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Dogs Wanted for Massive Study on Aging in Canines – The Bark

February 27th, 2020 8:42 pm

Almost 80,000 dogs have been nominated to participate in a new nationwide study on dog aging since registration began last fall, but theres still time for your dog to become part of the pack.

We know from previous work done with dog owners that they are motivated to help their dogs live longer, healthier lives, but the response has been positively overwhelming, saidAudrey Ruple, a veterinary epidemiologist and assistant professor of One Health Epidemiology in the Purdue UniversityCollege of Health and Human SciencesDepartment of Public Health.

TheDog Aging Projectwill look at dogs from all breeds and mixes from across the nation. This is the first major longitudinal study involving dogs, and it's scheduled to last at least 10 years.

Dogs are good models for humans, said Ruple, who is one of more than 40 scientists and researchers participating in the study. They have similar genetics, share our environment, and they also have similar diseases and health issues. We will be asking, How do dogs age healthfully? in order to help better understand how we can age healthfully, too.

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Dogs of all age ranges, breeds and sizes are eligible to participate. Owners can goonlinefor more information and to register their dogs. The most popular breeds submitted so far for the study are Labrador retriever, golden retriever, German shepherd, dachshund, Australian shepherd, poodle, chihuahua, shih tzu, boxer and Yorkshire terrier.

Once enrolled, owners will need to complete surveys about their dogs health and lifestyle.Dogs must go through their regular annual examination with their veterinarian. If a dog is assigned to a specific study group, owners may be sent a kit for the veterinarian to collect blood, urine or other samples during the annual visit. Participation is voluntary, and there is no cost to participate.

Ruple said the group also is trying to find the nation's oldest dog.

Dogs have been nominated from all 50 states. The states with the most nominated canines are California, Washington, Texas, Florida, New York, Illinois, Pennsylvania, North Carolina, Colorado and Ohio. States with the least nominations are North Dakota, South Dakota, Wyoming, Delaware and Mississippi.

The group has had nine dogs nominated that were 24 years old, as well as nine other dogs that were 23 years old.

All dogs registered will be eligible to participate in various studies.

Researchers hope to find out more details on how factors like an individuals genome, proteome, microbiome, demographics and environmental factors such as chemical exposures and noise pollution impact health and longevity.

Ruple said one goal of the study is to not just improve the health and longevity of dogs, but also extend those findings to improve human health.

By studying aging in dogs, we hope to learn how to better match human health span to life span so that we can all live longer, healthier lives, Ruple said.

Funding for the Dog Aging Project comes from the National Institute of Aging, a part of the National Institutes of Health, as well as from private donations.

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Dogs Wanted for Massive Study on Aging in Canines - The Bark

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Car T-cell therapy: The future fifth pillar of cancer treatment – The Irish Times

February 27th, 2020 8:41 pm

Revolutionary Car T-cell therapy is set to become the fifth pillar of cancer treatment and is already showing dramatic results in the successful treatment of blood cancers.

Prof Owen Smith is a consultant paediatric haematologist who has dedicated his 35-year career to researching and treating cancer in children and young adolescents. Smith, who is based at Childrens Health Ireland at Crumlin hospital, is a specialist in stem cell transplantation. Over the years, he has seen big advances in cancer treatments but few have excited him as much as Car T-cell therapy which is showing huge potential as a pioneering treatment for blood and other challenging cancers.

In a nutshell, Car (chimeric antigen receptor) T-cell therapy is a form of immunotherapy that uses the patients own immune cells to recognise and attack cancer. It involves drawing blood from the patient, isolating the T-cells within it and genetically altering and multiplying them in a lab. The end product is transfused back into the patient where the Car T-cells bind to an antigen or structural molecule on the cancer cells and kills them.

Car T-cells or Cars for short, are like sniper fire that target the cancer rather than blanket bombing it, explains Prof Smith. They cause much less toxicity than chemotherapy and have much better results and remission rates.

Cars therapy has been in gestation since the early 1980s with the first-generation treatment becoming available around 2010.

To date, about 2,200 Cars have been completed in the US, while in Europe the number is about 800 and growing fast. There are now two second generation Car T products licensed for three types of blood cancer and Prof Smith says: We now have hope with these relapse/refractory blood cancers where only a few years ago, we had none.

Prof Smith was working in Royal Free Hospital in London (one of the UKs major Car T therapy centres today) in the 1980s when the therapeutic potential of T-cells, which was initially discovered in Israel, was first being realised. It became clear through some good connected thinking that it was the T-cells that were having a very important effect on cure in patients with CML (chronic myeloid leukaemia), he says. Around the same time there were papers coming in from the States with similar results so the concept was beginning to gather momentum.

The question became: could you take T-cells from a donor and give them to people who were relapsing and put them into remission? Things began to crystallise in the late 80s/early 90s as T cells were recognised as immune effector cells that were very good at killing cancer, especially in patients with CML who were relapsing after stem cell transplantation.

Then people began wondering if we could use the end of the molecule the so-called antigen binding part of an antibody and link it to the T-cell receptor and put it into T-cells to see if that would give an even better result. What eventually followed between 2010 and 2014 were a number of first generation Car T-cell studies that showed it was very effective in some patients with haematological malignancies and in those with acute lymphoblastic and chronic lymphocytic leukaemia in particular. Since then there have been 10 big studies with second generation Cars that have also proved its efficacy, says Prof Smith.

Acute lymphoblastic leukaemia is the most common form of blood cancer in children and Prof Smith sees about 50 cases a year here. Unfortunately, if this cancer relapses, particularly during or shortly after chemotherapy, it usually becomes resistant to further treatment and the children can also no longer tolerate it. The only option up to now has been palliative care, but Cars is a lifeline that can alter this outcome.

Second generation Car T-cell activity can push around 90 per cent of children into remission and once you get them into remission you have time to get them into prime clinical condition to give them a stem cell transplant and cure them that way, says Prof Smith. In the adult population, about 20 cases a year of non-Hodgkins lymphoma would be suitable for this therapy.

Weve known for a long time that the immune system is important in someone developing cancer, Prof Smith adds. So, for example when a persons T-cells are knocked out by something like HIV, they typically have an increased risk of developing lymphoid malignancies. The immune system can also be tricked into not recognising when a cancer develops and undergoes metastatic spread. This immune activation therapy can unmask this camouflaging of the cancer resulting in regression.

One of the challenges with the Cars is that they can become lost in the body and lose their persistence. When this happens the person usually relapses. We are now looking at different combinations of Cars and using two or three of them on the one cell to prevent relapse, says Prof Smith.

This is a massively evolving field and one of these exponential technologies you hear about from time to time. Whats really encouraging it that its now being pushed out to treat other types of high-risk solid tumours that currently have dismal survival rates such as metastatic non-small cell lung cancer, pancreatic cancer, triple negative breast cancer, ovarian cancer, brain tumours and neuroblastomas in children. Its opening up a totally different treatment pathway for cancer.

Prof Smith acknowledges that Cars, like many innovative cancer treatments, is expensive at about 300,000 per commercially produced treatment. But he points out that as its use becomes more widespread prices will drop and that if the total costs of conventional treatments are added up the economic argument for its use is compelling. Yes, its costly but some recent health economic data from the USA is suggesting it may not be as costly as it first appears, he says. Specifically, repeated chemotherapy, the cost of regular hospital admissions due to relapse, trips to intensive care, blood product support and anti-bacterial, anti-fungal and anti-viral therapies all with very little return in terms of clinical outcome.

Prof Smith adds that Car T therapy is set to become the fifth pillar of cancer treatment alongside surgery, chemotherapy, radiation and targeted therapy and that whats happening now is just the start of the Car T revolution. The next phase will be using them in combination with checkpoint inhibitors (another arm of immunotherapy) and the third generation of Cars will have greater efficacy and less toxicity, he says.

Prof Smith is low key about his personal achievements but in addition to saving the lives of countless children under his care, he also has a distinguished research record and his work has been widely published and acknowledged internationally. He was to the forefront of a major breakthrough in the intervention and treatment of meningitis in the 1980s and he is a strong believer in robust peer-reviewed clinical trials, which he believes are one of the most effective ways of establishing a cure for any disease.

Owen Smith is professor of Paediatric and Adolescent Medicine at UCD, honorary Regius Professor of Physic (1637) at Trinity College and academic lead to the Childrens Hospital Group. He is also a principal investigator at the National Childrens Research Centre and Systems Biology Ireland at University College Dublin and national clinical programme lead for children and adolescents/young adults with cancer. In 2015 he was awarded a CBE by Queen Elizabeth for his life-long dedication to treating cancer in children.

Prof Smith is a speaker at the international BioPharma Ambition 2020 event which is being held in Dublin Castle on March 3rd and 4th.

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Policy and public health: all the decisions we can’t see – PMLiVE

February 27th, 2020 8:41 pm

Lets be honest, January was a bad month for healthcare news coming out of China.

For starters, at the end of December, a Chinese court sentenced He Jiankui to three years in prison for operating an illegal medical practice, which includes using a fake ethical review certificate and misleading participants about a studys risks, and also violating an ethics guidance from 2003 that barred the reproductive use of research embryos.

