapist Kerry Beeson. Optibac Probiotics Extra Strength, 22.99, Optibacprobiotics.co.uk

Cooling the body induces a metabolic kick The latest fad is to lock yourself in a cryo chamber at -90C to burn calories, heal injuries, pump up the endorphins and give your body a turbo boost. I left bouncing around like a teenager. 95 per session, at 111cryo.com

Metabolism is like moving a boulder Getting started is the tricky part, then momentum takes over. For impetus, drink strong green tea, which has thermogenic properties, and take a mood-enlivening supplement: try Higher Nature Drive (18.30, Victoriahealth.com) which provides the co-factors for energy, balanced brain chemistry and get up and go.

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What Is Metabolism? - Vogue.co.uk

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The Independent News

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Boston, MA, May 13, 2017 (UroToday.com) A series of studies evaluating the relationship between shift work,sleep disorders and a mans urologic health will be presented at a special press conferenceduring the 112th Annual Meeting of the American Urological Association (AUA). Howard L. Adler,MD, clinical associate professor of urology and medical director of the prostate care program atStony Brook Medicine, Stony Brook, NY, will moderate the session, which will take place onSaturday, May 13 at 10:30 a.m. in the Boston Convention & Exhibition Center in Boston, MA. Shift work is known for having unique demands that set it apart from other jobs with traditionaldaytime working hours. It is also known for having such benefits as better pay or theconvenience of not needing child care; however, new studies show the downside to men whoregularly work hours outside of a 7 am. 6 p.m. workday may include an increased risk ofhypogonadal or low-T symptoms, altered semen parameters (e.g., sperm count, motility) andincreased lower urinary tract symptoms (LUTS).

Study Details

Shift Workers with Shift Work Sleep Disorder Have Increased Lower Urinary Tract Symptoms(#MP13-12): Previous studies suggest non-standard male shift workers have an increased risk ofLUTS, which can include frequency or urgency of urination, reduced urine flow, painful urinationor a sensation of incomplete emptying. They also suggest these workers are at an increased riskfor developing shift work sleep disorder (SWSD), a primary circadian rhythm disorder thatdisrupts the bodys internal clock. Utilizing questionnaires from men who presented to a singleandrology clinic between July 2014 and September 2016, researchers set out to examine theassociation between SWSD and LUTS in shift workers. The study population included 2,487 men,of whom 37 percent were diagnosed with SWSD. Each participants work schedule, SWSD riskand LUTS (International Prostate Symptom Score (IPSS) were examined. The impact of nonstandardshift work and SWSD on IPSS score was also assessed using ANOVA and linearregression.

Results showed:

Shift workers diagnosed with SWSD have worse LUTS than those without SWSD. Poor sleep habits, rather than shift work itself, contribute to worse LUTS. Modifying work and sleep schedules may reduce risk for SWSD and subsequent LUTS.

Study Details

Increased Risk of Hypogonadal Symptoms in Shift Workers with Shift Work Sleep Disorder(#MP91-06): Men with hypogonadism have low testosterone levels accompanied by physicalsymptoms such as erectile dysfunction, decreased muscle mass, low sex drive and troublesleeping. In an effort to determine whether a relationship exists between non-standard shiftwork and hypogonadal symptoms, researchers examined data from nearly 2,500 men who werepatients at an andrology clinic between July 2014 and September 2016. Seven hundred sixty-sixmen worked non-standard shifts, and 282 were diagnosed with SWSD. The men completedquestionnaires about their shift work schedule, SWSD risk and hypogonadal symptoms(Androgen Deficiency in the Aging Male (qADAM) questionnaire). The impact of non-standardshift work and SWSD on responses to qADAM was then assessed utilizing ANOVA and linearregression.

Results showed:

Shift workers with SWSD have lower testosterone levels and worse hypogonadal symptoms than daytime workers. Poor sleep habits caused by SWSD may contribute to more severe hypogonadal symptoms in non-standard shift workers. SWSD was independently associated with lower testosterone levels when controlling for age, comorbidities and history of testosterone supplementation.

Study Details

Shift Work is Associated with Altered Semen Parameters in Infertile Men (#: PD13-08):Recognizing shift work negatively impacts circadian rhythms and the hypothalamic-pituitarygonadal(HPG) axis, an integral regulator of spermatogenesis, researchers in Texas set out tostudy the impact of shift work on semen parameters and reproductive hormones in infertilemen. Participants included men who were not able to achieve pregnancy within 12 months, andhad no known genetic or obstructive causes of infertility, as well as, men who had fathered achild within the last five years. Nearly 200 men: 75 infertile shift workers, 98 infertile non-shiftworkers and 27 fertile controls were compared.

Results showed:

Sperm density, total motile count (TMC) and testosterone levels were lower in shiftworkers. No differences in semen volume, sperm motility, leutinizing hormone or follicle stimulating hormone were observed. Infertile shift workers have worse semen parameters than non-shift workers, which is consistent with alterations in the HPG axis observed in shift workers.

Study Details

The Relationship Between Sleep Disorders and Lower Urinary Tract Symptoms: Results fromthe National Health and Nutrition Examination Survey (NHANES) (#: MP13-15): By examiningthe NHANES database, researchers sought to investigate the frequency of LUTS in men, with andwithout such sleep disorders as obstructive sleep apnea and insomnia. Researchers examinedthe NHANES database over a two-year period and included men ages 18-70 who completedsleep questionnaires in addition to prostate and kidney forms. Physician-diagnosed sleepdisorders were self-reported by patients and statistical analyses were used to compare groups.

Results showed:

Of the 6,158 men who completed the survey questions, seven percent reported a sleep disorder. Men with sleep disorders, particularly obstructive sleep apnea, have increased nocturia and are more likely to experience daytime LUTS. Older age, Caucasian race, elevated BMI and increased comorbidity score are factors associated with an increased risk of LUTS in men with sleep disorders. Men with obstructive sleep apnea were more likely to experience bothersome daytime LUTS compared to men with other sleep disorders.

These findings demonstrate how sleep disruption and shift work can negatively impact a mansurologic health, said Dr. Adler. The improved understanding about the role sleep plays incontributing to or worsening lower urinary tract symptoms, male infertility and low testosteronecan lead to more effective diagnosis and treatment options.

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AUA 2017: The Effect of Shift Work on a Man's Sexual and Urologic Health - UroToday

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May 17, 2017 Images of heart muscle cells derived from induced pluripotent stem cells. Credit: Q. Duan et al., Science Translational Medicine (2017)

A team of researchers at the Gladstone Institutes uncovered a new strategy to treat heart failure, a leading contributor to mortality and healthcare costs in the United States. Despite widespread use of currently-approved drugs, approximately 40% of patients with heart failure die within 5 years of their initial diagnosis.

