Syndicate content

Archive

Nasal Vaccine Shows Promise for Alzheimer’s, Stroke

Researchers led by Dr. Dan Frenkel of Tel Aviv University's Department of Neurobiology are working on a nasally-delivered 2-in-1 vaccine that promises to protect against both Alzheimer's and stroke. The new vaccine repairs vascular damage in the brain by rounding up "troops" from the body's own immune system. And in addition to its prophylactic effect, study results suggest that the vaccine can have beneficial effects even when Alzheimer's symptoms are already present. The research on this new technology was recently accepted for publication in the journal Neurobiology of Aging. "Using part of a drug that was previously tested as an influenza drug, we've managed to successfully induce an immune response against amyloid proteins in the blood vessels," said Dr. Frenkel, who collaborated on this project with Professor Howard L. Weiner of Brigham and Women's Hospital, Harvard Medical School. "In early pre-clinical studies, we've found it can prevent both brain tissue damage and restore cognitive impairment," Dr. Frenkel added. Modifying a vaccine technology owned by Glaxo Smith Kline, a multinational drug company, Tel Aviv University's new therapeutic approach activates a natural mechanism in our bodies that fights against vascular damage in the brain. The vaccine, Dr. Frenkel explained, activates macrophages — phagocytic cells in the body that swallow foreign antigens. When the vaccine activates large numbers of these macrophages, they clear away the damaging build-up of waxy amyloid proteins in the brain's vascular system. Studies in animal models showed that once these proteins are cleared from the brain, further damage can be prevented, and existing damage due to a previous stroke can be repaired.

Two Genes for "Binge Drinking" Identified

Scientists at the University of Maryland Medical School and the Medical University Vienna have identified two genes associated with binge drinking, a discovery that may pave the way toward new, more effective treatments of excessive alcohol consumption. The scientists found that manipulating two receptors in the brain, GABA receptors and toll-like receptor 4 (TLR4), "caused profound reduction" of binge drinking for two weeks in rodents that had been bred and trained to drink excessively. About 30 percent of Americans who drink do so excessively, and about 75,000 people die each year from the effects of excessive drinking. Current treatments for excessive alcohol drinking include prescription drugs Revia and Campral for controlling cravings. To ease withdrawal symptoms, doctors often prescribe medications such as Valium and Librium that carry their own risks of addiction. Valium and Librium reduce the anxiety alcoholics feel when they stop drinking but do not reduce cravings for alcohol. The new study found that treatments that manipulate both the GABA receptor and TLR4 have the potential to reduce anxiety and control cravings, with little to no risk for addiction, according to lead investigator Dr. Harry June, professor of psychiatry and pharmacology and experimental therapeutics at the University of Maryland School of Medicine.

February 28th

Stem Cell Study Shows Link Between Rare Lung Disease and Blood Cell Abnormalities

Results from a recent study have revealed a close relationship between pulmonary arterial hypertension (PAH)—a rare and deadly disease characterized by exceedingly high blood pressure in the arteries carrying blood from the heart to the lungs—and abnormalities of the blood-forming cells in the bone marrow (known as myeloid abnormalities). The study, which was conducted by a team of researchers at the Cleveland Clinic and Vanderbilt University, showed that blood progenitor cells (cells that are capable of forming white blood cells, red blood cells, or platelets in the bone marrow and are reported to affect blood vessel formation), are increased in the bone marrow, blood, and lungs of patients with PAH. These findings suggest that the disease processes in the bone marrow and the lungs are related. “This research pieces together a number of previous studies and observations suggesting a very close relationship between PAH and underlying bone marrow abnormalities,” said Dr. Serpil Erzurum, a co-author of the study and Chair of the Department of Pathobiology at the Cleveland Clinic. “Our study honed in on the stem cells involved in blood vessel maintenance to identify factors that might be involved in bone marrow stem cell abnormalities as well as progressive arterial disease.”

Compound Studied in Birth Defects May Be Useful Against Cancer

A compound being studied in the investigation of intestinal birth defects may prove useful in fighting cancer, according to the results of a recent study published in the February 25 issue of Chemistry & Biology. During the screening of chemical compounds created by North Carolina State chemist Dr. Alex Deiters, developmental biologist Dr. Nanette Nascone-Yoder found one of particular interest to her research: a compound that induced heterotaxia, a disordering or mirror-image “flipping” of internal organs, in the frog embryos she was studying. Dr. Nascone-Yoder is particularly interested in the genetic processes involved in proper formation of the gut tube, which later becomes the intestinal tract. “For the intestinal tract to form properly, it has to develop asymmetrically. This compound disrupts asymmetry, so it could be quite useful in helping us to determine when and where intestinal development goes wrong in embryos,” Dr. Nascone-Yoder said. But the compound, dubbed “heterotaxin” by the researchers, had effects beyond just inducing heterotaxia. “We also noticed that the compound prevents normal blood-vessel formation and prevents cells from migrating by increasing cellular adhesion – basically, the cells are stuck together and can’t move.”