You may remember Dr Jiankui as the individual who made the worlds first genetically edited babies by recruiting couples in which the man was HIV positive but the woman was not, as part of an effort to create embryos with a genetic mutation that made the couples offspring protected from the virus.

Esteemed bioethicists and scholars, such as Josephine Johnston from the Hastings Center that produces books, articles and other publications on ethical questions in medicine, science and technology that help inform policy, practice and public understanding, as well as Robin Lovell-Badge, a stem cell biologist at the Francis Crick Institute, have both acknowledged that He Jiankuis work straddled a line that might have got them in hot water in both the US and the UK.

In fact, Lovell-Badge said in a statement distributed by the United Kingdoms Science Media Centre that both prison and a fine would have been the likely penalties if someone had done what [He Jiankui] did in the UK.

And then, in early January, China informed the world about a deadly new coronavirus that has been causing severe respiratory illness and death among its citizens.

As of 6 February, in China there were over 28,000 confirmed cases and 565 people have died there; in addition there were more than 220 confirmed cases outside China and there has been one death in the Philippines.

On 26 January, the New York Times wrote: The outbreak has drawn fresh attention to Chinas animal markets, where the sale of exotic wildlife has been linked to epidemiological risks. The Wuhan virus is believed to have spread from one such market in the city. The SARS outbreak nearly two decades ago was also traced back to the wildlife trade.

These two scenarios highlight an important aspect of public health and health policy: complex decisions that require almost real-time response are only as good as the information upon which those decisions are based.

In the case of He Jiankui, many countries have policies and laws in place against germline gene editing. But because the court proceedings, documentation and testimony in this case have not been made public, it is impossible to know the details surrounding the events that may have facilitated this rogue scientists behaviour.

And because we dont have those details, implementing new health policy to prevent recurrences of this situation remains difficult. Not impossible, but difficult. Some will argue that US and UK laws are expansive enough and the penalties imposing enough on their own merits that we need not fret about a single scientists actions in a universally agreed upon opaque scientific ecosystem.

Others will argue that the scientific communitys overwhelmingly negative response and outrage will discourage this from happening again. I disagree.

And in the coronavirus situation, the same New York Times article went on to say: Conclusive evidence about how this outbreak started is lacking. Although officials in Wuhan first traced it to a seafood market, some who have fallen ill never visited the market.

'Researchers have also offered disparate explanations about which animals may have transmitted the virus to humans. Chinas record doesnt help. During the SARS epidemic in 2002 and 2003, officials covered up the extent of the crisis, delaying the response. The Chinese government has promised far more transparency this time, and the World Health Organization (WHO) has praised its cooperation with scientists.

Im sure we all feel better that a non-partisan agency like the WHO has authenticated the cooperation of the Chinese scientific community in 2020 but the issue is far more complex.

We need to understand the larger social and cultural issues that may be driving the underlying causes of these deadly illnesses. And in order to do that, the Chinese governments openness to the rest of the worlds questions and, ultimately, its willingness to revise public policy to reflect a greater harmonisation for global public health will be put to the test.

This is not a China issue. Its a transparency issue. Whether its the reporting of a measles outbreak in America or the promulgationof information on Ebola cases in West Africa, we are all responsible because the world needs more transparency.

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Kadmon Announces Expanded Results of Interim Analysis of Pivotal Trial of KD025 in cGVHD – Yahoo Finance

February 27th, 2020 8:41 pm

Patient Analyses and Safety Data Continue to Underscore Positive Impact of KD025 in cGVHD

Pre-NDA Meeting with FDA Planned for March 2020; Topline Results of Primary Analysis to be Announced in Q2 2020

NEW YORK, NY / ACCESSWIRE / February 23, 2020 / Kadmon Holdings, Inc. (KDMN) today announced expanded results from the previously reported interim analysis of ROCKstar (KD025-213), its ongoing pivotal trial of KD025 in chronic graft-versus-host disease (cGVHD). The data were presented today in the oral latebreaker session at the 2020 Transplantation & Cellular Therapy (TCT) Meetings.

As announced in November 2019, KD025 met the primary endpoint of Overall Response Rate (ORR) at the study's planned interim analysis, two months after completion of enrollment. KD025 showed statistically significant and clinically meaningful ORRs of 64% with KD025 200 mg once daily (95% Confidence Interval (CI): 51%, 75%; p<0.0001) and 67% with KD025 200 mg twice daily (95% CI: 54%, 78%; p<0.0001). In the expanded KD025-213 dataset presented today, ORRs were consistent with the previously reported interim analysis across key subgroups, including in patients with four or more organs affected by cGVHD (n=69; 64%), patients who had prior treatment with ibrutinib (n=45; 62%) and patients who had prior treatment with ruxolitinib (n=37; 62%). Three patients achieved a Complete Response. Responses were observed in all affected organ systems, including in organs with fibrotic disease. KD025 has been well tolerated: adverse events were consistent overall with those expected to be observed in cGVHD patients receiving corticosteroids, and no apparent increased risk of infection was observed. Additional secondary endpoints, including duration of response, corticosteroid dose reductions, Failure-Free Survival, Overall Survival and Lee Symptom Scale reductions continue to mature and will be available later in 2020.

"KD025 has been well tolerated and has already demonstrated high response rates in patients with severe and complex cGVHD after a median of five months of follow-up," said Corey Cutler, MD, MPH, FRCPC, Associate Professor of Medicine, Harvard Medical School; Medical Director, Adult Stem Cell Transplantation Program, Dana-Farber Cancer Institute and a KD025-213 study investigator and Steering Committee member.

"We are extremely pleased with the interim outcomes of this pivotal trial of KD025 in cGVHD, which track closely our findings from our earlier Phase 2 study. KD025 achieved robust response rates across all subgroups of this difficult-to-treat patient population, who had a median of four prior lines of therapy, and 73% of whom had no response to their last line of treatment," said Harlan W. Waksal, M.D., President and CEO of Kadmon. "We plan to meet with the FDA for a pre-NDA meeting in March 2020 and to announce topline results from the primary analysis of this trial in Q2 2020."

At the TCT Meetings, Kadmon also presented long-term follow-up data from KD025-208, its ongoing Phase 2 study of KD025 in cGVHD (Abstract #15205). These data were recently presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in December 2019.

About the ROCKstar (KD025-213) Trial

KD025-213 is an ongoing open-label trial of KD025 in adults and adolescents with cGVHD who have received at least two prior lines of systemic therapy. Patients were randomized to receive KD025 200 mg once daily or KD025 200 mg twice daily, enrolling 66 patients per arm. Statistical significance is achieved if the lower bound of the 95% CI of ORR exceeds 30%.

While the ORR endpoint was met at the interim analysis, which was conducted as scheduled two months after completion of enrollment, topline data from the primary analysis of the KD025-213 study, six months after completion of enrollment, will be reported in Q2 2020. Full data from the primary analysis will be submitted for presentation at an upcoming scientific meeting.

About KD025

KD025 is a selective oral inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2), a signaling pathway that modulates immune response as well as fibrotic pathways. In addition to cGVHD, KD025 is being studied in an ongoing Phase 2 clinical trial in adults with diffuse cutaneous systemic sclerosis (KD025-209). KD025 was granted Breakthrough Therapy Designation and Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of patients with cGVHD who have received at least two prior lines of systemic therapy.

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About cGVHD

cGVHD is a common and often fatal complication following hematopoietic stem cell transplantation. In cGVHD, transplanted immune cells (graft) attack the patient's cells (host), leading to inflammation and fibrosis in multiple tissues, including skin, mouth, eye, joints, liver, lung, esophagus and gastrointestinal tract. Approximately 14,000 patients in the United States are currently living with cGVHD, and approximately 5,000 new patients are diagnosed with cGVHD per year.

About Kadmon

Kadmon is a clinical-stage biopharmaceutical company that discovers, develops and delivers transformative therapies for unmet medical needs. Our clinical pipeline includes treatments for immune and fibrotic diseases as well as immuno-oncology therapies.

Forward Looking Statements

This press release contains forward-looking statements. Such statements may be preceded by the words "may," "will," "should," "expects," "plans," "anticipates," "could," "intends," "targets," "projects," "contemplates," "believes," "estimates," "predicts," "potential" or "continue" or the negative of these terms or other similar expressions. Forward-looking statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. We believe that these factors include, but are not limited to, (i) the initiation, timing, progress and results of our preclinical studies and clinical trials, and our research and development programs; (ii) our ability to advance product candidates into, and successfully complete, clinical trials; (iii) our reliance on the success of our product candidates; (iv) the timing or likelihood of regulatory filings and approvals; (v) our ability to expand our sales and marketing capabilities; (vi) the commercialization of our product candidates, if approved; (vii) the pricing and reimbursement of our product candidates, if approved; (viii) the implementation of our business model, strategic plans for our business, product candidates and technology; (ix) the scope of protection we are able to establish and maintain for intellectual property rights covering our product candidates and technology; (x) our ability to operate our business without infringing the intellectual property rights and proprietary technology of third parties; (xi) costs associated with defending intellectual property infringement, product liability and other claims; (xii) regulatory developments in the United States, Europe, China, Japan and other jurisdictions; (xiii) estimates of our expenses, future revenues, capital requirements and our needs for additional financing; (xiv) the potential benefits of strategic collaboration agreements and our ability to enter into strategic arrangements; (xv) our ability to maintain and establish collaborations or obtain additional grant funding; (xvi) the rate and degree of market acceptance of our product candidates; (xvii) developments relating to our competitors and our industry, including competing therapies; (xviii) our ability to effectively manage our anticipated growth; (xix) our ability to attract and retain qualified employees and key personnel (xx) the potential benefits from any of our product candidates being granted orphan drug or breakthrough designation; (xxi) the future trading price of the shares of our common stock and impact of securities analysts' reports on these prices; and/or (xxii) other risks and uncertainties. More detailed information about Kadmon and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's filings with the U.S. Securities and Exchange Commission (the "SEC"), including the Company's Annual Report on Form 10-K for the fiscal year ended December 31, 2018 and subsequent Quarterly Reports on Form 10-Q. Investors and security holders are urged to read these documents free of charge on the SEC's website at http://www.sec.gov. The Company assumes no obligation to publicly update or revise its forward-looking statements as a result of new information, future events or otherwise.