"The current standard of care is clearly not sufficient, which highlights the urgent need for new therapeutic approaches," said Saptarsi Haldar, MD, an associate investigator at Gladstone and senior author of a new study featured on the cover of the scientific journal Science Translational Medicine. "In our previous work, we found that a drug-like small molecule called JQ1 can prevent the development of heart failure in mouse models when administered at the very onset of the disease. However, as the majority of patients requiring treatment already have longstanding cardiac dysfunction, we needed to determine if our strategy could also treat established heart failure."

As part of an emerging treatment strategy, drugs derived from JQ1 are currently under study in early-phase human cancer trials. These drugs act by inhibiting a protein called BRD4, a member of a family of proteins called BET bromodomains, which directly influences heart failure. With this study, the scientists found that JQ1 can effectively treat severe, pre-established heart failure in both small animal and human cell models by blocking inflammation and fibrosis (scarring of the heart tissue).

"It has long been known that inflammation and fibrosis are key conspirators in the development of heart failure, but targeting these processes with drugs has remained a significant challenge," added Haldar, who is also a practicing cardiologist and an associate professor in the Department of Medicine at the University of California, San Francisco. "By inhibiting the function of the protein BRD4, an approach that simultaneously blocks both of these processes, we are using a new and different strategy altogether to tackle the problem."

Currently available drugs used for heart failure work at the surface of heart cells. In contrast, Haldar's approach goes to the root of the problem and blocks destructive processes in the cell's command center, or nucleus.

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"We treated mouse models of heart failure with JQ1, similarly to how patients would be treated in a clinic," said Qiming Duan, MD, PhD, postdoctoral scholar in Haldar's lab and co-first author of the study. "We showed that this approach effectively treats pre-established heart failure that occurs both after a massive heart attack or in response to persistent high blood pressure (mechanical overload), suggesting it could be used to treat a wide array of patients."

Using Gladstone's unique expertise, the scientists then used induced pluripotent stem cells (iPSCs), generated from adult human skin cells, to create a type of beating heart cell known as cardiomyocytes.

"After testing the drug in mice, we wanted to check whether JQ1 would have the same effect in humans," explained co-first author Sarah McMahon, a UCSF graduate student in Haldar's lab. "We tested the drug on human cardiomyocytes, as they are cells that not only beat, but can also trigger the processes of inflammation and fibrosis, which in turn make heart failure progressively worse. Similar to our animal studies, we found that JQ1 was also effective in human heart cells, reaffirming the clinical relevance of our results."

The study also showed that, in contrast to several cancer drugs that have been documented to cause cardiac toxicity, BRD4 inhibitors may be a class of anti-cancer therapeutics that has protective effects in the human heart.

"Our study demonstrates a new therapeutic approach to successfully target inflammation and fibrosis, representing a major advance in the field," concluded Haldar. "We also believe our current work has important near-term translational impact in human heart failure. Given that drugs derived from JQ1 are already being tested in cancer clinical trials, their safety and efficacy in humans are already being defined. This key information could accelerate the development of a new heart failure drug and make it available to patients more quickly."

Explore further: Heart failure is as 'malignant' as some common cancers

More information: Q. Duan el al., "BET bromodomain inhibition suppresses innate inflammatory and profibrotic transcriptional networks in heart failure," Science Translational Medicine (2017). stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aah5084

A new analysis finds that, despite advances in care, men and women with a diagnosis of heart failure continue to have worse survival rates than patients with certain common cancers.

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Researchers have completed a randomized clinical trial in patients with heart failure with preserved ejection fraction (HFpEF), which currently has no effective treatment for reducing morbidity and mortality.

A new analysis describes different classifications of patients who are hospitalized with acute heart failure based on various characteristics, which may help guide early decisions regarding triage and treatment.

(HealthDay)Patients with rheumatoid arthritis (RA) have increased risk of heart failure, according to a study published in the March 14 issue of the Journal of the American College of Cardiology.

In the largest German survey on heart failure to date, investigators found that the overall awareness of heart failure has not increased over the past decade and is not at a satisfactory level.

Shortness of breath is the No.1 complaint of people suffering from heart failure. Now a University of Guelph researcher has discovered its surprising cause - and an effective treatment - in a groundbreaking new study.

A team of researchers at the Gladstone Institutes uncovered a new strategy to treat heart failure, a leading contributor to mortality and healthcare costs in the United States. Despite widespread use of currently-approved ...

Although the absolute difference in U.S. county-level cardiovascular disease mortality rates have declined substantially over the past 35 years for both ischemic heart disease and cerebrovascular disease, large differences ...

Waist-to-hip ratio may be a stronger indicator of some cardiovascular illnesses than the commonly-used measure BMI, according to a new UCL-led study.

New research has found that genetic differences in antibody genes alter individuals' susceptibility to rheumatic heart disease, a forgotten inflammatory heart condition known as 'RHD' that is rife in developing countries.

People who use commonly prescribed non-steroidal anti-inflammatory drugs (NSAIDs) to treat pain and inflammation could be raising their risk of having a heart attack, as early as in the first week of use and especially within ...

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"Creative Medical Technology Holdings will develop this patent through the same process that we are using for our clinical-stage Caverstem procedure for erectile dysfunction," stated Timothy Warbington, President and Chief Executive Officer of the Company. "We plan to identify and engage key opinion leaders who will lead clinical trials, which will serve as the basis for accelerated commercialization."

The Company is currently running a clinical trial using autologous non-manipulated bone marrow stem cells for patients suffering from erectile dysfunction that are non-responsive to standard approaches such as Viagra.Once the trial is completed, the results will serve as the basis for marketing of disposables utilized in administration of stem cells.

"Although numerous companies are injecting stem cells directly into the disc, direct injection may only cause temporary benefit because the root cause of the pathology, in our opinion, is the reduced blood supply," stated Dr. Amit Patel, Director of Thoracic Surgery at University of Miami and co-founder of Creative Medical Technology Holdings. "By recreating in the microenvironment of the lower back the same thing that we do in atherosclerotic heart patients, we believe we have a novel way to treat this terrible condition that wreaks havoc on our health care system."

Several studies have shown that administration of stem cells possesses a therapeutic effect in cardiac conditions associated with poor circulation by stimulation of new blood vessel production, a process termed "angiogenesis".The current patent covers stimulation of angiogenesis in the lower back using mesenchymal stem cells.These cells can be used from the same patient, which is considered an "autologous therapy" as well as using stem cells in a universal donor manner, which is termed "allogeneic".

"The acquisition of this patent not only positions the company to expand into the disc degenerative space, but also provides a powerful platform for collaboration with other companies that are administering regenerative cells directly into the nucleus pulposus of the disc," commented Thomas Ichim, Ph.D., Chief Scientific Officer of the Company and inventor of the technology. "Stem cells are like seeds, they need to be planted into fertile soil. We feel that in certain patients it is essential to treat the lumbar ischemia, which is present in some patients suffering from disc degenerative disease, which will then allow the stem cells administered directly in the disc to perform their regenerative effects."

