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Steroid originally discovered in the dogfish shark attacks Parkinson’s-related toxin in animal model

Credit: Doug Costa, NOAA/SBNMS MEDIA CONTACT: Karen Teber WASHINGTON (January 16, 2017) — A synthesized steroid mirroring one naturally made by the dogfish shark prevents the buildup of a lethal protein implicated in some neurodegenerative diseases, reports an international research team studying an animal model of Parkinson’s disease. The clustering of this protein, alpha-synuclein (α-synuclein), is the hallmark of Parkinson’s and dementia with Lewy bodies, suggesting a new potential compound for therapeutic research. The finding, published online today in Proceedings of the National Academy of Sciences, also demonstrated that the synthesized steroid, called squalamine, reduced the toxicity of α-synuclein clumps that already existed. The pre-clinical study results show that squalamine prevents and eliminates α-synuclein build up inside neurons by unsticking the protein from the inner wall of nerve cells, where it clings and builds up into toxic clumps, researchers say. The animal model used for this study, C. elegans, is a nematode worm genetically engineered to produce human α-synuclein in its muscles. As these worms age, α-synuclein builds up within their muscle cells causing cell damage and paralysis. “We could literally see that squalamine, given orally to the worms, did not allow α-synuclein to cluster, and prevented muscular paralysis inside the worms,” says the study’s co-senior author, Michael Zasloff, MD, PhD, professor of surgery and pediatrics at Georgetown University School of Medicine and scientific director of the MedStar Georgetown Transplant Institute. The study’s lead author, graduate student Michele Perni, and other co-senior authors, Michele Vendruscolo, PhD and Christopher M. Dobson, DPhil, ScD, are from Cambridge University. An additional co-senior author, Adriaan Bax, PhD, is from National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health (NIH) in Bethesda, Maryland. Scientists [...]

Improving the longevity of functionally integrated stem cells in regenerative vision therapy

Buck scientists restore long-term vision in blind mice, making a case for addressing the immune system’s role in rejecting transplanted cells January 12, 2017/Novato, California:  Stem cell therapies hold great promise for restoring function in a variety of degenerative conditions, but one of the logistical hurdles is how to ensure the cells survive in the body long enough to work. Researchers from the Buck Institute report one of the first demonstrations of long-term vision restoration in blind mice by transplanting photoreceptors derived from human stem cells and blocking the immune response that causes transplanted cells to be rejected by the recipient. Publishing in the Cell Stem Cell, this work highlights immune system rejection as one of the key issues that needs to be addressed to improve efficiency of stem cell regeneration therapies. The findings support a path to improving clinical applications, specifically for restoring vision in humans by allowing photoreceptors derived from human stem cells to integrate and thrive in the eye. “This turned into a nice story of long-term restoration of vision in completely blind mice,” said Buck faculty and senior author Deepak Lamba, PhD, MBBS. “We show that these mice can now perceive light as far out as 9-months following injection of these cells.” Photoreceptors are specialized neurons in the retina that convert light into signals that the brain interprets as sight. Loss of these cells is a common endpoint in degenerative eye diseases. Human embryonic stem cells can provide a potential source for photoreceptor replacement, but despite Lamba’s prior work showing that photoreceptors derived from stem cells could function in mice, researchers   hadn’t been able to show long-term sustained vision restoration. A major controversy in field, said Lamba, was whether the transplanted [...]