April 6th, 2010

Phase 3 Trial for Promising Melanoma Vaccine

Rush University Medical Center in Chicago is leading a nationwide phase 3 clinical trial to determine whether a promising vaccine for advanced melanoma can effectively treat the deadly skin cancer. An earlier phase 2 trial of the experimental drug involving 50 patients with metastatic melanoma had what were referred to as “stunning results.” Eight patients recovered completely and four partially responded to the vaccine, according to the researchers. "Very few treatment options exist for patients with advanced melanoma, none of them satisfactory, which is why oncologists are so excited about the results we found in our phase 2 study," said Dr. Howard Kaufman, associate dean of Rush Medical College and director of the Rush Cancer Program. Dr. Kaufman is leading the phase 3 study. The vaccine being tested is called OncoVEX, initially developed to combat herpes virus. Researchers discovered accidentally that the vaccine attacked cancerous tissue when it was inadvertently placed in a Petri dish of tumor cells. The vaccine includes an oncolytic virus, a reprogrammed virus that has been converted into a cancer-fighting agent that attacks tumor cells while leaving healthy cells undamaged. OncoVEX also carries biological agents that boost the immune response to melanoma. The vaccine is injected directly into lesions that can be felt or seen, with or without ultrasound. The procedure is generally done in a physician's office. "What really surprised, and encouraged, us was that the vaccine worked not just on the cells we injected, but on lesions in other parts of the body that we couldn't reach," Dr. Kaufman said in commenting on the phase 2 results. "In other words, the vaccine prompted an immune response that was circulated through the bloodstream to distant sites.

April 5th

Vascularization Pathway Mediated by MicroRNA Is Discovered

Researchers at the University of Massachusetts Medical School and colleagues have discovered a critical step for blood vessel growth in zebrafish embryos, providing new insight into how vascular systems develop and offering a potential therapeutic target for preventing tumor growth, which depends on vascularization. The researchers have identified a novel microRNA-mediated genetic pathway responsible for new blood vessel growth (angiogenesis) in zebrafish embryos. The work provides new insights into how vascular systems use the forces of existing blood flow to initiate the growth of new vessels. Focusing on the development of the fifth and sixth aortic arches in the zebrafish, senior author Dr. Nathan Lawson described how the forces exerted by blood flow on endothelial cells are a critical component for expressing a microRNA that triggers new vessel development. In the early stages of development, when blood flow is present in the aortic vessels, but the vascular linkages between the two arches have yet to be established, the stimulus provided by active blood flow leads to expression of an endothelial-cell specific microRNA (mir-126). In turn, this microRNA turns on vascular endothelial growth factor (VEGF), a chemical signal produced by surrounding cells that normally stimulates angiogenesis. Thus, blood flow allows the endothelial cells to respond to VEGF by growing into new blood vessels. However, when blood flow in the aortic arches was restricted, mir-126 failed to be expressed. In the absence of this microRNA, new blood vessels were unable to develop due to a block in VEGF signaling. "We have known for over a hundred years that blood flow makes new vessels grow," said Dr. Lawson. "But we never really knew how cells in a growing vessel interpreted this signal.