About US

Creative Medical Technology Holdings, Inc. is a clinical-stage biotechnology company with two focus areas; 1) personalized stem cell procedures for sexual dysfunction and infertility, and 2) universal, off-the-shelf amniotic fluid-based stem cells that possess superior healing potential without negative medical or ethical issues. Through our own research and collaborations with leading academic institutions, we have developed proprietary protocols, built an extensive intellectual property portfolio, developed complete treatment offerings for erectile dysfunction and are performing ground-breaking research with our amniotic fluid-based stem cell.

For additional information visit http://www.CREATIVEMEDICALTECHNOLOGY.com

Forward-Looking StatementsThis release may contain "forward-looking statements." Forward-looking statements are identified by certain words or phrases such as "may", "aim", "will likely result", "believe", "expect", "anticipate", "estimate", "intend", "plan", "contemplate", "seek to", "future", "objective", "goal", "project", "should", "will pursue" and similar expressions or variations of such expressions. These forward-looking statements reflect the Company's current expectations about its future plans and performance. These forward-looking statements rely on a number of assumptions and estimates which could be inaccurate and which are subject to risks and uncertainties. Actual results could vary materially from those anticipated or expressed in any forward-looking statement made by the Company. Please refer to the Company's most recent Forms 10-Q and 10-K and subsequent filings with the SEC for a further discussion of these risks and uncertainties. The Company disclaims any obligation or intent to update the forward-looking statements in order to reflect events or circumstances after the date of this release.

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/creative-medical-technology-holdings-to-expand-into-10-billion-dollar-per-year-lower-back-pain-market-with-acquisition-of-issued-us-stem-cell-patent-300459902.html

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Heavy increases in obesity have led to an epidemic of various heart diseases, including cardiac arrests and even strokes. These dangers have compelled doctors and research specialists to seek out new ways of managing these problems. One method that has been getting a lot of attention is regenerative medicine.

This treatment method, while occasionally controversial, shows an incredible potential that could solve many serious health problems. Specialists like Dr. Cameron Clokie, a health expert with decades of experience, are currently trying to find ways to make this treatment method more accepted by those who oppose it.

The Potential for Serious Health Benefits is Huge

Regenerative medicine is the use of stem cells and other regeneration items to promote more efficient healing. Dr. Cameron Clokie has preached about the effectiveness of this treatment method for years. And it seems like the rest of the world is finally catching up with him and others like him. For example, a recent study found that stem cells could help manage cardiac and nervous system diseases.

The careful use of stem cells could regenerate damaged heart tissues and help a person avoid heart attacks and other serious problems. Even more promising, stem cells could be used to help repair nerve damage that would otherwise leave a person paralyzed for life.

Stem Cell Research Could Save Lives

Think of the stem cells in your body as building blocks that will take whatever shape is necessary. They can become heart cells and patch a hole in this vital organ. However, they could also become spinal cells and repair severe damage to this crucial part of the body.

The possibilities associated with stem cells could be potentially limitless. As they can be manipulated to take the form of any cell, they could be used to treat a variety of serious health problems. For example, they could become white blood cells and fight serious viral problems. In fact, they could even be used to treat life-threatening diseases like AIDS.

One of the understated benefits of regenerative medicine is the way that it uses actual cells from your body. Think of the problems the medical world has had with artificial hearts. While they can be beneficial to many people, they are often rejected by the fickle body as an intruder. However, creating a working heart with your body's stem cells would eliminate that problem.

Why? Your body would recognize the heart's cells as coming from you and would accept it more readily. As a result, you could get a new (and real) heart to replace a severely damaged one.

Profit Levels Could Also Be High

One thing that has interested many people about regenerative health and stem cell research is the potential for huge profits. Many health experts have tried to stress the ways that regenerative health could help boost the world's economy. For example, a recent study on the financial state of this market found that it had an $18.9 billion global impact.

Even more shocking, it was projected to hit $53 billion by 2021. The major focus of this market would be in bone and joint reconstruction. The United States was expected to potentially make the largest profits in this area, which is something Dr. Cameron Clokie has emphasized in the past.

However, the European market is projected to be even bigger if the currently somewhat stagnant American regenerative market is held back by restrictive regulations or laws. In this way, well-meaning politicians could deny their constituents access to lifesaving treatments and severely impact the market at the same time.

Final Thoughts

Regenerative medicine of the type proposed by Dr. Cameron Clokie and others like him could transform the medical world. While the protests of people who find stem cells wrong are understandable, the major benefits of using them cannot be ignored.

This fact is why it is so important to help specialists like Dr. Cameron Clokie get the help they need to promote regenerative medicine breakthroughs. In this way, it is possible to solve serious health dangers.

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Canadian Doctors Like Cameron Clokie Are The Innovators Behind The New Era of Regenerative Medicine - French Tribune

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Potential for a new supply line

Burger/Phanie/REX/Shutterstock

By Jessica Hamzelou

The stem cells that produce our blood have been created in the lab for the first time. These could one day be used to treat people who have blood diseases and leukaemia with their own cells, rather than bone marrow transplants from a donor. They could also be used to create blood for transfusions.

This is a very big deal, says Carolina Guibentif at the University of Cambridge, who was not involved in the research. If you can develop [these cells] in the lab in a safe way and in high enough numbers, you wouldnt be dependent on donors.

In a healthy adult, blood stem cells are found in bone marrow, where they replenish the supply of red and white blood cells and platelets. They are sort of master cells, says George Daley at Harvard Medical School.

When these cells dont work properly, they fail to maintain an adequate supply of blood cells. As a result, not enough oxygen reaches the bodys tissues. This can cause serious disease if organs such as the heart are affected. Blood stem cells can also be wiped out by chemotherapy for leukaemia and other cancers.

People with these disorders tend to be treated with bone marrow complete with blood stem cells from a healthy donor. The difficulty is finding a match. There is a one in four chance of achieving this from a healthy sibling, but the odds are slashed to one in a million if a stranger needs to be found, says Daley.

In an attempt to create blood stem cells in the lab, Daley and his colleagues started with human pluripotent stem cells which have the potential to form almost any other type of body cell.

The team then searched for chemicals that might encourage these to become blood stem cells.

After studying the genes involved in blood production, the researchers identified proteins that control these genes and applied them to their stem cells.

They tested many combinations of the proteins, and found five that worked together to encourage their stem cells to become blood stem cells. When they put these into mice, they went on to produce new red and white blood cells and platelets. Its very cool, says Daley. Were very excited about the results.

A separate team has achieved the same feat with stem cells taken from adult mice. Raphael Lis at Weill Cornell Medical College in New York and his colleagues started with cells taken from the walls of the animals lungs, based on the idea that similar cells in an embryo eventually form the bodys first blood stem cells. The team identified a set of four factors that could encourage these lung stem cells to make them.

Both sets of results represent a breakthrough, says Guibentif. This is something people have been trying to achieve for a long time, she says. By working with adult mouse epithelial cells, Lis and his team show that the feat could potentially be achieved with cells taken from an adult person. Daleys team used human stem cells that could in theory be made from skin cells, bolstering the prospect that lab-made human blood could be next.

