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03-23-2019 07:21 AM
s) - The U.S. Food and Drug Administration declined to approve a drug developed by Sanofi SA and Lexicon Pharmaceuticals Inc intended for use with insulin in patients with type 1 diabetes, the companies said on Friday.
The decision comes about two months after an FDA advisory panel failed to reach a consensus over whether the once-daily oral drug, sotagliflozin, should be approved as an add-on to insulin therapy.
The setback comes as Sanofi works to revive declining sales from its diabetes division, and as the French drugmaker faces increasing pressure from politicians and patient advocacy groups over the rising cost of its insulin products.
Sotagliflozin, works by inhibiting the proteins SGLT1 and SGLT2 to help regulate blood glucose levels and reduce the risk of weight gain.
Wedbush analyst Liana Moussatos had forecast annual U.S. sotagliflozin sales exceeding $450 million for type 1 diabetes by 2024.
The FDA panel members in January had raised concerns of the risk of diabetic ketoacidosis (DKA), leaving them divided over whether the treatment's benefits outweighed the risks.
DKA is a life-threatening condition in which acids called ketones build up when the body starts to use fat instead of glucose as a source of energy.
The companies had proposed a risk evaluation and mitigation strategy (REMS) for the drug and have said regular testing of ketone levels should be required.
Other SGLT2 inhibitors, AstraZeneca's Farxiga, Johnson & Johnson's Invokana and Eli Lilly and Co and Boehringer Ingelheim's Jardiance, are approved for type 2 diabetes. They work by removing excess blood sugar through the urine and also cause some weight loss.
Type 1 diabetes affects about 1.3 million Americans, according to the American Diabetes Association.
Sanofi and Lexicon said they will work with the FDA to determine the appropriate next steps.
(Reporting by Manojna Maddipatla and Tamara Mathias in Bengaluru; editing by Bill Berkrot)
03-23-2019 07:38 AM
Diabetes Research Institute Scientists Engineer ‘Suicide Genes’ to Safely Grow Insulin-Producing Beta Cells from Stem Cells
Double fail-safe approach may help advance cell-replacement therapies for type 1 diabetes
MIAMI, FL – February 19, 2019 -- Researchers have been advancing methods to generate insulin-producing beta cells from pluripotent stem cells (PSC) for the clinical treatment of type 1 diabetes (T1D). However, transplantation of these immature cells into patients poses substantial risks, namely the development of tumors (teratomas) and the growth of these stem cells into unwanted cell types. Pluripotent stem cells are known to develop into all of the body’s cells and tissues.
|Colony of stem cells genetically modified with a double fail-safe mechanism to control the formation of tumors and the differentiation into non-desirable cell types. Cells are stained for the stem cell markers SOX2 (green) and TRA-1-60-R (red). A nuclear marker is shown in blue.|
Now, for the first time, scientists from the Diabetes Research Institute (DRI) at the University of Miami Miller School of Medicine have engineered a human pluripotent stem cell line containing two ‘suicide genes’ that induce cell death in all but the desired insulin-producing cells. This double fail-safe approach, published online ahead of the March 5 issue of Stem Cell Reports, addresses the limitations of PSC-derived beta cells and opens the door to creating safe cell-replacement therapies for people living with T1D.
Looming Clinical Trials Warrant Safeguards
With clinical trials already initiated using PSC-derived beta cell progenitors and newer approaches with functional beta-like cells on the horizon, the need to ensure patient safety is of paramount importance. Research has shown that only about 30 – 40 percent of beta-like cells are obtained through current PSC differentiation (development) protocols, leaving a significant percentage of undefined cells in the balance. Most importantly, non-differentiated cells – cells that have not yet developed into a specific type – may produce tumors upon transplantation, despite recent protocol refinements.
To address these concerns, the DRI team set out to engineer pluripotent stem cell lines that selectively destroy both tumorigenic cells and cells that do not produce insulin, like liver, brain, muscle cells and others. The team tested their approach both in vitro and in vivo in a mouse model of diabetes that mimics the disease condition in humans. Their results demonstrated the removal of all unwanted cells.
“Not only did our strategy prevent the formation of tumors, but also eliminated them completely when we switched on the suicide genes only after the tumors were fully grown,” said lead study author Juan Dominguez-Bendala, Ph.D., director of stem cell development for translational research and research associate professor of surgery at the Diabetes Research Institute, University of Miami Miller School of Medicine.
No other research method reported thus far offers the same degree of safety and specificity, as conventional suicide gene-based strategies bring about the destruction of the entire graft (transplant) or do not selectively expand the population of the needed cells.