Contact Information

Ellen Cavaleri, Investor Relations646.490.2989ellen.cavaleri@kadmon.com

SOURCE: Kadmon Holdings, Inc.

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Global Synthetic (Cultured) Meat Market : Full In-depth Analysis by Top Key Players, Regional Outlook, Latest Trend and Forecast to 2024 – Nyse Nasdaq…

February 26th, 2020 8:47 pm

The Synthetic (Cultured) Meat report delineates the key features rendering the growth of the global Synthetic (Cultured) Meat Market. The research study is a prolific account of macroeconomic and microeconomic factors boosting the growth of the global Synthetic (Cultured) Meat market. It also exhibits the market valuation within the calculated time period, thereby helping market players to make appropriate changes in their approach towards attaining growth and sustaining their position in the industry.

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Synthetic (Cultured) Meat market competition by top Manufacturers: Aleph Farms, Finless Foods, Future Meat Technologies, Integriculture Inc., JUST Inc., SuperMeat, Appleton Meats, Avant Meats Company Limited, Balletic Foods, Biofood Systems LTD., Bluenalu, Inc., Cell Farm FOOD Tech/Granja Celular S.A.

By the product type, the market is primarily split into: Soy Protein Type, Animal Stem Cell Synthesis Type, Others

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What’s coming down the pike in the dental profession? – Dentistry IQ

February 26th, 2020 8:45 pm

Maryp | Dreamstime.com

A plethora of dental research is underway in the US as well as globally. Some of these advancements will come to fruition and be commercially available, and some will die on the vine. There are innovations in essentially every dental discipline, with breakthroughs that have the potential to enhance oral health in ways we couldnt imagine in the past.

The impact of artificial intelligence (AI) will increase in the future. AI is already at work in hospitals to diagnose cancer and anticipate trends in health care. AI will have a significant effect in the dental profession on a daily basis, from evaluating images for pathology, to prosthetics and systemic care, among many others. AI promises to increase efficiency in dental practice by facilitating faster diagnosis, predictive analytics, and autocharting.

Other areas of research and development include gene therapy and stem cells. Research is underway using gene therapy to restore salivary function in patients who have undergone radiation treatment, which could be a tremendous improvement in health for these individuals. The negative impact of dry mouth extends far beyond the discomfort associated with inadequate or complete lack of saliva. It has a significant effect on the quality of life of the individual and the health of the oral cavity. The ability to restore salivary function could be life-changing for many people.

Other initiatives involve transformative research in periodontics, specifically agents operating on the host response and others applied to the diseased periodontal pockets. Some of the research on host-response therapies involves agents that repair the immune system dysfunction responsible for tissue degeneration. This is accomplished by using minute quantities of an agent that creates a gradient, resulting in the mobilization of regulatory cells that dampen down the inflammatory response, which is responsible for the tissue destruction that accompanies periodontal disease.

Some of the research focused on the clinical application of agents into periodontal pockets does not involve antimicrobial therapies, but rather are regenerative in nature. Preparation of the affected area is simple and quick, followed by application of the regenerative agent. Clinical trials have demonstrated significant pocket depth reduction and bone regeneration. If these results are consistent and reproducible, a complete paradigm shift in the treatment of periodontitis could occurone that is essentially noninvasive, quick, and inexpensive.

There are a number of disruptive technologies in various stages of development that will dramatically change the manner in which we practice dentistry. Some of these changes will mirror developments in the medical profession, such as gene therapy and influencing the immunoinflammatory system to reduce tissue damage, which ultimately benefits the individuals oral and overall health.

Editor's note: Would you like to learn more about the latest in oral-systemic research?Write to Dr. Richard Nagelbergabout topics youve read about in this blog or submit items youd like to see covered here.

Previous blog: Updates on periodontal disease pathogens and the heart

Editor's note: This article originally appeared in Breakthrough Clinical, aclinical specialties newsletter from Dental Economics and DentistryIQ. Read more articles at this link.

Richard H. Nagelberg, DDS, has practiced general dentistry in suburban Philadelphia for more than 30 years. He is a speaker, advisory board member, consultant, and key opinion leader for several dental companies and organizations. He lectures on a variety of topics centered on understanding the impact dental professionals have beyond the oral cavity. Contact Dr. Nagelberg atrnagelberg@orapharma.com.

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On the Road to 3-D Printed Organs – The Scientist

February 26th, 2020 8:45 pm

For years, scientists have predicted that 3-D printingwhich has been used it to make toys, homes, scientific tools and even a plastic bunny that contained a DNA code for its own replicationcould one day be harnessed to print live, human body parts to mitigate a shortage of donor organs. So far, researchers also used 3-D printing in medicine and dentistry to create dental implants, prosthetics, and models for surgeons to practice on before they make cuts on a patient. But many researchers have moved beyond printing with plastics and metalsprinting with cells that then form living human tissues.

No one has printed fully functional, transplantable human organs just yet, but scientists are getting closer, making pieces of tissue that can be used to test drugs and designing methods to overcome the challenges of recreating the bodys complex biology.

A confocal microscopy image showing 3-Dprinted stem cells differentiating into bone cells

The first 3-D printer was developed in the late 1980s. It could print small objects designed using computer-aided design (CAD) software. A design would be virtually sliced into layers only three-thousandths of a millimeter thick. Then, the printer would piece that design into the complete product.

There were two main strategies a printer might use to lay down the pattern: it could extrude a paste through a very fine tip, printing the design starting with the bottom layer and working upward with each layer being supported by the previous layers. Alternatively, it could start with a container filled with resin and use a pointed laser to solidify portions of that resin to create a solid object from the top down, which would be lifted and removed from the surrounding resin.

When it comes to printing cells and biomaterials to make replicas of body parts and organs, these same two strategies apply, but the ability to work with biological materials in this way has required input from cell biologists, engineers, developmental biologists, materials scientists, and others.

So far, scientists have printed mini organoids and microfluidics models of tissues, also known as organs on chips. Both have yielded practical and theoretical insights into the function of the human body. Some of these models are used by pharmaceutical companies to test drugs before moving on to animal studies and eventually clinical trials. One group, for example, printed cardiac cells on a chip and connected it to a bioreactor before using it to test the cardiac toxicity of a well-known cancer drug, doxorubicin. The team showed that the cells beating rate decreased dramatically after exposure to the drug.

However, scientists have yet to construct organs that truly replicate the myriad structural characteristics and functions of human tissues. There are a number of companies who are attempting to do things like 3-D print ears, and researchers have already reported transplanting 3-D printed ears onto children who had birth defects that left their ears underdeveloped, notes Robby Bowles, a bioengineer at the University of Utah. The ear transplants are, he says, kind of the first proof of concept of 3-D printing for medicine.

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Bowles adds that researchers are still a ways away from printing more-complex tissues and organs that can be transplanted into living organisms. But, for many scientists, thats precisely the goal. As of February 2020, more than 112,000 people in the US are waiting for an organ transplant, according to the United Network for Organ Sharing. About 20 of them die each day.

For many years, biological engineers have tried to build 3-D scaffolds that they could seed with stem cells that would eventually differentiate and grow into the shapes of organs, but to a large extent those techniques dont allow you to introduce kind of the organization of gradients and the patterning that is in the tissue, says Bowles. There is no control over where the cells go in that tissue. By contrast, 3-D printing enables researchers with to very precisely direct the placement of cellsa feat that could lead to better control over organ development.

Ideally, 3-D printed organs would be built from cells that a patients immune system could recognize as its own, to avoid immune rejection and the need for patients to take immunosuppressive drugs. Such organs could potentially be built from patient-specific induced pluripotent stem cells, but one challenge is getting the cells to differentiate into the subtype of mature cell thats needed to build a particular organ. The difficulty is kind of coming together and producing complex patternings of cells and biomaterials together to produce different functions of the different tissues and organs, says Bowles.

To imitate the patterns seen in vivo, scientists print cells into hydrogels or other environments with molecular signals and gradients designed to coax the cells into organizing themselves into lifelike organs. Scientists can use 3-D printing to build these hydrogels as well. With other techniques, the patterns achieved have typically been two-dimensional, Eben Alsberg, a bioengineer at the University of Illinois, tells The Scientist in an email. Three-dimensional bioprinting permits much more control over signal presentation in 3D.