The lab-made stem cells are not quite ready to be used in people just yet, says Daley. Although all of his mice were healthy throughout the experiments, there is a risk that the cells could mutate and cause cancer. And the cells are not quite as efficient at making blood as those found in the body.

But once Daley and his team have honed their procedure, they might be able to make platelets and red blood cells for hospital use. These cell types dont have a nucleus, so are unable to divide and potentially cause cancer. He hopes this procedure could be used within the next couple of years.

Eventually, Daley hopes his cells could be used to create whole blood suitable for transfusions. Not only would such a supply be more reliable than that from donors, but it would also be free of disease. When new pathogens like Zika pop up, you have to make sure that blood is safe, says Daley. Wed be able to have more quality control.

Journal references: Nature, DOI: 10.1038/nature22326; Nature, DOI: 10.1038/nature22370

Read more: Synthetic bone implant can make blood cells in its marrow; Lab-grown blood given to volunteer for the first time

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Human blood stem cells grown in the lab for the first time - New Scientist

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Science Daily

Another reason to exercise: Burning bone fat a key to better bone health Science Daily It could be that when fat cells are burned during exercise, the marrow uses the released energy to make more bone. Or, because both fat and bone cells come from parent cells known as mesenchymal stem cells, it could be that exercise somehow stimulates ... and more »

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Islamabad

The Ministry of National Health Services signed a Memorandum of Understanding with the Armed Forces Bone Marrow Transplant Centre here Thursday for provision of bone marrow transplant facility to the general public and federal government employees and their families, along with Armed Forces personnel and their families and defence paid employees.

Under the MOU, the National Institute of Blood and Marrow Transplant shall be established at the Armed Forces Bone Marrow Transplant Centre and will be designated as the National Institute of Blood and Marrow Transplant (NIBMT). This new facility will broaden the scope of the hospital, so that bone marrow/stem cell transplant can be extended to federal government employees and the general public. It will also serve to extend training facilities in the field of Bone Marrow Transplant and Clinical Haematology.

The MOU was signed on behalf of National Health Services by Director General Health Dr. Assad Hafeez whereas Major General Tariq Mehmood Satti Commandant Armed Forces Bone Marrow Transplant Centre, Rawalpindi, signed on behalf of his organization. Commandant of the Armed Forces Institute of Pathology Maj. Gen. Parvez Ahmed was also present on the occasion.

Speaking on the occasion, the Secretary of the Ministry of Health Services Muhammad Ayub Shaikh expressed gratitude to the Commandant of AFIP and AFBMPC for their efforts in making the MOU possible. This noble initiative will benefit a large number of patients, he projected. Major General Parvez Ahmed elaborated the efforts and initiatives taken to make the MOU possible.

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Bone marrow transplant facility to be available to public, government employees - The News International

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Jonathan Pitre in a 2015 TSN profile.

This time, it worked.

Suffering from a severe form of epidermolysis bullosa (EB), an incurable genetic condition which causes the skin to blister and create painful wounds, Pitre, who turns 17 next month, was given the moniker Butterfly Boy due to his delicate skin.

EB can be fatal, with many people who have severe EB dying from skin cancer in their twenties. Pitre underwent his second stem cell transplant procedure at the University of Minnesota Masonic Childrens Hospital, a pioneer in treating EB though stem cell transplants.

Paediatric hematoligist-oncologist with the University of Minnesota Jakub Tolar calls EB the worst disease youve never heard of, as it affects only one in 20,000 people. Research by Tolar and his colleagues led to the discovery that bone marrow transplantation, a procedure typically used to treat blood cancers in the bone marrow such as leukemia, could benefit those with EB.

This had never been done before, says Tolar, who directs the U of Ms Stem Cell Institute, in a press release. I didnt know it at the time we started this research 10 years ago, but it opened a totally new field in transplantation biology.

Stem cell transplants involve a persons blood-forming stem cells (immature cells that can become various types of specialized cells in the body, in this case, becoming different types of blood cells) from the bone marrow and replacing them with healthy stem cells.

For Pitre, his earlier bone marrow transplant last October proved unsuccessful as doctors learned that his own stem cells had recolonized his bone marrow. This time around, the results look more promising. Pitres mother, Tina Boileau, who was the donor, is now full of joy and relief, according to an Ottawa Citizen report, which states that newly created white blood cells in Pitres system contain a pair of X chromosomes, indicating that they came from Boileaus donated cells.

This is the best news ever, the best Mothers Day gift, said Boileau. Jon is full of me. He doesnt have any T-cells that are his.

Its been over 30 years since bone marrow cells were first used to treat cancer, but recent advances have shown the potential application of stem cell transplantation for a variety of diseases and conditions, from brain and spinal cord injury to neurodegenerative diseases like Alzheimers to HIV/AIDS. Researchers at Cardiff University in Wales, for example, have just announced commencement of stem cell transplants for patients with Huntingtons disease.

The Ontario government has just announced $32 million in new funding to help shorten the long wait times for stem cell transplants in the province, meaning that 150 more patients a year will be able to receive transplant therapy. As reported in the Hamilton Spectator, $10 million of the new funds will be going to the Juravinski Hospital and Cancer Centre in Hamilton for a dedicated unit with 15 inpatient and five outpatient beds.

Below: TSN Original: The Butterfly Child

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Ontario teen Jonathan Pitre's second attempt at stem cell transplant is a success - Cantech Letter

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Scientists have healed severe bone fractures in pigs by blasting tiny bubbles with ultrasound in the animals bones. The technique encourages the pigs bodies to regenerate themselves, and could one day be used to help humans especially the elderly heal dangerous bone injuries.

Broken bones are common: you wrap an arm or wrist in a cast and the bone eventually heals on its own. But sometimes, people have nonunion fractures, meaning bones fail to produce new bone tissue and dont heal properly. There are about 100,000 cases of this in the United States every year. One solution is bone grafts, or bone transplants using donated marrow, but this procedure is invasive and there is a risk that the body will reject the marrow. Another solution is to use viruses to deliver bone morphogenetic proteins (BMPs) that encourage the bodys own stem cells to create more bone marrow. But using a virus can have negative side effects like inflammation.

In a study published today in Science Translational Medicine, scientists healed a 0.4-inch fracture in pigs in eight weeks without invasive surgery. Going from something invasive to something like this that potentially could be an outpatient procedure has been the holy grail in orthopedics, says Edward Schwarz, director of the University of Rochesters Center for Musculoskeletal Research, who was not involved with the study. He adds that, though these nonunion fractures arent the most common health problem, theyre a serious one. People are shocked when I tell them that the life expectancy with a nonunion fracture is shorter than with pancreatic cancer, he says. Were like horses. If we cant get up and walk again, then were done.