Researchers use stem cells to regenerate the external layer of a human heart

By Stefanie Tomlinson January 11, 2017 UNIVERSITY PARK, Pa. — A process using human stem cells can generate the cells that cover the external surface of a human heart — epicardium cells — according to a multidisciplinary team of researchers. "In 2012, we discovered that if we treated human stem cells with chemicals that sequentially activate and inhibit Wnt signaling pathway, they become myocardium muscle cells," said Xiaojun Lance Lian, assistant professor of biomedical engineering and biology, who is leading the study at Penn State. Myocardium, the middle of the heart’s three layers, is the thick, muscular part that contracts to drive blood through the body. The Wnt signaling pathway is a group of signal transduction pathways made of proteins that pass signals into a cell using cell-surface receptors. "We needed to provide the cardiac progenitor cells with additional information in order for them to generate into epicardium cells, but prior to this study, we didn't know what that information was," said Lian. "Now, we know that if we activate the cells' Wnt signaling pathway again, we can re-drive these cardiac progenitor cells to become epicardium cells, instead of myocardium cells." The group's results, published in Nature Biomedical Engineering, bring them one step closer to regenerating an entire heart wall. Through morphological assessment and functional assay, the researchers found that the generated epicardium cells were similar to epicardium cells in living humans and those grown in the laboratory. "The last piece is turning cardiac progenitor cells to endocardium cells (the heart's inner layer), and we are making progress on that," said Lian. The group's method of generating epicardium cells could be useful in clinical applications, for patients who suffer a heart attack. According to the [...]

Bionic pancreas treats adults with type 1 diabetes

January 10, 2017 At a Glance A bionic pancreas system improved blood glucose control in adults with type 1 diabetes better than conventional insulin pump therapy. Larger and longer studies will be needed to further assess the benefits and risks of the automated system. The bionic pancreas system includes a continuous glucose monitor and a smart phone app that wirelessly connects with insulin and glucagon pumps. Patents for the system have been licensed to Beta Bionics. Raj Setty, Boston University Diabetes is a disorder in blood glucose levels. Glucose is a sugar that serves as fuel for the body. When blood glucose levels rise, beta cells in the pancreas normally make and secrete the hormone insulin, which triggers cells throughout the body to take up sugar from the blood. In type 1 diabetes, the body’s own immune system attacks and destroys beta cells. People with type 1 diabetes thus need to take insulin to maintain blood glucose levels within a certain range to prevent life-threatening complications. Current treatments for type 1 diabetes include carbohydrate counting, careful monitoring of blood glucose, and adjusting insulin dosing in response. A research team led by Drs. Steven J. Russell of Massachusetts General Hospital and Edward R. Damiano and Firas El-Khatib of Boston University developed and tested a bionic pancreas. The system consists of a smart phone that wirelessly communicates with 2 pumps. The pumps deliver either insulin or glucagon (a hormone that increases blood glucose levels) through tubing that goes under the skin. The hormones are administered based on readings provided to the smart phone every 5 minutes from a continuous glucose monitor. In previous short-term studies, the scientists showed that the device could maintain blood glucose levels close [...]

Unraveling autism

A multifaceted approach aims to detect, treat and even reverse the disorder. BY REBECCA BOYLE, January 3, 2017 Washington University in St. Louis - Like many patients visiting a doctor’s office, Kim Sebenoler started out her appointment by heading to the nearest restroom to give a urine sample. But her visit to the lab of John Constantino, MD, director of the William Greenleaf Eliot Division of Child Psychiatry, was not a typical exam. The goal was not to measure proteins in her urine or check her overall wellness. Instead, researchers took her urine cells to replicate human brain cell function in a Petri dish. The study is one of three major approaches School of Medicine researchers are using to unravel the physical and psychological underpinnings of autism. The unique, multifaceted effort — studying genes, brain activity patterns and behavior — is giving researchers and practitioners a better understanding of the disorder, which today affects one in every 100 Americans. The cells are helping co-investigators Constantino and neuroscientist Azad Bonni, MD, PhD, explore how brain function changes in people with autism spectrum disorder (ASD). Both researchers are international leaders — Constantino in clinical autism studies and Bonni in advancing understanding of the underlying mechanisms of brain development. The Kroll lab has figured out not only how to create neurons, but also to create neuron types that perform specific functions. These types — cortical excitatory neurons and inhibitory neurons — often are abnormal in patients with autism. This process includes a specific chemical treatment to generate these types of neurons in a Petri dish. In this case, populations of neurons are derived from the cells of the Sebenoler family. The Kroll lab has figured out not only [...]