So far, researchers have created patches of tissue that mimic portions of certain organs but havent managed to replicate the complexity or cell density of a full organ. But its possible that in some patients, even a patch would be an effective treatment. At the end of 2016, a company called Organovo announced the start of a program to develop 3-D printed liver tissue for human transplants after a study showed that transplanted patches of 3-D printed liver cells successfully engrafted in a mouse model of a genetic liver disease and boosted several biomarkers that suggested an improvement in liver function.

Only in the past few years have researchers started to make headway with one of the biggest challenges in printing 3-D organs: creating vasculature. After the patches were engrafted into the mouses liver in the Organovo study, blood was delivered to it by the surrounding liver tissue, but an entire organ would need to come prepared for blood flow.

For any cells to stay alive, [the organ] needs that blood supply, so it cant just be this huge chunk of tissue, says Courtney Gegg, a senior director of tissue engineering at Prellis Biologics, which makes and sells scaffolds to support 3-D printed tissue. Thats been recognized as one of the key issues.

Mark Skylar-Scott, a bioengineer at the Wyss Institute, says that the problem has held back tissue engineering for decades. But in 2018, Sbastian Uzel, Skylar-Scott, and a team at the Wyss Institute managed to 3-D print a tiny, beating heart ventricle complete with blood vessels. A few days after printing the tissue, Uzel says he came into the lab to find a piece of twitching tissue, which was both very terrifying and exciting.

For any cells to stay alive, [the organ] needs that blood supply, so it cant just be this huge chunk of tissue.

Courtney Gegg, Prellis Biologics

Instead of printing the veins in layers, the team used embedded printinga technique in which, instead of building from the bottom of a slide upwards, material is extruded directly into a bath, or matrix. This strategy, which allows the researchers to print free form in 3-D, says Skylar-Scott, rather having to print each layer one on top of the other to support the structure, is a more efficient way to print a vascular tree. The matrix in this case was the cellular material that made up the heart ventricle. A gelatin-like ink pushed these cells gently out of the way to create a network of channels. Once printing was finished, the combination was warmed up. This heat caused the cellular matrix to solidify, but the gelatin to liquify so it could then be rinsed out, leaving space for blood to flow through.

But that doesnt mean the problem is completely solved. The Wyss Institute teams ventricle had blood vessels, but not nearly as many as a full-sized heart. Gegg points out that to truly imitate human biology, an individual cell will have to be within 200 microns of your nearest blood supply. . . . Everything has to be very, very close. Thats far more intricate than what researchers have printed so far.

Due to hurdles with adding vasculature and many other challenges that still face 3-Dprinted tissues, laboratory-built organs wont be available for transplant anytime soon. In the meantime, 3-D printing portions of tissue is helping accelerate both basic and clinical research about the human body.

Emma Yasinski is a Florida-based freelance reporter. Follow her on Twitter@EmmaYas24.

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Hyperbaric chamber therapy: Im under a lot of pressure and I love it! – The Guardian

February 26th, 2020 8:45 pm

I wonder what the pedalo does as I slip into a waffle robe Im at Bellecell, a central London molecular-wellness clinic that offers hyper-personalised science-based solutions to health this place could be a Bond villains laboratory on the moon.

I am standing in a hushed, blue-lit underground brick tunnel with Kubrick-white furnishings and so many fascinating toys: EMS suits, laser IVs, and what looks like an exercise bike built into a love boat, with a vacuum for your legs.

As distracting as these things are, I am here to try something specific: a hyperbaric oxygen chamber. I am fascinated by these things. Culturally, they have long been signifiers of megalomania, detachment and anxiety. Michael Jackson had one in his house, which isnt a great recommendation. The Olympian swimmer Michael Phelps is another fan. But what do these chambers actually do? Do you have to be called Michael to use one?

I climb into a plastic body bag in my hospital booties. Hyperbaric oxygen therapy involves breathing pure oxygen in a pressurised environment. The structure is a semi-circular cage with comfortable bedding, surrounded by thick plastic walls. Once I am inside, a technician inflates the bag. I am basically inside a balloon, which will be maintained at constant pressure, as I breathe 100% oxygen through a mask.

Hyperbaric chambers are mostly used to treat gas gangrene, carbon monoxide poisoning and the bends, while the medical uses of oxygen include wound-healing and reducing the risk of infection. Many people report feeling energised afterwards. I have some oral swelling following dental work, and am interested to see if that goes down.

For some, the close confinement and constant sound of pressurisation will be a recipe for a panic attack. For me, it is heaven. I am what you might call a claustrophile. I have always loved climbing into cupboards and corners, making dens and closing a door on the world. I fantasise about Japanese capsule hotels. Now, I lie and watch a zip close above me. There is a hissing noise. I adjust my oxygen mask and observe star-headed thumb screws being turned to calibrate the pressure. The gauge crawls upwards, my ears are getting stuffy. I swallow as it hits 4psi, equivalent to a depth of nine feet under water. Gazing at ambient blue through a hatch to the outside world, I imagine Im much deeper, packed into a nuclear missile on the undercarriage of a submarine. I am in my happy place.

The use of oxygen for performance-enhancement is mostly misunderstood. The effects of inhaling it are extremely short-lived. Athletes are often seen huffing cans of oxygen at the touchline, but science indicates that this is a mostly meaningless activity. Pressure makes all the difference. Under pressure, oxygen is dissolved in larger quantities in the blood plasma itself, not just the red blood cells. That means a much higher amount of the gas is transported into tissues that need it for healing, in theory mobilising stem cell release to repair the body quickly. It is definitely promising; the catch is, you would probably need a few treatments to see the benefit. At 160 an hour, post-workout muscle soreness probably isnt reason enough.

I thoroughly enjoy the experience for its own sake. Lulled by the pressure and soft lighting outside, I fall into a deep, restorative nap. After an hour, I emerge as wobbly as a newborn. I dont feel supercharged, admittedly. I feel drowsy, and absolutely starving. Im assured this is normal. I do feel astonishingly relaxed, though. The swelling inside my mouth reduces significantly over the next day, too, for which I can probably thank the chamber.

I would totally have one of these in my house. I miss the missile, but cant afford to go back. Instead, Im cursed to walk these normobaric streets, breathing 21% oxygen like everyone else, dreaming of when I had less freedom to move.

Walter White, eat your heart out Could I recreate the effect with hydrogen peroxide, bakers yeast and a tarp over the bath?

Wellness or hellness? Airs and graces. 5/5

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Doctors Are Injecting This Naturally-Derived Substance to Restore Hair Thicknessand Its Not PRP – NewBeauty Magazine

February 26th, 2020 8:44 pm

The most emotional issue my patients have is hair loss, says New York dermatologist Cheryl Karcher, MD below a jaw-dropping before-and-after photo shared to her Instagram page. On the left half of the photo shared is a young womans exposed hairlinethe hair is so thin and sparse, the entire scalp is visible wherever your eye is drawn. On the right side of the photo, the same woman, but with an almost unbelievable amount of thicker hair, and, somehow, a sense of renewed confidence.

The secret? A little thing called nanofat.

In the past we only had PRP to offer that had to be done three times or more. Sometimes it would work, sometimes it didnt. Now we have nanofat hair restoration, which needs to be done just once, and is much more effective way to treat hair loss and grow hair, explains Dr. Karcher.

You May Also Like: How Low Level Laser Therapy Actually Works to Thicken Hair

So what is nanofat? According to Dr. Karcher, its derived from our own adipose tissue, whereas the ever popular PRP is derived from our blood. Nanofat includes adipose-derived stromal vascular fraction, which contains stem cells as well as growth factors. PRP contains the growth factors released from platelets in the blood, she adds. The procedure itself involves extracting anywhere from 20 to 40 millilitersof fat, usually from the abdomen, then processing it through mechanical filters, before injecting.

Like PRP, the possibilities of what nanofat can help with doesnt stop at the hairline. After the nanofat is processed to the point where there is no fat left, only stem cells and growth factors, it is injected into the scalp, the face, the neck, the decollete, or to improve sun damage, skin pigmentation, decrease wrinkles, and of course grow hair, says Dr. Karcher.

When nanofat is used for hair restoration, Dr. Karcher says she first injects the nanofat, then injects the patients PRP on top of it to act as a fertilizer for the nanofat. Perhaps the best part? Theres little to no painDr. Karcher says the most pain patients feel is during the PRP injections, so the scalp is numbed topicallyand no downtime. When nanofat is used on the face, chest or other areas, Dr. Karcher warns there may be some downtime of erythema and swelling or bruising. If injected for [skin] rejuvenation via microneedling the downtime is only about 48 hours.

While Dr. Karcher has seen unparalleled results from nanofat hair restoration, it is only ideal for patients who have some hair still present on the scalppatients who are completely bald may not be ideal candidates for the procedure. The only time I ever use PRP for hair restoration now is in a patient that doesnt have enough fat to harvest. The nanofat is just one treatment and the results seem to be superior. However, as La Jolla, CA plastic surgeon Robert Singer, MD notes, there is no safety or efficacy data surrounding nanofat treatment as of press time.