In the study, the researchers first caused a 0.4-inch fracture in the shins of 18 minipigs. Then, they inserted a biodegradable scaffolds into the broken shins, says co-author Gadi Pelled, a professor of surgery at Cedars-Sinai Medical Center. The scaffold helped support bone stem cells in the area. The scientists let the stem cells migrate and populate over the scaffold for two weeks but that wast enough. The stem cells had to be triggered to actually heal the injury. So the scientists injected microbubbles mixed with bone morphogenetic proteins. Immediately after the injection, they applied ultrasound, which stimulated the BMPs to enter into the stem cells and activate them.

The stem cells then turned into bone cells and healed the fracture after eight weeks. This method doesnt have the side effects associated with using viruses, and the fact that it uses the bodys own stem cells means theres no risk of rejection, says co-author Zulma Gazit, also at Cedars-Sinai. This ultrasound and microbubbles combo has already been approved by the Food and Drug Administration and is often used in radiology, so the new technique could be readily approved for use in humans.

Next, says Pelled, the team is studying whether the same technology can also work with tissues like ligaments; they gathering more comprehensive information. Before we move forward into humans, we need to determine that this technology is safe, says Pelled. Theyre hopeful that a clinical trial is on the way.

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Blasting tiny bubbles at broken pig bones makes them heal on their own - The Verge

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Washington D.C., May 18, 2017 / 03:02 pm (CNA/EWTN News).- Within the next 10-20 years, a new and controversial fertility technology called in vitro gametogenesis could make it possible to manipulate skin cells into creating a human baby.

However, this groundbreaking research has caused push-back from some critics, like Fr. Tadeusz Pacholczyk, director of education at the National Catholic Bioethics Center, who says IVG would turn procreation into a transaction.

IVG extends the faulty logic of IVF by introducing additional steps to the process of manipulating the origins of the human person, in order to satisfy the desires of customers and consumers, Fr. Pacholczyk told CNA in an email interview.

The technology also offers the possibility of introducing further fractures into parenthood, distancing children from their parents by multiplying the number of those involved in generating the child, so that 3-parent embryos, or even more parents, may become involved, he continued.

IVG has been successfully tested by Japanese researchers on mice, which produced healthy babies derived from skin cells.

The process begins by taking the skin cells from the mouses tail and re-programing them to become induced pluripotent stem cells. These manipulated cells are able to grow different kinds of cells, and are then used to grow eggs and sperm, which are then fertilized in the lab. The resulting embryos are then implanted in a womb.

Although similar to in vitro fertilization, IVG eliminates the step of needing pre-existing egg and sperm, and instead creates these gametes.

But many experts in the reproductive field are skeptical of its potential outcomes and ethical compromises.

It gives me an unsettled feeling because we dont know what this could lead to, Paul Knoepfler, a stem cell researcher at the University of California, Davis, told the New York Times.

Knoepfler noted that some of the potential repercussions of IVG could turn into cloning or designer babies. Other dangers could include the Brad Pitt scenario, in which celebritys skin cells retrieved from random places, like hotel rooms, could be used to create a baby.

Potentially anyones skin cells could be used to create a baby, even without their knowledge or consent.

In an issue of Science Translational Medicine earlier this year, a trio of academics a Harvard Law professor, the dean of Harvard Medical School, and a medical science professor at Brown wrote that IVG may raise the specter of embryo farming on a scale currently unimagined, which might exacerbate concerns about the devaluation of human life.

They added that refining the science of IVG to the point of clinical use will involve the generation and likely destruction of large numbers of embryos from stem cellderived gametes and the process may exacerbate concerns regarding human enhancement.

Fr. Pacholczyk also pointed to further concerns, saying IVG disrupts the uniqueness of every individuals sex cells.

I.V.G raises additional concerns because of the way it manipulates human sex cells. Our sex cells, or gametes, are special cells. They uniquely identify us, Fr. Pacholczyk stated.

It is most unfortunate that overwhelming parental desires are being permitted to trump and distort the right order of transmitting human life, he continued.

Fr. Pacholczyk said that processes like IVG enable a consumerist mentality that holds that children are projects to be realized through commercial transactions and laboratory techniques of gamete manipulation.

The Catholic Church teaches that IVF and similar reproductive technologies are morally illicit for several reasons, including their separation of procreation from the conjugal act and the creation of embryos which are discarded.

Pope Francis recently spoke out against the destruction of human embryos, saying that no good result from research can justify the destruction of embryos.

Some branches of research use human embryos, inevitably causing their destruction. But we know that no ends, even noble in themselves such as a predicted utility for science, for other human beings or for society can justify the destruction of human embryos, the Holy Father said May 18.

Although IVG has proven successful in mice, there are still some wrinkles that need to be ironed out before it is tested on humans, and will entail years more of tedious bioengineering.

However, Fr. Pacholczyk hopes that potential parents will come to realize that children should not products that can be ordered or purchased by consumers, and should rather be seen as a gift.

Turning commercial laboratories to create children on our behalf is an unethical step in the direction of treating our offspring as objects to be planned and created in the pursuit of parental gratification, rather than gifts received from the Lord.

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This new technology could produce babies from skin cells. And that's bad. - Catholic News Agency

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Science Daily

Approaching a decades-old goal: Making blood stem cells from patients' own cells Science Daily ... lab using pluripotent stem cells, which can make virtually every cell type in the body. The advance opens new avenues for research into the root causes of blood diseases and to creating immune-matched blood cells for treatment purposes, derived ... 'Milestone' in quest to make blood cells: studiesGeo News, Pakistan all 41 news articles »

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Approaching a decades-old goal: Making blood stem cells from patients' own cells - Science Daily

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Precision editing DNA allows for some amazing applications. Ian Haydon, CC BY-ND

Ian Haydon, University of Washington

Theres a revolution happening in biology, and its name is CRISPR.

CRISPR (pronounced crisper) is a powerful technique for editing DNA. It has received an enormous amount of attention in the scientific and popular press, largely based on the promise of what this powerful gene-editing technology will someday do.

CRISPR was Science magazines 2015 Breakthrough of the Year; its been featured prominently in the New Yorker more than once; and The Hollywood Reporter revealed that Jennifer Lopez will be the executive producer on an upcoming CRISPR-themed NBC bio-crime drama. Not bad for a molecular biology laboratory technique.

Two of the CRISPR co-inventors, Emmanuelle Charpentier (middle-left) and Jennifer Doudna (middle-right), rubbing elbows with celebs after receiving the 2015 Breakthrough Prize in Life Sciences. Breakthrough Prize Foundation, CC BY-ND

CRISPR is not the first molecular tool designed to edit DNA, but it gained its fame because it solves some longstanding problems in the field. First, it is highly specific. When properly set up, the molecular scissors that make up the CRISPR system will snip target DNA only where you want them to. It is also incredibly cheap. Unlike previous gene editing systems which could cost thousands of dollars, a relative novice can purchase a CRISPR toolkit for less than US$50.

Research labs around the world are in the process of turning the hype surrounding the CRISPR technique into real results. Addgene, a nonprofit supplier of scientific reagents, has shipped tens of thousands of CRISPR toolkits to researchers in more than 80 countries, and the scientific literature is now packed with thousands of CRISPR-related publications.