Pancreas Alpha-Cells Can Convert to Insulin-Producing Beta-Cells

In a mouse model, scientists have discovered that alpha-cells in the pancreas, which do not produce insulin, can convert into insulin-producing beta-cells, advancing the prospect of regenerating beta-cells as a cure for type 1 diabetes. The research team, led by senior author Dr. Pedro L. Herrera of the University of Geneva, demonstrated that beta-cells will spontaneously regenerate after near-total beta-cell destruction in mice and the majority of the regenerated beta-cells are derived from alpha-cells that had been reprogrammed, or converted, into beta-cells. Using a unique model of diabetes in mice, in which nearly all of the beta-cells are rapidly destroyed, the researchers found that if the mice were maintained on insulin therapy, beta-cells were slowly and spontaneously restored, eventually eliminating the need for insulin replacement. Alpha-cells normally reside alongside beta-cells in the pancreas and secrete a hormone called glucagon, which works in opposition to insulin to regulate the levels of sugar in the blood. Alpha-cells are not attacked by the autoimmune processes that destroy beta-cells and cause type 1 diabetes. Dr. Andrew Rakeman, the Juvenile Diabetes Research Foundation (JDRF) Program Manager in Beta-Cell Therapies and who was not involved in the research, said that the breakthrough in Dr. Herrera's work is the demonstration that alpha-to-beta-cell reprogramming can be a natural, spontaneous process. "If we can understand the signals that are triggering this conversion, it will open a whole new potential strategy for regenerating beta-cells in people with type 1 diabetes," he said. "It appears that the body can restore beta-cell function either through reprogramming alpha-cells to become beta-cells or, as previously shown by others, by increasing growth of existing beta cells.

April 4th

Upcoming Personalized Medicine 3.0 Conference—Targeting Cancer

“Personalized Medicine 3.0--Targeting Cancer” is a one-day conference and networking opportunity for health and industry professionals, educators, and scientists. The conference will focus on cancer--using genomic information to characterize tumors precisely and ensure the use of the most effective treatment regimens for individual patients with the fewest side effects. The organizers note that personalized medicine is poised to transform healthcare over the next several decades, and that it offers both the possibility of improved health outcomes and the potential to make healthcare more cost-effective. The conference will be held in San Francisco at San Francisco State University from 9 am to 7 pm on Tuesday, May 25, 2010. The two previous annual conferences on personalized medicine have been enormous successes and similar results are expected for this third conference. The organizers urge you to register early as space is limited and the registration fee is $249 until April 15, 2010. Registration includes a light breakfast, lunch, and a networking reception at the end of the day. Registration details and a preliminary program are available at the conference web site (http://personalizedmedicine.sfsu.edu/), as are additional details on the conference.

New Genetic Risk Factors Identified for Brain Aneurysms

In the largest genome-wide study of brain aneurysms ever conducted, an international team led by researchers at the Yale School of Medicine has identified three new genetic variants that increase a person's risk for developing this deadly disease. "These findings provide important new insights into the causes of intracranial aneurysms and are a critical step forward in the development of a diagnostic test that can identify people at high risk prior to the emergence of symptoms," said Dr. Murat Gunel, senior author of the report. "Given the often-devastating consequences of the bleeding in the brain, early detection can be the difference between life and death." The new study, the second by Yale researchers published within the last 15 months, brings to five the number of regions of the genome that have been found to contribute to the nearly 500,000 cases of this devastating disorder diagnosed annually worldwide. The researchers searched across the entire genome for changes in the genetic code that were shared more often by aneurysm patients than by unaffected individuals. The researchers determined that if persons carry all of the risk variants discovered by the Yale-led team, they are five to seven times more likely to suffer an aneurysm than those individuals who carry none. While these findings have transformed the understanding of the genetic risks for intracranial aneurysms, considerable work remains to be done, the researchers noted. "These five findings explain about 10 percent of genetic risk of suffering an aneurysm," Dr. Gunel said. "This is 10 percent more than we understood just a couple of years ago, but there is a long way to go."

April 3rd

Second Study Suggests Life-Extending Drug May Be Effective in Alzheimer’s

A second study, in a different mouse model, has shown that the pharmacological agent rapamycin, which has previously been shown to extend life span in mice, may prevent Alzheimer’s disease in humans. A bacterial product first isolated from the soil on Easter Island, rapamycin is already approved by the U.S. Food & Drug Administration to prevent organ rejection in transplant patients. The first of the two Alzheimer’s studies, was published online on February 23, 2010 in the Journal of Biological Chemistry (A. Caccamo et al.), and showed that rapamycin curbed the effects of Alzheimer’s in one mouse model. The new study, published on April 1 in PLoS ONE, showed similar effects in a completely different mouse model of Alzheimer’s. Both reports came from the University of Texas Health Science Center at San Antonio and collaborating institutions. The second report showed that administration of rapamycin improved learning and memory in a strain of mice engineered to develop Alzheimer's. The improvements in learning and memory were detected in a water maze activity test that is designed to measure learning and spatial memory. The improvements in learning and memory correlated with lower damage in brain tissue. "Rapamycin treatment lowered levels of amyloid-beta-42, a major toxic species of molecules in Alzheimer's disease," said senior author Dr. Veronica Galvan. "These molecules, which stick to each other, are suspected to play a key role in the early memory failure of Alzheimer's."