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Rheumatoid Arthritis Associated With Increased Risk for Depression – Rheumatology Advisor

February 26th, 2020 8:43 pm

Resultsfrom 2 longitudinal cohort studies conducted in South Korea indicate asignificantly increased risk for depression among patients with rheumatoidarthritis (RA), with women and those >30 years of age displaying the highestrates. This is according to an article published in Rheumatology.

Investigatorsabstracted data from the Korean Health Insurance Review and Assessment Service National Sample Cohort (HIRA-NSC) from the years 2002-2013. The HIRA-NSC is apopulation-based cohort established by the National Health Insurance Service ofSouth Korea. HIRA-NSC queries demographics, health, and diagnostic data from >1million individuals randomly selected from South Koreas National HealthInsurance Database.

The present analyses included data from 114,369,638 medical claims filed by 1,125,691 patients. Patients with depression and/or RA were identified through their respective International Statistical Classification of Diseases version 10 (ICD-10) codes. Two studies were designed. Study I matched patients with depression 1:4 with cohort members without depression. Study matched patients with RA 1:4 with cohort members without RA. Matching in both studies was performed for age group, sex, income bracket, and region of residence. Cox proportional hazards models were used to calculate hazard ratios (HRs) for depression and RA in each study. HR calculations were adjusted for number of comorbidities.

StudyI enrolled a total of 38,087 patients with depression and 152,348 individualsin a control group. A greater proportion of the patients with depression(n=1260; 0.7%) had a diagnosis of RA compared with the control group (n=883;0.6%) (P =.02). However, the HR for RA was not significantly elevated inthe depression group compared with the control group.

StudyII enrolled a total of 7385 patients with RA and 29,540 individuals in acontrol group, of whom 408 (5.5%) and 1246 (4.3%) had a diagnosis of depression,respectively (P <.001). Patients with RA had significantly increasedrisk for depression compared to those in the control group without RA (HR,1.20; 95% CI, 1.07-1.34; P =.002). In subgroup analyses, patients withRA over 30 years of age had the greatest HRs for depression compared with theircontrol subgroups.

Specifically,patients with RA aged 30-59 years (HR, 1.17; 95% CI, 1.01-1.36; P =.036)and patients 60 years (HR, 1.29; 95% CI, 1.08-1.55; P =.006) hadsignificantly elevated risk for depression compared to controls in the same agebrackets. Women with RA, unlike men, also displayed significantly higherdepression risk compared with controls of the same gender (HR, 1.19; 95%,1.05-1.35; P =.006).

Theseresults suggest that while RA increases the risk for depression, this associationis not bidirectional. Women with RA and patients >30 years were particularlysusceptible to depression. Of note, data on RA and depression severity were notavailable, nor were data on smoking, alcohol consumption, or physical activity.As such, analyses may not have accounted for all possible factors contributing todepression. Even so, the elevated HRs for depression observed among RAsubgroups emphasize the need for mental health care access for patients withRA.

Reference

Kim SY, Chanyang M, Oh DJ, Choi HG. Association between depression and rheumatoid arthritis: two longitudinal follow-up studies using a national sample cohort [published online November 19, 2019]. Rheumatology (Oxford). doi:10.1093/rheumatology/kez559

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Voltaren Arthritis Pain Receives FDA Approval for Over-the-counter Sale: How Does It Compare to Other Topical Treatments? – DocWire News

February 26th, 2020 8:43 pm

The Food and Drug Administration (FDA) approved Voltaren Arthritis Pain (diclofenac sodium topical gel, 1%) for nonprescription, over-the-counter (OTC) use to treat osteoarthritis (OA)-associated pain. The medication was initially available through prescription; the change is possible through the FDAs prescription (Rx)-to-OTC switch process.

As a result of the Rx-to-OTC switch process, many products sold over-the-counter today use ingredients or dosage strengths that were available only by prescription 30 years ago, said Karen Mahoney, MD, acting deputy director of the Office of Nonprescription Drugs in the FDAs Center for Drug Evaluation and Research, in an FDA press release. Approval of a wider range of nonprescription drugs has the potential to improve public health by increasing the types of drugs consumers can access and use that would otherwise only be available by prescription. This includes providing the millions of people that suffer with joint pain from arthritis daily over-the-counter access to another non-opioid treatment option.

Voltaren Arthritis Pain, formerly known as Voltaren Gel 1%, received initial FDA approval in 2007. It is not intended for immediate relief; patients should allow up to seven days to feel its effects. If patients feel no change after seven days or are still using the product after 21 days, it is recommended that they terminate use and seek medical attention.

Voltaren Arthritis Pain is a non-steroidal anti-inflammatory drug (NSAIDs). A study published in The BMJ linked NSAIDs to increased heart failure risk, with seven posing the most significant risk; one of these NSAIDs was diclofenac.

The Voltaren website describes the drug, Diclofenac sodium is a nonsteroidal anti-inflammatory drug (NSAID) that is often used to treat arthritis pain. It falls in the same class (NSAID) as drugs such as ibuprofen (Advil) and naproxen (Aleve). Diclofenac works by temporarily blocking the production of pain signaling chemicals called prostaglandins.

Unlike Voltaren Arthritis Pain, Biofreeze pain relief gel and Salonpas deep relieving gel are not NSAIDs; they are both considered topical rubefacients. They are not prescribed specifically for OA-related pain. Salonpas is sold OTC, and Biofreeze is available OTC and by prescription.

According to drugs.com, there are no known drug interactions associated with Biofreeze. Eleven drugs are associated with minor interactions in Salonpas. An estimated 111 drugs are known to interact with Voltaren Arthritis Pain Gel: seven major, and 104 moderate.

There are no known disease interactions associated with Biofreeze or Salonpas. Voltaren Arthritis Pain is reportedly known to interact with asthma, renal dysfunction, heart failure, hypertension, and platelet aggregation inhibition.

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Nursing homes can’t administer medical cannabis. This bill would change that. – wtvr.com

February 26th, 2020 8:43 pm

RICHMOND, Va. -- Virginia lawmakers continue to fine tune legislation that aligns with the states growing medical cannabis program by advancing two Senate bills facilitating the work of caregivers and lab employees.

SB 185 sponsored by Sen. Siobhan Dunnavant, R-Henrico, would allow employees at nursing homes, assisted living facilities and hospices to administer CBD and THC-A oil to residents who have a valid written certification to use the medication. SB 885 from Sen. David W. Marsden, D-Fairfax, would remove criminal liabilities for analytical lab workers who transport and possess both substances during the course of their work.

Marsden also introduced legislation to protect individuals from possession charges for having marijuana in the form of cannabidiol oil or THC-A oil, if they have valid written certification from a practitioner.

In 2019, Dunnavant and Marsden helped pass legislation signed by the governor to reduce restrictions for patient access to the substances (SB 1557 , SB 1719]).

CBD products are used to treat epilepsy and to help with pain management for a variety of ailments. The product can be extracted from hemp, a plant in the cannabis family that is typically low in THC. The non psychoactive version of THC is THC-A; it does not produce a high. THC-A has been used to treat seizures, arthritis and chronic pain. Fibers of the hemp plant are also used in making rope, clothing, paper and other products. Hemp recently became legal [vox.com] at the federal level, and its cultivation is still regulated].

There is a distinction between hemp-derived CBD oil and marijuana-derived CBD oil, namely the level of THC present.

Dunnavant told a Senate panel that the bill is needed so that staff at assisted living facilities can be included as those authorized to store and administer both CBD and THC-A to residents and patients. Registered nurses and licensed practice nurses can legally administer the oils. Last year lawmakers passed legislation protecting school nurses from prosecution for possessing or distributing such oils, in accordance with school board policy.

Several nursing homes and assisted living facilities when contacted said that currently the use of CBD or THC-A are not allowed at their locations and that there are no immediate plans to incorporate such use into the care of their residents or patients.

Marsden sees his bill as an opportunity for further research and development of medical marijuana in Virginia. The state pharmaceutical processors permitted to manufacture and dispense marijuana-derived medications can distribute products with doses that do not exceed 10 milligrams of THC.

If a laboratory is going to handle a drug that is marijuana, they need immunity from prosecution. Marsden said. Even if we go into decriminalization, that still has some civil penalties for it.

Richmonder Brion Scott Turner is glad that steps are being made towards CBD becoming more available. Turner uses CBD to help with his own medical condition.

I use a CBD infused lotion for my psoriasis, Turner said. It gives me relief from the itching and the psoriatic arthritis that comes with it.

Turner has said that most of his friends and family use CBD to help with a variety of ailments from minor headaches to anxiety attacks.

My mother uses CBD for anything from lower back pain, helping with an upset stomach or even migraines, Turner said.

Other cannabis related bills moving through the General Assembly include HB 972 , which would decriminalize simple possession of marijuana down to a civil penalty of no more than $25. The Senate version [lis.virginia.gov] of the bill carries a civil penalty of no more than $50.

HJ 130, currently in the Senate Committee of Rules, would direct the Joint Legislative Audit and Review Commission to study options for the regulation of recreational adult use and medical use of cannabis. SJ 67 , which has passed the House and Senate, directs JLARC to study options and make recommendations for how Virginia should go about the growth, sale and possession of marijuana. JLARCs recommendations are due by July 1, 2022.

Both Dunnavant and Marsdens bills reported out of committee and are headed to the House floor.

