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REGENERATIVE MEDICINE: MECHANISM THAT REGULATES THE DEVELOPMENT OF STEM CELLS INTO NEURONS IDENTIFIED
Researchers at the University of Southern California have identified a novel mechanism in the regulation and differentiation of neural stem cells. Researchers found that the protein receptor Ryk plays a key role in the differentiation of neural stem cells, and demonstrated a signaling mechanism that regulates neuronal differentiation as stem cells begin to grow into neurons. The study, published in the journal Developmental Cell, could have important implications for regenerative medicine and cancer therapies. Neural stem cells can potentially be used for cell-replacement therapy for neurodegenerative diseases such as Alzheimer’s and Parkinson’s Disease, as well as spinal cord injury, the researchers said. They believe the knowledge gained from this study will potentially help to generate neurons for such therapy. The researchers found that during neurogenesis, when neural stem cells start to grow into neurons, Ryk protein is cleaved and translocates to the cell nucleus to regulate neuronal differentiation. BREAST CANCER: SCIENTISTS INDENTIFY SIGNALING PATHWAY DRIVING DEADLY SUB-TYPE An intra cellular pathway not previously linked to breast cancer is driving a sub-type of the disease that is highly lethal and disproportionately over-represented in African-American women, researchers at the University of California, Los Angeles report. The pathway regulates how cells identify and destroy proteins and represents a class of genes called proteasome targeting complexes. The work shows that basal cancer cells degrade the tumor suppressor gene p27 by making a new type of proteasome targeting complex. The gene p27 is one of a handful of proteins that are expressed in normal cells and act to prevent rapid cell growth, which is indicative of cancer. Beyond chemotherapy, no specific therapeutic target has been identified for this sub-type of cancer, found in between 12 to 15 percent of breast cancers in the general population and up to 25 percent of cases in African American women. The research, performed in animal models and human breast cancer cell lines, was published in the journal Genes and Development.
ANTIANGIOGENICS: CANCER DRUGS MAY BUILD, NOT TEAR DOWN, BLOOD VESSELS Researchers at the Moores Cancer Center at the University of California, San Diego in La Jolla, California have found evidence that blocking vascular endothelial growth factor or VEGF doesn’t really halt the process new blood vessel formation in tumors. Instead, they said, it actually props up existing blood vessels, making them stronger and more normal, and in some cases the tumors larger. But as a result, the tumor is more vulnerable to the effects of chemotherapy drugs. Scientists have thought that one way to foil a tumor from generating blood vessels to feed its growth—a process called angiogenesis—was by creating drugs aimed at stopping a key vessel growth-promoting protein. But now the opposite seems to be true. In a paper in the journal Nature, the researchers report that their findings provide an explanation for recent evidence showing that anti-angiogenesis drugs such as Avastin can be much more effective when combined with chemotherapy. The results may lead to better treatment strategies for a variety of cancers. HIV: GERON SAYS TELOMERASE ACTIVATOR ENHANCES ANTIVIAL FUNCTION OF IMMUNE CELLS FROM INFECTED DONORS
Menlo Park, California-based Geron said the publication of preclinical data on TAT2, a small molecule telomerase activator, show that human CD8+ T-cells from HIV-infected donors exposed to TAT2 exhibited increased telomerase activity. This resulted in retardation of telomere shortening, an increase in T-cell proliferation, and enhancement of critical antiviral functions against HIV-1. The studies, published in the online edition of The Journal of Immunology, were conducted by researchers at the University of California, Los Angeles in collaboration with Geron scientists. Current treatments of HIV/AIDS are primarily directed at the HIV virus itself, but Geron said the understanding of telomerase has led to a pharmacologic approach aimed at enhancing the anti-HIV function of a patient’s T-cells by activating telomerase. This is consistent with clinical studies showing that HIV-positive individuals with significantly higher lymphocyte telomerase activity are able to control their infection for a longer period of time compared to other patients, with lower lymphocyte telomerase activity, who progress quickly to AIDS, the company said. CD8+ T-cells play a crucial role in controlling HIV-1 infection by killing infected cells and secreting antiviral cytokines in response to viral stimulation. Most non-dividing cells show little or no telomerase activity, but telomerase is up-regulated by cells that must repeatedly divide, such as T-cells responding to viral antigen. However, during chronic HIV-1 infection, CD8+ T-cells exhaust their ability to up-regulate telomerase, leading to critically short telomeres and other changes associated with replicative senescence (cellular aging), reducing their antiviral activity. HEART ATTACK: LOW-DOSE ASPIRIN DOES NOT APPEAR TO REDUCE RISK OF HEART ATTACK IN DIABETIC PATIENTS
Low-dose aspirin as primary prevention did not appear to significantly reduce the risk of of coronary, cerebrovascular, and peripheral vascular events in patients with type 2 diabetes, according to a study in JAMA. However, aspirin did significantly reduce the combination of fatal coronary and fatal cerebrovascular events. Myocardial infarction (heart attack) and ischemic stroke are leading causes of mortality and morbidity in patients with type 2 diabetes. Given the rapid increase in the number of patients with type 2 diabetes worldwide and especially in Asia, establishing effective means of primary prevention of coronary and cerebrovascular events is an important public health priority. The researchers said while the study, published in JAMA, did not find that low-dose aspirin significantly reduced the risk of atherosclerotic events in primary prevention therapy in patients with type 2 diabetes. They said more research is needed. HEART DISEASE: ANTHERA DRUG SHOWS ANTI-INFALMMATORY EFFECT AND LDL REDUCTION IN PATIENTS WITH CHD