When you give scientists access to powerful tools, they can produce some pretty amazing results.

The most promising (and obvious) applications of gene editing are in medicine. As we learn more about the molecular underpinnings of various diseases, stunning progress has been made in correcting genetic diseases in the laboratory just over the past few years.

Take, for example, muscular dystrophy a complex and devastating family of diseases characterized by the breakdown of a molecular component of muscle called dystrophin. For some types of muscular dystrophy, the cause of the breakdown is understood at the DNA level.

In 2014, researchers at the University of Texas showed that CRISPR could correct mutations associated with muscular dystrophy in isolated fertilized mouse eggs which, after being reimplanted, then grew into healthy mice. By February of this year, a team here at the University of Washington published results of a CRISPR-based gene replacement therapy which largely repaired the effects of Duchenne muscular dystrophy in adult mice. These mice showed significantly improved muscle strength approaching normal levels four months after receiving treatment.

Using CRISPR to correct disease-causing genetic mutations is certainly not a panacea. For starters, many diseases have causes outside the letters of our DNA. And even for diseases that are genetically encoded, making sense of the six billion DNA letters that comprise the human genome is no small task. But here CRISPR is again advancing science; by adding or removing new mutations or even turning whole genes on or off scientists are beginning to probe the basic code of life like never before.

CRISPR is already showing health applications beyond editing the DNA in our cells. A large team out of Harvard and MIT just debuted a CRISPR-based technology that enables precise detection of pathogens like Zika and dengue virus at extremely low cost an estimated $0.61 per sample.

Using their system, the molecular components of CRISPR are dried up and smeared onto a strip of paper. Samples of bodily fluid (blood serum, urine or saliva) can be applied to these strips in the field and, because they linked CRISPR components to fluorescent particles, the amount of a specific virus in the sample can be quantified based on a visual readout. A sample that glows bright green could indicate a life-threatening dengue virus infection, for instance. The technology can also distinguish between bacterial species (useful for diagnosing infection) and could even determine mutations specific to an individual patients cancer (useful for personalized medicine).

Feng Zhang, another co-inventor of CRISPR technology, discussing its safety and ethical ramifications. AP Photo/Susan Walsh

Almost all of CRISPRs advances in improving human health remain in an early, experimental phase. We may not have to wait long to see this technology make its way into actual, living people though; the CEO of the biotech company Editas has announced plans to file paperwork with the Food and Drug Administration for an investigational new drug (a necessary legal step before beginning clinical trials) later this year. The company intends to use CRISPR to correct mutations in a gene associated with the most common cause of inherited childhood blindness.

Physicians and medical researchers are not the only ones interested in making precise changes to DNA. In 2013, agricultural biotechnologists demonstrated that genes in rice and other crops could be modified using CRISPR for instance, to silence a gene associated with susceptibility to bacterial blight. Less than a year later, a different group showed that CRISPR also worked in pigs. In this case, researchers sought to modify a gene related to blood coagulation, as leftover blood can promote bacterial growth in meat.

You wont find CRISPR-modified food in your local grocery store just yet. As with medical applications, agricultural gene editing breakthroughs achieved in the laboratory take time to mature into commercially viable products, which must then be determined to be safe. Here again, though, CRISPR is changing things.

A common perception of what it means to genetically modify a crop involves swapping genes from one organism to another putting a fish gene into a tomato, for example. While this type of genetic modification known as transfection has actually been used, there are other ways to change DNA. CRISPR has the advantage of being much more programmable than previous gene editing technologies, meaning very specific changes can be made in just a few DNA letters.

This precision led Yinong Yang a plant biologist at Penn State to write a letter to the USDA in 2015 seeking clarification on a current research project. He was in the process of modifying an edible white mushroom so it would brown less on the shelf. This could be accomplished, he discovered, by turning down the volume of just one gene.

White Agaricus bisporus mushrooms with no browning are more visually appealing. Olha Afanasieva/Shutterstock.com

Yang was doing this work using CRISPR, and because his process did not introduce any foreign DNA into the mushrooms, he wanted to know if the product would be considered a regulated article by the Animal and Plant Health Inspection Service, a division of the U.S. Department of Agriculture tasked with regulating GMOs.

APHIS does not consider CRISPR/Cas9-edited white button mushrooms as described in your October 30, 2015 letter to be regulated, they replied.

Yangs mushrooms were not the first genetically modified crop deemed exempt from current USDA regulation, but they were the first made using CRISPR. The heightened attention that CRISPR has brought to the gene editing field is forcing policymakers in the U.S. and abroad to update some of their thinking around what it means to genetically modify food.

One particularly controversial application of this powerful gene editing technology is the possibility of driving certain species to extinction such as the most lethal animal on Earth, the malaria-causing Anopheles gambiae mosquito. This is, as far as scientists can tell, actually possible, and some serious players like the Bill and Melinda Gates Foundation are already investing in the project. (The BMGF funds The Conversation Africa.)

Most CRISPR applications are not nearly as ethically fraught. Here at the University of Washington, CRISPR is helping researchers understand how embryonic stem cells mature, how DNA can be spatially reorganized inside living cells and why some frogs can regrow their spinal cords (an ability we humans do not share).

It is safe to say CRISPR is more than just hype. Centuries ago we were writing on clay tablets in this century we will write the stuff of life.

Ian Haydon, Doctoral Student in Biochemistry, University of Washington

This article was originally published on The Conversation. Read the original article.

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Gene-editing tool 'CRISPR' gaining massive attention - KMOV.com

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Philippe Huguen/AFP/Getty

A gene mutation that made tomatoes easier to harvest has been identified.

From their giant fruits to compact plant size, todays tomatoes have been sculpted by thousands of years of breeding. But mutations linked to prized traits including one that made them easier to harvest yield an undesirable plant when combined, geneticists have found1.

It is a rare example of a gene harnessed during domestication that later hampered crop improvement efforts, says geneticist Zachary Lippman of Cold Spring Harbor Laboratory in New York. After identifying the mutations, he and his colleagues used CRISPR gene editing to engineer more productive plants a strategy that plant breeders are eager to adopt.

Its pretty exciting, says Rod Wing, a plant geneticist at the University of Arizona in Tucson. The approach can be applied to crop improvement, not just in tomato, but in all crops.

Lippman knows his way around a tomato farm. As a teenager, he spent his summers picking the fruit by hand a chore he hated. Rotten tomatoes. The smell lasts all day long, he says. I would always pray for rain on tomato-harvest day.

But years later, his interest in the genetics that control a plants shape led him back to tomato fields, to untangle the genetic changes that breeders had unknowingly made.

In the 1950s, researchers found a new trait in a wild tomato relative growing in the Galpagos Islands: it lacked the swollen part of the stem called the joint.

Joints are weak regions of the stem that allow fruit to drop off the plant. Wild plants benefit from dropping fruit because it helps seed dispersal. But with the advent of mechanical tomato pickers, farmers wanted their fruit to stay on the plant. Breeders rushed to incorporate the jointless trait into their tomatoes.