Researchers Investigate New Treatments for Leading Cancers

WASHINGTON — January 02, 2017 12:56 AM Carol Pearson Scientists are investigating new ways of treating people with liver cancer. The methods range from developing an artificial liver, to seeing if genetically-modified pigs can produce organs compatible with humans. For those who have liver cancer, their only cure lies in a liver transplant or removal of the cancerous part of the organ. Both require major surgery. And, patients who get a transplant will need to take immuno-suppressant drugs for the rest of their lives. However, scientists are working on a new approach that is minimally invasive. With both chemotherapy and radiation, healthy cells around the tumor are damaged. But this approach involves the use of natural, non-toxic chemical compounds from plants. Kattesh Katti, a professor at the University of Missouri School of Medicine, led a study that used nanotechnology to target and destroy precancerous tumor cells in the livers of mice and in in-vitro human cells. “It sounds like a fairy tale, but we are really in advanced stages in terms of tumor treatment, in terms of disease diagnostics," said Katti. Katti's work involved very small particles of gold encapsulated in a protective stabilizer from an acacia tree. The particles attract precancerous and malignant cells, which are far more susceptible to lower levels of heat than healthy cells. “The patient will be administered with these nano particles. Within a couple of hours, the patient will be treated with lasers, and then the patient can go home. So, there is no radioactivity. There is no toxic waste. There is no toxicity, systemic toxicity, to the patient,” said Katti. Katti said the cost of treatment will be low because one gram of gold can be used to treat 50 [...]

New Drug Could Help Prevent Artery Disease in High-risk Patients

A recent study by researchers at the University of Missouri School of Medicine has shown that a protein inhibitor drug prevents these blockages, and could be a new therapeutic approach to prevent heart attack, stroke and other diseases caused by blocked blood vessels. Dec. 21, 2016- According to the American Heart Association, approximately 2,200 Americans die each day from heart attacks, strokes and other cardiovascular diseases. The most common cause is blocked blood vessels that can no longer supply oxygen and nutrients to the heart and brain. A recent study by researchers at the University of Missouri School of Medicine has shown that a protein inhibitor drug prevents these blockages, and could be a new therapeutic approach to prevent heart attack, stroke and other diseases caused by blocked blood vessels. William Fay, MD "Arteries are living hoses that narrow and enlarge in order to regulate blood flow to organs and muscles," said William Fay, MD, the J.W. and Lois Winifred Stafford Distinguished Chair in Diabetes and Cardiovascular Research at the MU School of Medicine and senior author of the study. "Smooth muscle cells in the artery regulate blood flow by constricting and relaxing. However, when chronic inflammation occurs in a blood vessel - typically in response to diabetes, high cholesterol and cigarette smoking - the smooth muscle cells in the walls of arteries change their behavior. They gradually accumulate inside the artery and narrow the blood vessel. In the case of coronary arteries, which supply blood to heart muscle cells, this process produces blockages that can lead to a heart attack." Plasminogen activator inhibitor-1, or PAI-1, is a naturally occurring protein within blood vessels that controls cell migration. With diseases such as diabetes and obesity, [...]

