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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 [...]

Nanotechnology a ‘green’ approach to treating liver cancer

November 29, 2016 (Nanowerk News) According to the American Cancer Society, more than 700,000 new cases of liver cancer are diagnosed worldwide each year. Currently, the only cure for the disease is to surgically remove the cancerous part of the liver or transplant the entire organ. However, an international study led by University of Missouri School of Medicine researchers has proven that a new minimally invasive approach targets and destroys precancerous tumor cells in the livers of mice and in vitro human cells (Journal of Photochemistry and Photobiology B: Biology, "Photothermal therapy mediated by gum Arabic-conjugated gold nanoparticles suppresses liver preneoplastic lesions in mice"). "The limitations when treating most forms of cancer involve collateral damage to healthy cells near tumor sites," said Kattesh Katti, Ph.D., Curators' Professor of Radiology and Physics at the MU School of Medicine and lead author of the study. "For more than a decade we have studied the use of nanotechnology to test whether targeted treatments would reduce or eliminate damage to nearby healthy cells. Of particular interest has been the use of green nanotechnology approaches pioneered here at MU that use natural chemical compounds from plants." Kattesh Katti, Ph.D., University of Missouri-Columbia The study was conducted in the United States and Egypt, and it involved the use of gold nanoparticles encapsulated by a protective stabilizer called gum Arabic. The nanoparticles were introduced to the livers of mice intravenously and were heated with a laser through a process known as photothermal therapy. "Gum Arabic is a natural gum made of the hardened sap from acacia trees," said Katti, who also serves as director of the MU Institute of Green Nanotechnology and is the Margaret Proctor Mulligan Distinguished Professor of Medical Research [...]

New topical immunotherapy effective against early skin cancer

Combination of two drugs reduces precancerous skin lesions By Julia Evangelou Strait November 21, 2016 Washington University dermatologist Lynn Cornelius, MD, (left) conducts a skin exam with patient Robert Manchester. Manchester is a participant in a clinical trial testing the effectiveness of a new topical immunotherapy against precancerous skin lesions called actinic keratosis, often found on sun-damaged skin. (Photo: Robert J. Boston/Washington University School of Medicine) A combination of two topical drugs that have been in use for years triggers a robust immune response against precancerous skin lesions, according to a new study. The research, from Washington University School of Medicine in St. Louis and Harvard Medical School, shows that the therapy activates the immune system’s T cells, which then attack the abnormal skin cells. The study, which involved patients with actinic keratosis, a precursor to a type of skin cancer called squamous cell carcinoma, is published Nov. 21 in The Journal of Clinical Investigation. “We looked at precancerous lesions on patients with sun-damaged skin,” said Washington University dermatologist and study co-author Lynn A. Cornelius, MD, director of the Division of Dermatology. “Most commonly found on the face, scalp and arms, these lesions appear abnormal by visual examination and under the microscope but are not full-blown skin cancers. But because these lesions have the potential to develop into a true skin cancer, they are commonly treated. Our study shows this combination therapy is more effective and better tolerated than current treatment practices.” On average, the investigational therapy reduced the number of precancerous skin lesions on the face by almost 88 percent compared with a 26 percent reduction using the standard chemotherapy. While some side effects such as skin scaling and itching were similar with both [...]

Researchers launch first clinical trial for Wolfram syndrome

Many people with rare genetic disease die prematurely by Jim Dryden•November 10, 2016 The drug dantrolene is a muscle relaxant approved to treat patients with cerebral palsy, multiple sclerosis and muscle spasticity. Recent research also suggests it can prevent the destruction of insulin-secreting beta cells in animal models of Wolfram syndrome. Researchers at Washington University School of Medicine in St. Louis are launching a new clinical trial to assess the safety of a drug treatment for patients with the rare disease Wolfram syndrome. Wolfram syndrome affects about one in every 500,000 people worldwide. Many of those patients die prematurely from the disease. Patients with Wolfram syndrome typically develop diabetes at a very young age and require insulin injections several times each day. The disorder also causes hearing loss, vision problems and difficulty with balance. Although doctors treat patients’ symptoms, there have not been any therapies that slow the syndrome’s progress. However, researchers at Washington University School of Medicine soon will test a drug treatment in 24 patients who have the genetic disorder. The scientists previously reported in the Proceedings of the National Academy of Sciences that the drug, dantrolene — a muscle relaxant approved to treat patients with cerebral palsy, multiple sclerosis and muscle spasticity — prevents the destruction of insulin-secreting beta cells in animal models of Wolfram syndrome and in brain cells differentiated from skin samples taken from patients with the illness. “Nobody has ever tested dantrolene in patients with Wolfram syndrome, so our first and most important objective is to make sure it’s safe,” said principal investigator Fumihiko Urano, MD, PhD, the Samuel E. Schechter Professor of Medicine. “I am very hopeful, however. The major question that I get from every patient I [...]