This new trait came with a downside. When it was crossed into existing tomato breeds, the resulting plants had flower-bearing branches that produced many extra branches and looked like a broom, terminating in a host of flowers. The flowers were a drain on plant resources, diminishing the number of fruits it produced. Breeders selected for other genetic variants that overrode this defect. But decades later, Lippman's team went looking for the genes behind this phenomenon.

They had previously screened a collection of 4,193 varieties of tomato, looking for those with unusual branching patterns2. From that collection, they tracked down variants of two genes that, together, caused extreme branching similar to what plant breeders had seen. One of the two genes, the team reports in a paper published online in Cell on 18 May, is responsible for the jointless trait1.

The other gene favours the formation of a large green cap of leaf-like structures on top of the fruit a trait that was selected for thousands of years ago, in the early days of tomato domestication. The benefits of this trait are unclear, Lippman says, but it may have helped to support heavier fruits.

With these genes uncovered, his team used CRISPRCas9 editing to eliminate their activity, as well as that of a third gene that also affects flower number, in various combinations. This generated a range of plant architectures, from long, spindly flower-bearing branches to bushy, cauliflower-like bunches of flowers including some with improved yields.

The findings should help to quell lingering doubts among plant breeders that negative interactions between desirable genetic traits are a force to be reckoned with, says Andrew Paterson, a plant breeder at the University of Georgia in Athens. The idea has been controversial, he says, because the effects have been difficult to detect statistically.

Lippmans team is now working with plant breeders to use gene editing to develop tomatoes with branches and flowers optimized for the size of the fruit. Plants with larger fruit, for example, may have better yields if they have fewer flowering branches than those with smaller fruit.

We really are tapping into basic knowledge and applying it to agriculture, he says. And ironically, it happens to be in the crop that I least liked harvesting on the farm.

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Fixing the tomato: CRISPR edits correct plant-breeding snafu - Nature.com

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May 18, 2017 by Gary Finnegan, From Horizon Researchers in Norwich, UK, are hoping to make crops more resistant to disease. Credit: Kamoun Lab @ TSL

As the world's population rises, scientists want to edit the genes of potatoes and wheat to help them fight plant diseases that cause famine.

By 2040, there will be 9 billion people in the world. "That's like adding another China onto today's global population," said Professor Sophien Kamoun of the Sainsbury Laboratory in Norwich, UK.

Prof. Kamoun is one of a growing number of food scientists trying to figure out how to feed the world. As an expert in plant pathogens such as Phytophthora infestans the fungus-like microbe responsible for potato blight he wants to make crops more resistant to disease.

Potato blight sparked the Irish famine in the 19th century, causing a million people to starve to death and another million migrants to flee. European farmers now keep the fungus in check by using pesticides. However, in regions without access to chemical sprays, it continues to wipe out enough potatoes to feed hundreds of millions of people every year.

"Potato blight is still a problem," said Prof. Kamoun. "In Europe, we use 12 chemical sprays per season to manage the pathogen that causes blight, but other parts of the world cannot afford this."

Plants try to fight off the pathogens that cause disease but these are continuously changing to evade detection by the plant's immune system.

Arms race

In nature, every time a plant gets a little better at fighting off infection, pathogens adapt to evade their defences. Now biologists are getting involved in the fight.

"It's essentially an arms race between plants and pathogens," said Prof. Kamoun. "We want to turn it into an arms race between biotechnologists and pathogens by generating new defences in the lab."

Five years ago, Prof. Kamoun embarked on a project called NGRB, funded by the EU's European Research Council. The plan was to find a way to make potatoes more resistant to infection using advanced plant-breeding techniques.

Then serendipity struck. In the early stages of the project, scientists in another lab discovered a ground-breaking gene-editing technique known as CRISPR-Cas which allows scientists to delete or add genes at will. As well as having potential medical applications in humans, this powerful tool is unlocking new approaches to perfecting plants.

"If we think of the genome as text, CRISPR is a word processor that allows us to change just a letter or two," explained Prof. Kamoun. "The precision that this allows makes CRISPR the ultimate in genetic editing. It's really beautiful."

One of the simplest ways to use CRISPR to improve plants is to remove a gene that makes them vulnerable to infection. This alone can make potatoes more resilient, helping to meet the world's growing demand for food.

The resulting crop looks and tastes just the same as any other potato. Prof. Kamoun says that potatoes which are missing a gene or two should not be viewed in the same way as genetically modified foods which sometimes contain genes introduced from another species. "It's a very important technical difference but not all regulators have updated their rules to make this distinction."

Potatoes are not the only food crops that can be improved by CRISPR-Cas. Prof. Kamoun is now working on a project that aims to protect wheat from wheat blast a fungal disease decimating yields in Bangladesh and spreading in Asia.

Looking ahead, CRISPR will be used to improve the quality and nutritional value of wheat, rice, potatoes and vegetables. It could even be used to remove genes that cause allergic reactions in people with tomato or wheat intolerance.

"If we can remove allergens, consumers may soon see hypoallergenic tomatoes on supermarket shelves," Prof. Kamoun said. "It's a very exciting technology."

While targeting disease in this way could be a game changer for global food security in the years ahead, experts believe other approaches to plant breeding will continue to have a role. Understanding meiosis a type of cell division that can reshuffle genes to improve plants can help farmers and the agribusiness sector select for hardier crops, according to Professor Chris Franklin of the University of Birmingham, UK.

He leads the COMREC project, which trains young scientists to understand and manipulate meiosis in plants. The project applies the wealth of knowledge generated by leaders in the field to tackle the pressing problem of feeding a hungry world.

"COMREC has begun to translate fundamental research into (applications in) key crop species such as cereals, brassicas and tomato," said Prof. Franklin. "Close links with plant-breeding companies have provided important insight into the specific challenges confronted by the breeders."

Elite crops

There may be untapped potential in this approach to plant breeding: most of the genes naturally reshuffled during meiosis in cereal crops are at the far ends of chromosomes genes in the middle of chromosomes are rarely reshuffled, limiting the scope for new crop variations.

COMREC's academic and industry partners hope to understand why this is so that they can find a way to shuffle the genes in the middle of chromosomes too. And the food industry is keen to produce new 'elite varieties' that are better adapted to confront the challenges arising from climate change, says Prof. Franklin.

"A number of genes have now been identified that can make this reshuffling relatively more frequent," he said. "CRISPR-Cas provides a way to modify the corresponding genes in crop species, helping to translate this basic research to target crops."

Explore further: US approves 3 types of genetically engineered potatoes (Update)

More information: Targeted mutagenesis in the model plant Nicotiana benthamiana using Cas9 RNA-guided endonuclease by Vladimir Nekrasov, Brian Staskawicz, Detlef Weigel, Jonathan D G Jones & Sophien Kamoun in Nature Biotechnology 31, 691693 (2013). DOI: 10.1038/nbt.2655

Involvement of the Cohesin Cofactor PDS5 (SPO76) During Meiosis and DNA Repair in Arabidopsis thaliana by Mnica Pradillo, Alexander Knoll, Cecilia Oliver, Javier Varas, Eduardo Corredor, Holger Puchta and Juan L. Santos in Front. Plant Sci., 01 December 2015 . DOI: 10.3389/fpls.2015.01034

Three types of potatoes genetically engineered to resist the pathogen that caused the Irish potato famine are safe for the environment and safe to eat, federal officials have announced.