Hayward, California-based Anthera Pharmaceuticals presented positive data on its lead product, varespladib at the American Heart Association Annual Conference in New Orleans, Louisiana. Anthera has completed two mid-stage clinical trials in varespladib for the treatment of coronary heart disease. The company said results from the most recent study showed that in patients with coronary heart disease currently on statin therapy—varespladib had a significant anti-inflammatory effect as measured by a greater than 20 percent relative reduction in C-reactive protein. The drug also had a substantial reduction in the target enzyme and pro- inflammatory marker, secretory phospholipase A2. In patients with coronary heart disease, Varespladib resulted in a significant 15 percent reduction in LDL and caused a significant reduction in small LDL particles in CHD patients HEART FAILURE: CYTOKINETICS SAYS INTERIM ANALYSIS OF DRUG TRIAL SHOWS IMPROVEMENTS
South San Francisco, California-based Cytokinetics presented encouraging interim analyses of data from a mid-stage clinical trial of its experimental drug CK-1827452 in stable heart failure patients during a Special Program at the 2008 Scientific Sessions of the American Heart Association. CK-1827452 is a novel cardiac myosin activator being developed for the potential treatment of patients with either acutely decompensated or chronic heart failure. CK-1827452 is the subject of a collaboration and option Agreement between Cytokinetics and Amgen. These interim analyses demonstrated statistically significant increases in systolic ejection time, and fractional shortening at CK-1827452 plasma concentrations greater than 100 ng/mL, and statistically significant increases in stroke volume at CK-1827452 plasma concentrations greater than 200 ng/mL. In addition, there were statistically significant correlations between increasing CK-1827452 plasma concentration and increases in systolic ejection time, stroke volume, fractional shortening, and cardiac output. There were also statistically significant correlations between increasing CK-1827452 concentration and decreases in supine and standing heart rate and left ventricular end-systolic volume. ETHANOL INTOLERANCE: RAPTOR REPORTS POSITIVE RESULTS IN MID-STAGE TRIAL OF CONVIVIA
Novato, California-based Raptor Pharmaceuticals reported positive results in a mid-stage clinical trial of oral 4-methylpyrazole (4-MP), the active ingredient in its drug Convivia, in subjects with a deficiency of the liver enzyme aldehyde dehydrogenase (ALDH2), or ethanol intolerance. ALDH2 deficiency, sometimes referred to as “Asian flushing syndrome,” is an inherited metabolic disorder affecting 40 percent to 50 percent of East Asian populations, impairing the activity of ALDH2. When people with ALDH2 deficiency drink alcoholic beverages, there is an accumulation of acetaldehyde, a carcinogenic intermediate in the metabolism of ethanol, in blood and tissues. The company said the study results demonstrated that the active ingredient in Convivia significantly reduced heart palpitations (tachycardia), which are commonly experienced by ALDH2 deficient people who drink, at all dose levels tested. The study also found that the 4-MP significantly reduced peak acetaldehyde levels and total acetaldehyde exposure in a subset of the study participants who possess specific genetic variants of the liver ADH and ALDH2 enzymes. This subset represents approximately one-third of the ALDH2 deficient adult population. SHORT STATURE: TERCICA REPORTS POSITIVE RESULTS FROM LATE-STAGE CLINICAL TRIAL
Brisbane, California-based Tercica, a wholly-owned subsidiary of Ipsen, said a phase IIIb clinical trial demonstrated that Increlex achieved statistically significant dose-dependent first-year height velocity increases in children with Primary IGF-1 Deficiency when administered as a twice-daily injection. A second exploratory study demonstrated that when Increlex is given as a once-daily regimen in the Primary IGF-1 Deficiency population, Increlex achieved statistically significant dose-dependent first-year height velocity increases. Tercica presented the data from both studies along with other data presentations for Increlex at the 13th International Congress of Endocrinology meeting in Rio de Janeiro, Brazil. Increlex is marketed in the United States and other countries for the treatment of growth failure in children with Severe Primary IGFD using twice-daily injections. San Diego-based Cardium Therapeutics and its operating unit InnerCool Therapies, said they have developed a pelvic cooling catheter system called UroCool, which is designed to induce localized cooling during surgery for prostate cancer (radical prostatectomy). The technology is being applied in collaboration with urologists at the University of California, Irvine and is the subject of an exclusive licensing agreement with the University of California. A regulatory application for FDA 510(k) clearance of InnerCool’s UroCool catheter is expected to be submitted in the first quarter of 2009. The UC Irvine urologists are conducting clinical studies designed to demonstrate safety and confirm the potential benefits of localized cooling during robotic-assisted prostatectomy, which is now the most common surgical technique for prostate cancer. The UroCool catheter is designed to be placed within the rectal cavity adjacent to the prostate during surgery. UroCool is used in conjunction with InnerCool’s Celsius Control Console which circulates cold saline in a closed loop within the catheter to allow for localized cooling. The urologists believe the localized cooling technique can reduce tissue damage and inflammation and thereby provide a faster return of bladder control and possibly erectile function.
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