By Chip Lauterbach/Capital News Service

Capital News Service is a flagship program of VCUs Robertson School of Media and Culture. Students participating in the program provide state government coverage for Virginias community newspapers and other media outlets, under the supervision of Associate Professor Jeff South.

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Arthritis, muscle and spinal service success in Barrow – NW Evening Mail

February 26th, 2020 8:43 pm

A SERVICE for people with arthritis, hip and knee conditions, joint and muscle injuries and spinal pain is proving to be a success with around 5,000 patients using it last year.

The main aim of the Integrated Musculoskeletal Service is to ensure that patients are seen by the right person first time. The service is involving and supporting patients to make the right decision, for themselves, about their treatment - for example by highlighting alternative treatments to hip and knee surgery.

The aim of the service is to get it right first time for our patients and to support them to choose the right treatment for their condition, said James Geary, extended scope physiotherapist. Weve had some great feedback from our patients which is positive.

The service is provided by the University Hospitals of Morecambe Bay NHS Foundation Trust which runs Furness General.

Patient feedback has included:

Considerate and quick. Someone who listened well and sorted out the problem. I wanted a good explanation about what was happening with my body and I got it. Thank you.

The team has expanded its specialist clinics for those with musculoskeletal problems across the following sites: Westmorland General Hospital, Ulverston Community Health Centre, Grange Health Centre, Heysham Primary Care Centre, Alfred Barrow Health Centre, Furness General Hospital, Royal Lancaster Infirmary, Millom Health Centre and Queen Victoria Hospital in Morecambe.

This new way of working is another example of Bay Health and Care Partners working together more effectively to provide better care in the community, which will keep people across Morecambe Bay healthier and at home for longer without having to come into hospital.

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TLR4 Blockade May Not Treat RA With Inadequate Response to MTX – Rheumatology Advisor

February 26th, 2020 8:43 pm

The toll-like receptor 4 (TLR4) pathway is not likely arelevant target in treating patients with rheumatoid arthritis (RA) whodemonstrate an inadequate response to methotrexate therapy, according toresearch published in the Annals of the Rheumatic Diseases.

Researchers conducted a phase 2, proof-of-concept, randomized, placebo-controlled, double-blind, international, multicenter study of patients with moderate to severe anticitrullinated protein antibody-positive RA who previously demonstrated an inadequate response to methotrexate therapy. The study included adults with active RA 6 months who fulfilled the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria.

In total, 250 patients were screened for eligibility and 90were randomly assigned to receive either placebo (n=29) or 5 mg/kg NI-0101 afirst-in-class humanized monoclonal antibody-blocking TLR4 every 2 weeks for12 weeks (n=61). All participants also continued methotrexate therapy. Fromeach group, 57 and 29 patients (from treatment and control group, respectively)completed both the 12-week visit and the follow-up phase through week 24.

Overall, no major differences were noted between groups interms of individual disease parameters, although patients in the NI-0101 grouphad a longer RA duration (8.5 vs 5.4 years) and were younger at the time ofdiagnosis (45.7 vs 51.2 years). The mean C-reactive protein (CRP) level wasalso higher in this group at baseline (18.3 mg/L vs 13.4 mg/L).

Both treatment groups demonstrated similar decreases frombaseline to week 12 disease activity scores in 28 joints with CRP, with nosignificant between-group differences noted. Both Clinical Disease ActivityIndex and Simplified Disease Activity Index scores decreased approximately 40%from baseline to 12 weeks, and the proportion of patients who achieved good ormoderate EULAR responses increased with treatment.

By week 12, 27.6% and 26% of patients in both groups(placebo and NI-0101, respectively) achieved good EULAR responses whereas 55.2%and 53.6%, respectively, achieved EULAR moderate responses. Similarly, nosignificant between-group differences were noted in ACR responses at week 12,with 55.2% in the placebo group and 58.9% in the treatment group achieving improvement of 20% in ACRcriteria responses, 20.7% and 14.3% achieving improvement of 50% in ACR criteria (ACR50)responses, and 10.3% and 10.7% achieving improvement of 70% in ACR criteria responses. Asubgroup analysis found no significant effects on stratification by either CRPor FcRIIa genotype for either disease activity score in 28 joints with CRP orACR50 response.

A pharmacokinetics profile of NI-0101 showed expectedconcentrations and elimination consistent with simulations. NI-0101concentrations were maintained above the targeted threshold of 10,000 ng/mL ina majority of patients. In terms of pharmacodynamics, no significantdifferences between treatment groups were noted for all evaluated biomarkers.

NI-0101 infusions every 2 weeks demonstrated an acceptablesafety and tolerability profile in patients with RA, with similar proportionsof treatment-emergent adverse events occurring in both the placebo andtreatment groups (51.7% and 52.5%, respectively). The most frequently reportedadverse events were infections (13.8% in the placebo group and 11.5% in theNI-0101 group).

The lack of significant effect of NI-0101 in thiswell-controlled prospective clinical trial indicates that blocking the TLR4pathway alone is unlikely to benefit patients with established RA, theresearchers concluded. The good NI-0101 safety and [pharmacokinetic]profiles support further exploration in other diseases.

Disclosure: Thisclinical trial was supported by Novimmune SA. Please see the original referencefor a full list of authors disclosures.

Reference

Monnet E, Choy EH, McInnes I, et al. Efficacy and safety of NI-0101, an anti-toll-like receptor 4 monoclonal antibody, in patients with rheumatoid arthritis after inadequate response to methotrexate: aphase II study [published online December 31, 2019]. Ann Rheum Dis. doi: 10.1136/annrheumdis-2019-216487

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FDA Approves Opioid Treatment Option – Rheumatology Network

February 26th, 2020 8:43 pm

The U.S. Food and Drug Administration has approved the use of an intravenous form of the pain reliever meloxicam (Anjeso, Baudax Bio) for the relief of moderate to severe pain.

Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) currently available in tablet form as Mobic by Boehringer Ingelheim. It is approved for the relief of pain associated with osteoarthritis and rheumatoid arthritis in adults, and in children two years and older who have juvenile rheumatoid arthritis.

Now, it can be administered as a once a day, 24-hour intravenous NSAID treatment for patients with moderate to severe pain.

The active ingredient in meloxicam is a long-acting, preferential COX-2 inhibitor with analgesic, anti-inflammatory and antipyretic activities, which inhibits COX-2 thereby reducing prostaglandin biosynthesis.

The approval of Anjeso marks a major advancement in the treatment landscape for managing moderate to severe pain. With our nation currently in the midst of a national opioid epidemic, we are thrilled to be able to offer a novel, non-opioid therapeutic option with the potential to meaningfully impact the acute pain treatment paradigm," said Gerri Henwood, president and chief executive officer of Baudax Bio, in a press statement.

The company cited the success several mid to late stage clinical trials on Anjeso, plus a recent phase three safety trial that showed the treatment was well tolerated as an option to opioids.

While traditional opioid medications have proven effective at providing pain relief, the associated adverse side effects, including sedation and respiratory depression, have driven physicians to employ a multi-modal approach to treating post-operative pain. With 24-hour, durable pain relief and a safety profile comparable to placebo, Anjeso has the potential to serve as a meaningfully differentiated analgesic alternative, said the University of Miami's Keith Candiotti, M.D., in a written statement.

The Anjeso approval is supported by two phase three efficacy studies, one double-blind, placebo-controlled phase three safety study and four phase two clinical studies. A randomized multicenter, double-blind, placebo-controlled phase three study of 379 orthopedic surgery patients showed that patients receiving once-daily intravenous meloxicam 30 mg for seven days required fewer opioids. Total opioid consumption (36.8 mg versus 50.3 mg IV morphine equivalent dose) and opioid consumption from zero to 24 hours, 2448 hours, zero to 48 hours, and zero to 72 hours were statistically significantly lower in the meloxicam treatment group. The side effects were reported as mild to moderate and affected 65 percent of patients.

The most common adverse reactions reported in at least 2 percent of patients treated with Anjeso and at a greater frequency than placebo included: constipation, gamma-glutamyl transferase increased and anemia.

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Is It Too Late to Buy High-Flying Galapagos? – Motley Fool

February 26th, 2020 8:43 pm

Galapagos(NASDAQ:GLPG) galloped to all-time highs heading into this week. Although a pullback in the overall market has caused the biotech to give up some of its gains, Galapagos is still up close to 20% year to date and up around 150% over the past 12 months.

Some investors could view Galapagos as valued at a steep premium after its big run-up. But is it really too late to buy the high-flying biotech stock?

Image source: Getty Images.

The primary catalyst behind Galapagos' meteoric rise over the last year was its major collaboration deal signed with Gilead Sciences (NASDAQ:GILD) in July last year. Gilead forked over $5.1 billion for the 10-year agreement, with a $3.95 billion upfront payment and a $1.1 billion equity investment in Galapagos.

Gilead and Galapagos were already partnering on immunology drug filgotinib. The new deal gave Gilead the rights to Galapagos' other late-stage pipeline candidate, idiopathic pulmonary fibrosis (IPF) drug GLPG1690. In addition, Gilead can exercise an option to license any of Galapagos' other candidates.