Scientists on Monday said they have found a gene to help protect potatoes from a blight that unleashed a devastating famine in Ireland in the 19th century.

Growing crops with stacks of two or more resistance genes from closely related species, introduced into the crop via for instance genetic engineering, combined with the simultaneous introduction of resistance management, ...

A team of scientists from The Sainsbury Laboratory (TSL) and The Genome Analysis Centre (TGAC) have developed a new method to accelerate isolation of plant disease resistance genes. The team have also identified a brand new ...

When you pick up the perfect apple in the supermarket it's easy to forget that plants get sick just like we do. A more realistic view might come from a walk outside during summer: try to find a leaf without a speck, spot ...

We all know that animals have an immune system - but plants have systems to fight infection too. Plant cells have receptor proteins which bind with parts of a pathogen. These receptor proteins are located on the surface of ...

(Phys.org)A pair of researchers from Stanford University has studied the energy used by a type of small parrot as it hops from branch to branch during foraging. As they note in their paper uploaded to the open access site ...

A new Oxford University collaboration revealing the world's prime insect predation hotspots, achieved its landmark findings using an unusual aid: plasticine 'dummy caterpillars.'

Breeding in plants and animals typically involves straightforward addition. As beneficial new traits are discoveredlike resistance to drought or larger fruitsthey are added to existing prized varieties, delivered via ...

After decades of research aiming to understand how DNA is organized in human cells, scientists at the Gladstone Institutes have shed new light on this mysterious field by discovering how a key protein helps control gene organization.

Researchers have successfully developed a novel method that allows for increased disease resistance in rice without decreasing yield. A team at Duke University, working in collaboration with scientists at Huazhong Agricultural ...

University of Chicago psychology professor Leslie Kay and her research group set out to resolve a 15-year-old scientific dispute about how rats process odors. What they found not only settles that argument, it suggests an ...

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Can CRISPR feed the world? - Phys.org - Phys.Org

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By Robert F. ServiceMay. 17, 2017 , 2:30 PM

It takes more than a cast and a little time to heal many broken bones. Whether its a soldier wounded in battle, a car accident victim, or an elderly person who has fallen, bone damage can be so extensive that the bones never heal properly, leaving people crippled or with other severe problems. Now, researchers have combined ultrasound, stem cells, and gene therapy to stimulate robust bone repair. So far the work has only been performed in animals. But it has already been so successful that its expected to move quickly toward human clinical trials.

The new research has huge clinical significance, says David Kulber, who directs the Center for Plastic and Reconstructive Surgery at Cedars-Sinai Medical Center in Los Angeles, California, and who was not part of the study. The technology of being able to stimulate bone growth is really remarkable.

Its also one for which there is a glaring need. In the United States alone, some 100,000 people a year suffer from what is known as a nonunion fracture. In these cases, parts of a bone may be missing altogether or so badly splintered that the bone cant be reassembled. In such cases, doctors typically graft other bone into the site. Ideally this bone comes from the same personoften taken from the pelvis, a painful procedure that compounds a persons injuries and recovery time. When this isnt possible, physicians will turn to cadavers for the extra bone. But this bone must be sterilized before its implanted, robbing it of proteins and other signaling molecules that encourage its regrowth once transplanted, and lessening the chances of a full recovery.

Researchers have long tried to improve matters by growing new bone without use of a graft. To do so they typically first fill gaps in bone with a natural scaffolding material called collagen. This scaffolding encourages a persons own bone-forming stem cells, called mesenchymal stem cells (MSCs), to migrate into the area. The trouble is MSCs dont only differentiate into osteocytes, the bone-producing cells. They can also develop into either fat tissue cells or scar tissue.

Researchers have tried for years to steer MSCs into becoming osteocytes by exposing them to one or more bone morphogenetic proteins (BMPs), signaling molecules that trigger the cells to transform into bone-forming cells. But for this differentiation to occur, MSCs must be exposed to BMPs for up to a week. Yet if the BMPs are simply injected into the site of a fracture, they dissipate in just hours.

In an effort to produce a lasting BMP signal, researchers led by Dan Gazit, a regenerative medicine expert at Cedars-Sinai, as well as other groups, have previously turned to using viruses to introduce extra copies of BMP genes into MSCs so that the cells themselves will produce the proteins long enough to trigger their own differentiation. But success has been halting here, too.

Over the last several years, Gazits teamamong othershasdeveloped an alternative strategy for efficiently getting genes into MSCs without viruses. The researchers start by packing the wound with the usual collagen matrix and waiting for a couple of weeks for the stem cells to infiltrate the scaffold. They then create a solution containing numerous copies of their gene of interest alongside gas-filled micron-sized bubbles encased by a thin shell of fat molecules. After injecting this solution into the fracture site, they go over the area with an ultrasound wand, much as its done by obstetricians to check on the health of a fetus. The wands ultrasound pulses burst the microbubbles, briefly punching nano-sized holes in any adjacent stem cells, which allows the genes in the solution to enter.

In 2014, Gazit and his colleagues reported that they used this procedure to introduce nontherapeutic reporter genes into large fractures in animal models. But when they used the procedure to introduce genes for two different BMPsBMP-2 and BMP-7they detected some bone regrowth in the animals, but not enough to heal the fractures.

Gazits group has gotten better results by using the same approach to insert copies of the gene for BMP-6 into pigs that had been surgically given 1-centimeter gaps in a leg bone. After waiting 8 weeks, they found that the bone gap was closed and the leg fracture was healed in all of the treated animals. In fact, the procedure was so effective that the fractures healed as well as when bone grafts were carried out using bone from the same animal, the currently preferred treatment, they report today in Science Translational Medicine.

The results are just the type of thing we need to move this field forward, says Johnny Huard, an orthopedics researcher at the University of Texas Health Science Center in Houston. However, he notes, the pigs used in this study were all under 1 year in age. Younger animals, including people, tend to have far more MSCs than older ones, he says, yet large fractures are far more common in the elderly than the young. So Huard suggests that before the approach is ready for testing in people with bone fractures, it would be good to first see whether its equally successful in older animals.

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Tiny bubbles and a bit of gene therapy heal major bone fractures in pigs - Science Magazine

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Press Release: New Stem Cell Collection Center Opens in Boston The Scientist We support biomedical researchers globally by offering human hematopoietic stem cells and blood derived cell products from bone marrow, cord blood, peripheral blood and mobilized peripheral blood. StemExpress guarantees every sample delivers only ...

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Press Release: New Stem Cell Collection Center Opens in Boston - The Scientist

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