While the team focused on deriving insulin-producing cells, this strategy, if clinically successful, has far-reaching applications beyond diabetes.
“By changing just one module of our suicide cassettes, we could make the strategy specific for any tissue of your choice. Our main interest is beta cells, but it could also be tailored to select for neurons, heart or liver cells, for example,” explained Dr. Dominguez-Bendala.
In type 1 diabetes, the insulin-producing islets cells of the pancreas have been mistakenly destroyed by the immune system, requiring patients to manage their blood sugar levels through a daily regimen of insulin therapy. Islet transplantation has restored natural insulin production in people with type 1 diabetes, as DRI scientists have published, but there are not enough cells to treat the millions of patients who can benefit. Addressing the shortage of insulin-producing cells would address one of the major challenges that stand in the way of a biological cure for the disease.
Stem cells harboring a set of suicide genes have several paths ahead of them: First, they can stop dividing and become any non-beta cell of the body. For instance, muscle, blood or bone. A second alternative is to keep dividing and form a tumor (teratoma). The third option is to become insulin-producing beta cells. Thanks to the introduced genetic modification, the first two paths bring about the destruction of any cell that takes them. Only those who “choose” the right path (i.e., pancreatic beta cells) survive.
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About the Diabetes Research Institute
The Diabetes Research Institute at the University of Miami Miller School of Medicine leads the world in cure-focused research. As one of the largest and most comprehensive research centers dedicated to curing diabetes, the DRI is aggressively working to develop a biological cure by restoring natural insulin production and normalizing blood sugar levels without imposing other risks. Researchers have already shown that transplanted islet cells allow patients to live without the need for insulin therapy. Some study participants have maintained insulin independence for more than 10 years. The DRI is now building upon these promising outcomes through its BioHub strategy, a multidisciplinary, three-pronged approach for addressing the major challenges that stand in the way of a cure: eliminate the need for anti-rejection drugs, reset the immune system to block autoimmunity, and develop an unlimited supply of insulin-producing cells. For more information, please visit DiabetesResearch.org, call 800-321-3437, or Tweet @Diabetes_DRI.
The research projects that comprise this study receive philanthropic support from the Diabetes Research Institute Foundation (DRIF). Funding was also provided by JDRF (grant number 5-2006-392).
03-23-2019 07:40 AM
A major grant has been awarded to a US researcher who will further investigate stem cell therapies for type 1 diabetes treatments.
Xiaojun "Lance" Lian, assistant professor of biomedical engineering at Penn State University, is one of three recipients of the College of Engineering's ENGineering for Innovation &Entrepreneurship (ENGINE) grant.
Now in its fifth year, ENGINE grants provide financial support to early-stage research results through a proof-of-concept phase.
Professor Lian and his team have already exploring making functional beta cells from stem cells. But there are hurdles, and transplanting beta cells does not always work.
One of the key issues is the lack of robust cell culture systems that enable stem cells to be differentiated into beta cells.
Prof Lian has developed a method which he believes may address this problem. He said: "Our new method is an improvement on previous growth-factor dependent methods, which use proteins to stimulate differentiation. This is due to small molecules being more stable, easy and cheap to manufacture, thus making stem cell differentiation more efficient and cost-effective."
Lian and colleagues plan to use the grant money to recruit students to test the new differentiation kits, which will then be shipped to other researchers for further testing.
"Completion of this project will hopefully yield two stem-cell-differentiation kits, which would have immediate potential for broad commercial impact on the treatment of type 1 diabetes."
A committee of internal and external experts in technology reviewed all applicants for the grant.
Earlier this year, scientists from the University of California San Francisco (UCSF) made a breakthrough by turning stem cells into insulin-producing cells for the first time without the need for subsequent immunosuppressant drugs.
03-23-2019 07:41 AM
Healthy fats improve nerve function in obese mice
Data support further investigation of diets rich in monounsaturated fats as potential treatment for common diabetes complication
March 18, 2019
Society for Neuroscience
Swapping dietary saturated fats for monounsaturated fats reverses nerve damage and restores nerve function in male mice, finds new preclinical research. These data support further investigation of diets rich in healthy fats as a potential treatment for the nerve damage that occurs with diabetes, known as diabetic neuropathy.
Swapping dietary saturated fats for monounsaturated fats reverses nerve damage and restores nerve function in male mice, finds new preclinical research published in JNeurosci. These data support further investigation of diets rich in healthy fats as a potential treatment for the nerve damage that occurs with diabetes, known as diabetic neuropathy.