You can attribute Gilead's interest in Galapagos to the tremendous promise for filgotinib. The experimental drug sailed through late-stage clinical studies targeting rheumatoid arthritis with flying colors. Gilead and Galapagos filed for U.S. and European regulatory approvals for filgotinib in treating rheumatoid arthritis in 2019. Approvals are anticipated later this year in the indication.

And that could be just the start. Gilead and Galapagos are also evaluating filgotinib in other late-stage clinical studies in treating Crohn's disease, psoriatic arthritis, and ulcerative colitis. It's also in phase 2 clinical studies targetingankylosing spondylitis and other inflammatory diseases.

Just how successful filgotinib could be if it wins approval remains to be seen. But peak annual sales of close to $3 billion in treating rheumatoid arthritis and another $3 billion in treating other immunology indications could be possible. Filgotinib's safety profile and convenience (it's an oral medication instead of an injection) could boost its commercial success.

That kind of market potential might make Galapagos' current market cap of under $16 billion seem like a steal. However, it's important to remember that the biotech won't rake in all of the money that filgotinib could make.

Galapagos will market filgotinib on its own inBelgium,the NetherlandsandLuxembourg. It willsplit profits generated by filgotinib equally with Gilead in France,Germany,Italy,Spain, and theUnited Kingdom. In other countries, Galapagos stands to receive tiered royalties between 20% and 30%.

Based on AbbVie'sexperience with blockbuster drug Humira prior to it losing exclusivity in Europe, I expect somewhere around two-thirds of filgotinib's sales will be made in the U.S. If we use a peak annual sales estimate of $6 billion, that would give Galapagos a maximum of $1.2 billion from U.S. sales of the drug. Outside of the U.S., my back-of-the-napkin estimate is that Galapagos would make a little under $1 billion annually.

It's more difficult to predict the financial impact for Galapagos' other drugs. Galapagos thinks that the global market for IPF could be $5 billion by 2025. If we assumedGLPG1690 could capture half of that market, Galapagos would probably make around $750 million annually at peak sales due to its licensing deal with Gilead.

My numbers are admittedly very rough. However, I think that peak revenue from filgotinib andGLPG1690 could bring in somewhere in the ballpark of $3 billion for Galapagos in the future. The company's other earlier-stage programs could boost its sales. In addition, Galapagos is eligible to receive some hefty milestone payments from Gilead if all goes well.

Still, though, we're looking at a stock that currently trades at more than five times sales that it might achieve sometime in the future. I like the potential for Galapagos' products. However, I think that there are other biotech stocks with more room to run. My view is that it is a little too late to jump on the Galapagos bandwagon.

Excerpt from:
Is It Too Late to Buy High-Flying Galapagos? - Motley Fool

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Tis the Season? Study Examines Effect of Time of Year on Primary Sjgrens Syndrome Symptoms – DocWire News

February 26th, 2020 8:43 pm

A new study examined whether season has an impact on symptoms of fatigue, pain, and dryness in primary Sjgrens syndrome.

Seasonality in rheumatic diseases is an issue frequently perceived and voiced by patients. Several studies have identified weather-related flares in rheumatoid arthritis (RA). Weather conditions might also influence pain and function in osteoarthritis, and a seasonal pattern in gout incidence has been described, the researchers wrote.

However, seasonality has not been investigated in primary Sjgrens syndrome (pSS) yet.

The present study evaluated patient data from the French nationwide multicenter pSS cohort Assessment of Systemic Signs and Evolution in Sjgrens Syndrome (ASSESS) (n=395). ASSESS was created in 2006 and houses five-year prospective follow-up data as well as data from three randomized, placebo-controlled trials of infliximab (TRIPSS) (n=103; 22 weeks of follow-up; seven visits), rituximab (TEARS) (n=120; 24 weeks of follow-up; six visits), and hydroxychloroquine (JOQUER) (n=120; 48 weeks of follow-up; four visits). In each study, visits included data collection on visual analog scale (VAS) scores for pain, fatigue, and dryness. In the ASSESS group, objective assessments of dryness were taken at baseline and again at two and five years. Data were assessed by the day, month of the year, and season.

Final analysis included 632 Sjgrens syndrome patients and a total of 2,858 VASs observations spanning the four studies. VASs collected for Sjgrens syndrome patients by season were: spring, 744; summer, 584; fall, 848; and winter, 682. VAS scores for pain were as follows: spring, 52.2; summer, 55.1; fall, 51.0; and winter, 51.7. VAS fatigue scores were 61.9, 62.2, 60.0, and 61.9, respectively; VAS scores for dryness were 58.9, 61.2, 56.9, and 57.9, respectively.

The EULAR Sjgrens Syndrome Patient Reported Index scores did not significantly differ by season: spring, 57.7; summer, 59.5; fall, 55.9; and winter, 57.2.

The results of the study were published in Arthritis Research &Therapy.

The researchers concluded, This first large study on seasonality in [primary Sjgrens syndrome] provides new evidence that fatigue, pain and dryness, as well as the ESSPRI score, do not have meaningful fluctuations according to months or seasons. In [primary Sjgrens syndrome], seasonality does not affect patient-reported outcomes (PROs) on fatigue, pain and dryness.

Continued here:
Tis the Season? Study Examines Effect of Time of Year on Primary Sjgrens Syndrome Symptoms - DocWire News

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Equine Back Pain: Dr. Kent Allen’s Bag of Diagnostic and Treatment Tricks – TheHorse.com

February 26th, 2020 8:43 pm

Compelling, controversial, and complicated. Thats how Kent Allen, DVM, of Virginia Equine Imaging, in The Plains, describes the equine back. The veterinary community continually debates equine back pain, which he said can be difficult to diagnose with standard approaches and imaging techniques.

Allen knows equine backs well. He has extensive experience treating high-performance horses in his practice and leadership roles at the Olympic, Pan American, and World Equestrian Games. Hes presented diagnostic and treatment methods for many International Society of Equine Locomotor Pathology (ISELP, for which he serves as vice president and executive director) modules around the world and at the American Association of Equine Practitioners convention.

Allen shared his back-pain workup and treatment recommendations with equine veterinarians at the 11th annual Northeast Association of Equine Practitioners (NEAEP) symposium, held Sept. 25-28, 2019, in Saratoga Springs, New York.

First Allen reviewed spinal anatomy, reminding veterinarians about variation in the thoracic and lumbar vertebrae running from the withers to the pelvis. Typically, horses have 18 thoracic (sometimes 19 and rarely 17) and six (occasionally five) lumbar vertebrae. He doesnt use markers on back radiographs to identify specific vertebrae, opting rather to look for the anticlinalthe vertebra at which the spine orientation changeswhich is usually the 15th thoracic vertebrae (T15, though occasionally T14).

T12 is usually the base of the withers, he explained, and the anticlinal is usually T15. Veterinarians can identify the thoracolumbar junction (between the thoracic and lumbar vertebrae) by looking at the change in rib curvature and the transverse processes, which are the protrusions from the sides of the vertebrae. Other helpful anatomical landmarks include the tuber coxaethe point of the hipwhich blocks veterinarians radiographic view of L4-6 (sometimes 5-6, he said). Thats also where articular processes begin to appear more upright.He pointed out the fused mammillary processes, where horses get arthritic change, off the articular processes and in the facet jointwhere the vertebral bodies come together.

We want to understand (the anatomy) before we start trying to diagnose it and treat it, he said, emphasizing that vets also must thoroughly understand the epaxial musculature, the multifidus muscle, longissimus muscle, intraspinous ligament (in which you can see some bony changes that arent usually associated with pathologydisease or damage), and the supraspinous ligament (which can be injured but usually a relatively minor issue thats easy to treat).

The multifidus, which attaches on the articular areas right beside the mammillary processes and reaches forward two or three vertebrae, is crucial because it is responsible for balancing and tensioning that back, he said. And, so, the more you fatigue or have pathology in the back and the more you get multifidus loss of the musculature, the more pressure and weight you put on the longissimus and the more the entire system fails.

Typical back problems Allen and his colleagues see in their practice include:

Bucking is common in horses with back pain, Allen said. Vets should ask themselves, Is it lame? Does the lameness have anything to do with the back (which is rare)? Usually its a decreased performance complaint.

Allen performs a detailed clinical exam on each horse fitting this description; he palpates the back and mobilizes its structures in a dynamic exam, watching the horse walk and jog. He emphasized that horses with back pain come in all shapes and sizes, and some might be very stoic and not show signs of problems until theyre performing at a very high level, sometimes even very late in their athletic careers.

These horses can jump, they can do their jobs, said Allen, citing an upper-level equine athlete he treatedone with significant overriding dorsal spinous processes that had gone undetected until the horse developed severe back pain late in his eventing career. Once we figured out his problem and gave him some pain relief, he looked a lot better doing his job.

Other horses are more demonstrative and will take your kneecap off if you press around on their backs, he said.

For horses not about to kick you in the kneecap, said Allen, he uses a surcingle weighted with 60 pounds to evaluate pain level while the horse is longed in a round pen. I get to see (the horse) move without the weighted surcingle and with the weighted surcingle without the riders influence, he said.

In videos he showed how a horse wearing the weighted surcingle stiffened, accentuating his lameness.

We use this a lot; we dont go through a day without putting this on several horses, he said.