Changing cell behavior could boost biofuels, medicine

By Beth Miller November 7, 2016 An engineer at Washington University in St. Louis developed an algorithm that suggests gene to remove from certain cells, such as yeast, to get them to perform a normal activity in a different environment or situation. A computer scientist at Washington University in St. Louis has developed a way to coax cells to do natural things under unnatural circumstances, which could be useful for stem cell research, gene therapy and biofuel production. Brent Michael Brent, the Henry Edwin Sever Professor of Engineering in the School of Engineering & Applied Science, has designed an algorithm, called NetSurgeon, that recommends genes to surgically remove from a cell’s genome to force it to perform a normal activity in a different environment or circumstance. For example, ordinary baker’s yeast cells normally produce a lot of alcohol, a biofuel, when fed sugar extracted from the edible kernels of corn plants. NetSurgeon designed genetic surgeries that convinced the cells to make more alcohol when fed a type of sugar found in the inedible leaves and stalks. The research is published in PNAS Early Edition Oct. 31. “Yeast have been engineered to make alcohol out of xylose, a type of sugar found in the woody parts of plants, but they don’t do it very well,” Brent said. “We think the problem is not that they can’t do it, but that they don’t want to. So we have to convince them by making them use the same set of genes they use when they’re fed sugar from corn kernels. We sometimes think about this as causing the yeast to ‘hallucinate’ that they are in a sugar they like to turn into alcohol. “Ultimately, what we want to [...]

Earlier Alzheimer’s diagnosis may be possible with new imaging compound

New tool detects Alzheimer’s protein, may help identify brain changes, assess treatment effects By Tamara Bhandari November 2, 2016 Researchers at Washington University School of Medicine in St. Louis have developed a chemical compound that detects the Alzheimer’s protein amyloid beta better than current FDA-approved agents. The compound potentially may be used in brain scans to identify people in the earliest stages of Alzheimer’s disease. In the image above, the compound has passed from the bloodstream of a living mouse into its brain, where it is detected by a positron emission tomography (PET) scan. Arrows indicate clumps of amyloid beta. (Image: Ping Yan and Jin-Moo Lee) By the time unambiguous signs of memory loss and cognitive decline appear in people with Alzheimer’s disease, their brains already are significantly damaged, dotted with clumps of a destructive protein known as amyloid beta. For years, scientists have sought methods and clues to help identify brain changes associated with Alzheimer’s earlier in the disease process, so they can try to stop or even reverse the changes before they severely affect people’s lives. Now, researchers at Washington University School of Medicine in St. Louis have developed a chemical compound, named Fluselenamyl, that detects amyloid clumps better than current FDA-approved compounds. If a radioactive atom is incorporated into the compound, its location in a living brain can be monitored using positron emission tomography (PET) scans. The compound, described in a paper published Nov. 2 in Scientific Reports, one of the Nature journals, potentially could be used in brain scans to identify the signs of early-stage Alzheimer’s disease or to monitor response to treatment. “Fluselenamyl is both more sensitive and likely more specific than current agents,” said Vijay Sharma, PhD, a professor of radiology, [...]

Achilefu receives inaugural breast cancer research award

$4.5 million from U.S. defense department funds innovative light therapy October 26, 2016 ROBERT BOSTON PHOTO Samuel Achilefu, PhD, (shown) a scientist at Washington University School of Medicine in St. Louis, is the first recipient of the Breast Cancer Research Program Distinguished Investigator Award, from the U.S. Department of Defense. As part of the award, Achilefu will receive $4.5 million to support his work to use light to activate drugs and the immune system in the body. Samuel Achilefu, PhD, a scientist and inventor at Washington University School of Medicine in St. Louis, has been recognized as the first recipient of the Breast Cancer Research Program Distinguished Investigator Award, from the U.S. Department of Defense. The award comes with $4.5 million to support his innovative work to use light to activate drugs and the immune system in the body. He is developing the approach as a safer and more effective way to treat breast cancer than currently available chemotherapy drugs. So-called photoimmunotherapy also has the potential to help those with breast cancer that has spread, which typically evolves to become resistant to chemotherapy. Metastatic disease is responsible for more than 90 percent of the 41,000 breast cancer deaths in the U.S. each year. Washington University scientists led by Samuel Achilefu, PhD, have devised a way to apply light-based therapy to deep tissues never before accessible. They delivered light directly to tumor cells, in the form of an imaging agent frequently used in positron emission tomography (PET) scans. This light source, along with a novel cancer-targeting product and a chemotherapy drug, selectively kill cancer cells. “The goal is to harness the power of light and cancer-specific tumor targeting strategy to effectively treat tumors while minimizing or even eliminating damage [...]