Type 2 diabetes is associated with high-fat diets characterized by large amounts of saturated fats. In contrast, monounsaturated fatty acid-rich diets have been shown to have health benefits. Professor Eva Feldman and colleagues at the University of Michigan investigated how these two types of fats affect the progression of diabetic neuropathy, the most common complication of diabetes.
The researchers found switching mice from a saturated fat-based diet to a diet rich in monounsaturated fats derived from sunflower oil restored and protected nerve function in obese mice. Studying the beneficial effects of monounsaturated fats in sensory dorsal root ganglion neurons showed the intervention helped the cells maintain normal energy production.
These results suggest that interventions targeting dietary fats may provide a new therapeutic avenue for the treatment of diabetic neuropathy.
Materials provided by Society for Neuroscience. Note: Content may be edited for style and length.
03-23-2019 10:51 AM
It has become tedious after many years of watching research and new drugs shot down by the FDA. Sometimes, I feel skeptical that there ever will be a cure when the price of insulin generates so much revenue for drug companies...
03-23-2019 04:47 PM
03-24-2019 05:34 AM
NEW ORLEANS—Simplifying medication regimens and tailoring glycemic targets in older adults with diabetes improves adherence and avoids treatment-related complications, according to a Clinical Practice Guideline issued today by the Endocrine Society. The Society debuted the guideline during a press conference on the opening day of ENDO 2019, its annual meeting in New Orleans, La.
The guideline, titled “Treatment of Diabetes in Older Adults: An Endocrine Society Clinical Practice Guideline,” was published online and will appear in the May 2019 print issue of The Journal of Clinical Endocrinology & Metabolism (JCEM), a publication of the Endocrine Society. The guideline focuses on treatment strategies that take into consideration the overall health and quality of life of older adults with diabetes, defined as age 65 or older.
Aging plays a major role in the development of diabetes, which currently affects an estimated 33 percent of older adults in the U.S. Older adults with diabetes often have one or more co-existing conditions such as cognitive impairment, cardiovascular disease, impaired vision, and rheumatoid arthritis, which affect diabetes self-management. “The guideline encourages clinicians to consider available evidence and a patient’s overall health, likelihood to benefit from interventions and personal values when considering treatment goals such as glucose, blood pressure, and cholesterol,” said Derek LeRoith, M.D., Ph.D., of Mount Sinai School of Medicine in New York, N.Y. LeRoith chaired the writing committee that developed the guideline. “Our framework prioritizes blood glucose targets over the hemoglobin A1c test when managing diabetes in older adults.”
Recommendations from the guideline include:
Other members of the Endocrine Society writing committee that developed this guideline include: Geert Jan Biessels of the University Medical Center Utrecht in Utrecht, Netherlands; Susan S. Braithwaite of Presence Saint Francis Hospital in Evanston, Ill. and Presence Saint Joseph Hospital in Chicago, Ill.; Felipe F. Casanueva of Complejo Hospitalario Universitario de Santiago (CHUS), CIBER de Fisiopatologia Obesidad y Nutricion (CIBERobn), Instituto Salud Carlos III in Santiago de Compostela, Spain; Boris Draznin of the University of Colorado Denver Anschutz Medical Campus in Aurora, Colo.; Jeffrey B. Halter of the University of Michigan in Ann Arbor, Mich. and the National University of Singapore; Irl B. Hirsch of the University of Washington Medical Center-Roosevelt in Seattle, Wash.; Marie E. McDonnell of Brigham and Women’s Hospital and Harvard Medical School in Boston, Mass.; Mark E. Molitch of Northwestern University Feinberg School of Medicine in Chicago, Ill.; M. Hassan Murad of the Mayo Clinic, Division of Preventive Medicine in Rochester, Minn.; and Alan J. Sinclair of King’s College in London, United Kingdom.
The Society established its Clinical Practice Guideline Program to provide endocrinologists and other clinicians with evidence-based recommendations in the diagnosis, treatment, and management of endocrine-related conditions. Each guideline is developed by a writing committee of topic-related experts in the field. Writing committees rely on evidence-based reviews of the literature in the development of guideline recommendations. The Endocrine Society does not solicit or accept corporate support for its guidelines. All Clinical Practice Guidelines are supported entirely by Society funds.
This Clinical Practice Guideline was co-sponsored by The European Society of Endocrinology, The Gerontological Society of America and The Obesity Society.
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Endocrinologists are at the core of solving the most pressing health problems of our time, from diabetes and obesity to infertility, bone health, and hormone-related cancers. The Endocrine Society is the world’s oldest and largest organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions.
The Society has more than 18,000 members, including scientists, physicians, educators, nurses and students in 122 countries
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