Landmark Alzheimer’s prevention trial to evaluate third drug

Effort to study drug's ability to prevent, delay the disease By Tamara Bhandari December 19, 2016 Washington University School of Medicine's Randall J. Bateman, MD, talks with DIAN-TU trial participant Natalie Shriver, of Omaha, about a study to test drugs that may prevent or delay Alzheimer's disease. (Photo: Robert Boston/Washington University School of Medicine) An international team led by Washington University School of Medicine in St. Louis has selected a third investigational drug to be tested in a worldwide clinical trial — already underway — aimed at finding treatments to prevent Alzheimer’s disease. The third drug is being developed by Janssen Research & Development, LLC, in New Jersey. It is designed to lower production of amyloid beta, a protein that clumps together into plaques and damages neurons in the brain, leading to memory loss, cognitive problems and confusion. The drug is designed to block the enzyme beta secretase — which produces amyloid beta — with a goal of reducing the amount of amyloid beta available to clump and cause neurodegeneration. This investigational drug joins two others already being evaluated in the Dominantly Inherited Alzheimer’s Network Trial Unit (DIAN-TU) study, which involves people with an inherited predisposition to develop Alzheimer’s at a young age, usually in their 30s, 40s or 50s. Participants already enrolled will continue on their existing drug regimens, and additional volunteers with no or mild symptoms of cognitive impairment will be enrolled to evaluate the third drug. “We are delighted with the new collaboration with Janssen Research & Development to expand the number of novel therapeutic targets we are testing,” said Washington University Alzheimer’s specialist Randall J. Bateman, MD, director of the DIAN-TU, a public-private-philanthropic research partnership. “Testing a beta secretase inhibitor in [...]

Experimental implant shows promise for restoring voluntary movement after spinal cord injury

UCLA scientists test electrical stimulation that bypasses injury; technique boosts patient’s finger control, grip strength up to 300 percent Elaine Schmidt | December 13, 2016 Aspinal stimulator being tested by doctors at Ronald Reagan UCLA Medical Center is showing promise in restoring hand strength and movement to a California man who broke his neck in a dirt bike accident five years ago. In June, Brian Gomez, now 28, became one of the first people in the world to undergo surgery for the experimental device. UCLA scientists inserted the 32-electrode stimulator below the site of Gomez’s spinal cord injury, near the C-5 vertebrae in the middle of his neck. That’s the area most commonly associated with quadriplegia, the loss of function and feeling in all four limbs. “The spinal cord contains alternate pathways that it can use to bypass the injury and get messages from the brain to the limbs,” said Dr. Daniel Lu, an associate professor of neurosurgery at the David Geffen School of Medicine at UCLA and director of the school’s Neuroplasticity and Repair Laboratory. “Electrical stimulation trains the spinal cord to find and use these pathways.” Although other devices have shown promise recently for treating paralysis, they were either tested in animals or relied on robotic limbs. The approach used by the UCLA doctors is unique because it is designed to boost patients’ abilities to move their own hands, and because the device is implanted in the spine instead of the brain. The technique essentially gets the nerve signal to behave like a driver who avoids rush-hour traffic by taking side streets instead of a busy highway. “If there is an accident on the freeway, traffic comes to a standstill, but there are [...]

Cellular immunotherapy targets a common human cancer mutation

December 7, 2016 In a study of an immune therapy for colorectal cancer that involved a single patient, a team of researchers at the National Cancer Institute (NCI) identified a method for targeting the cancer-causing protein produced by a mutant form of the KRAS gene. This targeted immunotherapy led to cancer regression in the patient in the study. The finding appeared Dec. 8, 2016, in the New England Journal of Medicine. The study was led by Steven A. Rosenberg, M.D., Ph.D., chief of the Surgery Branch at NCI’s Center for Cancer Research, and was conducted at the NIH Clinical Center. NCI is part of the National Institutes of Health. More than 30 percent of all human cancers are driven by mutations in a family of genes known collectively as RAS, which has three members: KRAS, NRAS, and HRAS. Mutations in the KRAS gene are thought to drive 95 percent of all pancreatic cancers and 45 percent of all colorectal cancers. A mutation called G12D is the most common KRAS mutation and is estimated to occur in more than 50,000 new cases of cancer in the United States each year. Because of their importance in cancer causation, worldwide efforts to successfully target mutant RAS genes are being pursued. Such efforts have met with limited success to date. In attempting to develop more effective approaches to targeting RAS, Rosenberg’s team isolated tumor infiltrating lymphocytes (TILs) that targeted the KRAS G12D mutation from tumor nodules in the patient’s lungs that developed after colorectal cancer cells had spread to the lungs. TILs are white blood cells that migrate from the bloodstream into a tumor. The isolated TILs were grown in the laboratory to large numbers and then infused into [...]