Once Allen and his colleagues have determined without a doubt the horse is experiencing back pain, he turns to imaging, beginning with lateral radiographic views of the spine. He also uses nuclear scintigraphy (bone scans). But he cautioned that any imaging can reveal irrelevant dorsal articular remodeling. In other words, he and other veterinarians see damage in many backs that never creates pain.

In fact, several good studies show there are a lot of orthopedic back problems in horses that show no pain in the back, he said. And so youre left wondering if these horses have pathology and theyre not back sore, then what the heck are you doing X raying them and bone scanning them if theres no correlation between the imaging and the clinical? And the answer is, its really hard to figure it out.

You have got to tie the clinical to the imaging, he added, telling veterinarians to first ask themselves in back pain cases how the injury happened. (Researchers) proved years ago that kissing spines without a doubt is developmental, and it worsens with time. Now, no one has really proven one way or another about the facet arthritis, but I suspect its the exact same thing.

Whether a horse experiences and shows pain from the pathology depends on what the horse is asked to do, he said. For example, in one study veterinarians found severe bone pathology in a group of racehorses euthanized for reasons besides back pain. But, had the horses all become jumpers, many might have exhibited pain they didnt show as racehorses, he reasoned.

The question is, does the horse have the developmental abnormalities, which most of the time were never going to know, is it old enough to have this problem, does it have a job that is going to exacerbate the problem? he said. And, then, you as clinicians can start putting the picture together.

Additionally, Allen said he and his colleagues commonly see horses that are both lame and back sore, generally for separate problems requiring treatment.

Once Allen has confirmed the pathology in the back is, in fact, the cause of the pain, he applies the following treatments:

Secondary treatments include light ridden or in-hand work for short periods. In fact, Allen said its key to avoid long rest periods, opting instead to avoid muscle wasting by returning horses to work.

Extracorporeal shock wave therapy is a big part of his treatment approach. What were really doing with it is quite different from what were doing with treating a proximal suspensory (ligament injury in the leg), he said. There, were trying to stimulate all kinds of healing pathways . Here (with backs) what were trying to do is downregulate pain receptors normal bone has very few pain receptors in it, but arthritic bone has a lot.

We tend to use 1,000 to 2,000 pulses, depending on whether we know where the problem is, and typically we repeat it at five- to six-month intervals, but its variable depending on the patient, he added. Weve been very successful with managing these upper-level athletes with ESWT.

Allen and his colleagues commonly use ESWT and mesotherapy synergistically if the back injury is soft-tissue-related only.

As for other treatment approaches, Allen referenced a study Denoix et al. conducted with the bisphosphonate tiludronate disodium (Tildren). It maybe wasnt the greatest in statistical significance, but 80% of the horses treated with Tildren showed improvement by Day 60, compared with 50% of the control group, he said. So definitely on arthritis in that area, this is a study that you can point at and say, Well, theres a rationale for giving these horses Tildren.

Allen said while several studies support acupuncture for treating backs, this approach as well as chiropractic dont last very long. They last about three weeks, he said. We need something that lasts months and months, or longer.

In an unpublished study Allen and his colleagues looked at 314 horses presented for back pain. Of those, 57 were also presented for lameness. When veterinarians examined the horses, they considered only 32% as lame, but 92% as positive to back palpation and 90% as having a positive response to the weighted surcingle. Some other notes he made:

I dont understand why we want to rush to do surgery because you can manage these horses very effectively with medical therapy, he said. Medical management of back pain and pathology is very successful at keeping these horses going and going at their level of work, not dropping down and doing something lesser.

Theres one exception to that the horses that have already presented with avoidance behavior, he added. And if that avoidance behavior includes bucking the riders off now you have a physical problem and a mental problem. Once that horse has decided that his default response to back pain is bucking the rider off, you can treat that horse and you can be very successful. But what you dont know is at what moment four months from now thats all going to wear off and that horse is going to turn into a horse trying to be the star of the Calgary Stampede.

His biggest take-home message? Veterinarians must see horses with back pain in the field, diagnose them, and start medical management early. If you wait till they start bucking, the prognosis plummets, he said.

The (combination of) technology and the education is there to do it now, he added. It wasnt 15 years ago, but it is now. And, so, you can X ray the dorsal spinous processes, you can have (horses) sent to a clinic and you can X ray the entire spine and know what youre looking at, you can do bone scans, and you can learn to ultrasound these articular processes and the osteoarthritis. These horses dont have to keep going, and you have to educate your riders that when this horse starts getting back sore, weve got to see it and weve got to figure it out.

Continued here:
Equine Back Pain: Dr. Kent Allen's Bag of Diagnostic and Treatment Tricks - TheHorse.com

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Mice with diabetes "functionally cured" using new stem cell therapy – New Atlas

February 26th, 2020 8:42 pm

Diabetes is characterized by trouble producing or managing insulin, and one emerging treatment involves converting stem cells into beta cells that secrete the hormone. Now, scientists have developed a more efficient method of doing just that, and found that implanting these cells in diabetic mice functionally cured them of the disease.

The study builds on past research by the same team, led by Jeffrey Millman at Washington University. The researchers have previously shown that infusing mice with these cells works to treat diabetes, but the new work has had even more impressive results.

These mice had very severe diabetes with blood sugar readings of more than 500 milligrams per deciliter of blood levels that could be fatal for a person and when we gave the mice the insulin-secreting cells, within two weeks their blood glucose levels had returned to normal and stayed that way for many months, says Millman.

Insulin is normally produced by beta cells in the pancreas, but in people with diabetes these cells dont produce enough of the hormone. The condition is usually managed by directly injecting insulin into the bloodstream when its needed. But in recent years, researchers have found ways to convert human stem cells into beta cells, which can pick up the slack and produce more insulin.

In the new study, the team improved that technique. Usually when converting stem cells into a specific type of cell, a few random mistakes are made, so some other types of cells end up in the mix. These are harmless, but arent exactly pulling their weight for the job at hand.

The more off-target cells you get, the less therapeutically relevant cells you have, says Millman. You need about a billion beta cells to cure a person of diabetes. But if a quarter of the cells you make are actually liver cells or other pancreas cells, instead of needing a billion cells, youll need 1.25 billion cells. It makes curing the disease 25 percent more difficult.

So, the new method was focused on reducing those unwanted extras. By targeting the cytoskeleton, the underlying structure that gives cells their shape, the team was able to not only produce a higher percentage of beta cells, but they also functioned better.

Its a completely different approach, fundamentally different in the way we go about it, said Millman. Previously, we would identify various proteins and factors and sprinkle them on the cells to see what would happen. As we have better understood the signals, weve been able to make that process less random.

When these new-and-improved beta cells were infused into diabetic mice, their blood sugar levels were stabilized, rendering the diabetes functionally cured for up to nine months.

Of course, at this stage its just an animal trial, so the results may not translate to humans any time soon, if ever. But the researchers plan to continue the work by testing the cells in larger animals over longer periods, with hopes of one day getting the treatment ready for human clinical trials.

The research was published in the journal Nature Biotechnology.

Source: Washington University

Continued here:
Mice with diabetes "functionally cured" using new stem cell therapy - New Atlas

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Mice with diabetes functionally cured using new stem cell therapy – Daily Times

February 26th, 2020 8:42 pm

The study builds on past research by the same team, led by Jeffrey Millman at Washington University. The researchers have previously shown that infusing mice with these cells works to treat diabetes, but the new work has had even more impressive results.

These mice had very severe diabetes with blood sugar readings of more than 500 milligrams per deciliter of blood levels that could be fatal for a person and when we gave the mice the insulin-secreting cells, within two weeks their blood glucose levels had returned to normal and stayed that way for many months, says Millman.

Insulin is normally produced by beta cells in the pancreas, but in people with diabetes these cells dont produce enough of the hormone. The condition is usually managed by directly injecting insulin into the bloodstream when its needed. But in recent years, researchers have found ways to convert human stem cells into beta cells, which can pick up the slack and produce more insulin.

In the new study, the team improved that technique. Usually when converting stem cells into a specific type of cell, a few random mistakes are made, so some other types of cells end up in the mix. These are harmless, but arent exactly pulling their weight for the job at hand.

The more off-target cells you get, the less therapeutically relevant cells you have, says Millman. You need about a billion beta cells to cure a person of diabetes. But if a quarter of the cells you make are actually liver cells or other pancreas cells, instead of needing a billion cells, youll need 1.25 billion cells. It makes curing the disease 25 percent more difficult.

So, the new method was focused on reducing those unwanted extras. By targeting the cytoskeleton, the underlying structure that gives cells their shape, the team was able to not only produce a higher percentage of beta cells, but they also functioned better.

Its a completely different approach, fundamentally different in the way we go about it, said Millman. Previously, we would identify various proteins and factors and sprinkle them on the cells to see what would happen.

As we have better understood the signals, weve been able to make that process less random.

When these new-and-improved beta cells were infused into diabetic mice, their blood sugar levels were stabilized, rendering the diabetes functionally cured for up to nine months.

Of course, at this stage its just an animal trial, so the results may not translate to humans any time soon, if ever. But the researchers plan to continue the work by testing the cells in larger animals over longer periods, with hopes of one day getting the treatment ready for human clinical trials.

The research was published in the journal Nature Biotechnology.

Continued here:
Mice with diabetes functionally cured using new stem cell therapy - Daily Times

Read More...

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