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Archive - Apr 2011 - Story

April 29th

Gene Therapy Approach Shows Promise for Macular Degeneration

A gene therapy approach using a protein called CD59, or protectin, shows promise in slowing the signs of age-related macular degeneration (AMD), according to a new in vivo study by researchers at Tufts University School of Medicine. Led by senior author Dr. Rajendra Kumar-Singh, the researchers demonstrated for the first time that CD59 delivered by a gene therapy approach significantly reduced the uncontrolled blood vessel growth and cell death typical of AMD, the most common cause of blindness in the elderly. The study was published on April 28 in PLoS ONE. Activation of the complement system, a part of the immune system, is responsible for slowly killing cells in the back of the eye, leading to AMD. Activation of this system leads to the generation of pores or holes known as 'membrane attack complex' or MAC in cell membranes. CD59 is known to block the formation of MAC. "CD59 is unstable and hence previous studies using CD59 have had limited success. The gene therapy approach that we developed continuously produces CD59 in the eye and overcomes these barriers, giving us renewed hope that it can be used to fight the progression of AMD and potentially other diseases," said Dr. Kumar-Singh. Dr. Kumar-Singh is associate professor in the department of ophthalmology at Tufts University School of Medicine (TUSM) and member of the genetics; neuroscience; and cell, molecular, and developmental biology program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts. Dr. Kumar-Singh and colleagues delivered CD59 to the eye using a deactivated virus similar to one previously shown to be safe in humans. Using an established mouse model of age-related macular degeneration, they found that eyes treated with CD59 had 62 percent less uncontrolled blood vessel growth and 52 percent less MAC than controls.

April 28th

New Technique Reveals Functional Gene Networks in C. elegans

An international team of scientists, led by researchers at the University of California, San Diego School of Medicine, has developed a new method for discerning the functions of previously uncharacterized genes and placing them in interactive, functional networks that reveal how gene products interact to bring about cellular events. The research is published in the April 29, 2011 issue of Cell. The effort was led by principal investigators Dr. Karen Oegema, professor of cellular and molecular medicine and head of the Laboratory of Mitotic Mechanisms in the Ludwig Institute for Cancer Research at UC San Diego, and Dr. Kristin C. Gunsalus, assistant professor in the Center for Genomics and Systems Biology in the Department of Biology at New York University. More than a decade of genome sequencing projects has generated a comprehensive "parts" list of the genes required to build an organism, an inventory of the necessary cellular building blocks. But the functions of many of these genes remain unknown, preventing researchers from fully deciphering their cellular pathways and how their interactions might shed light on human disease. One of the stars of this research is Caenorhabditis elegans, a tiny, much-studied worm that is an important model system for understanding processes in animal cells. In recent years, scientists have sought to create systemic catalogs of its gene functions, and those of other model organisms. These large-scale efforts place genes in interactive networks. Within these networks, proximity reflects similarity of function. In other words, genes with similar functions are directly linked and genes with dissimilar functions are further apart. The functions of uncharacterized genes are inferred based upon their proximity to genes whose functions are known.

Prairie Voles Used in Study of Autism Drug Treatment

Researchers at the Center for Translational Social Neuroscience (CTSN) at Emory University are focusing on prairie voles as a new model to screen the effectiveness of drugs to treat autism. They are starting with D-cycloserine, a drug Emory researchers have shown enhances behavioral therapy for phobias and also promotes pair bonding among prairie voles. Giving female voles D-cycloserine, which is thought to facilitate learning and memory, can encourage them to bond with a new male more quickly than usual. The results were published online on April 8, 2011, and will appear in a future issue of Biological Psychiatry. "The prairie vole model has enabled us to learn about complex neural pathways in social areas of the brain," says senior author Dr. Larry Young. “We believe these insights will be useful in identifying drugs that enhance social cognition and learning. Drugs with these properties, particularly when combined with behavioral therapies, may be beneficial in the treatment of autism spectrum disorders." Dr. Young is division chief of Behavioral Neuroscience and Psychiatric Disorders at the Yerkes National Primate Research Center, William P. Timmie professor of psychiatry and behavioral sciences at Emory University School of Medicine and director of the Emory CTSN. He and his colleagues have been studying the prairie vole for more than 15 years as a model to explore the neurobiology of prosocial behaviors, including cooperation, compassion, bonding, and social reciprocity. Now, they are hoping to identify drugs that can enhance social learning in individuals with autism spectrum disorders, and they think the process of pair bonding in the prairie vole may be a useful tool for identifying new therapies.

April 26th

Most Obese Adolescents Are Lacking Vitamin D

A new study from Hasbro Children's Hospital in Providence, Rhode Island, has found that most obese adolescents are lacking in vitamin D. The researchers call for increased surveillance of vitamin D levels in this population and for further studies to determine if normalizing vitamin D levels will help to lower the health risks associated with obesity. The study is published in the May edition of the Journal of Adolescent Health. Obesity in children and adolescents has reached epidemic proportions, with a prevalence of 16.4 percent among 10 to 17 year olds as of 2007. The increased prevalence of obesity may lead to increased risk of diabetes, hypertension, and cardiovascular disease, as well as to an increased risk of cancer. Some of these health consequences of obesity have also been associated with vitamin D deficiency or insufficiency. In addition, vitamin D status is significantly associated with muscle power/force, and therefore, a deficiency may interfere with the obese adolescent's ability to increase physical activity. Lead author Dr. Zeev Harel, a pediatrician specializing in adolescent medicine at Hasbro Children's Hospital, reports that screening obese adolescents for vitamin D status by measuring their blood 25 OH D level has become a routine protocol at the Adolescent Health Center of Hasbro Children's Hospital since 2007. For this retrospective study, Harel and his co-authors explored the prevalence of low vitamin D status among 68 obese adolescents, and examined the impact of treatment of low vitamin D status in these patients. The study found that low vitamin D status was present in all of the girls (72 percent deficient and 28 percent insufficient) and in 91 percent of the boys (69 percent deficient and 22 percent insufficient).

April 26th

Targeted Topical Treatment May Prevent Melanoma

While the incidence of melanoma continues to increase despite the use of sunscreen and skin screenings, a topical compound called ISC-4 may prevent melanoma lesion formation, according to Penn State College of Medicine researchers. "The steady increase in melanoma incidence suggests that additional preventive approaches are needed to complement these existing strategies," said Dr. Gavin Robertson, professor of pharmacology, pathology, dermatology, and surgery, and director of the Penn State Hershey Melanoma Center. Researchers targeted the protein Akt3, which plays a central role in 70 percent of melanoma by preventing cell death and has the potential to prevent early stages of melanoma. "The Akt3 signaling pathway is deregulated in the majority of melanomas, making it a promising target which, if inhibited, could correct the apoptotic -- or cell death -- defect in melanocytic lesions, thereby preventing this disease," Dr. Robertson said. Isothiocyantes were identified as inhibitors of Akt3. These are naturally occurring compounds found in cruciferous vegetables like broccoli and brussels sprouts that have anticancer properties. Unfortunately, previous research showed these compounds have low chemotherapy potency on melanoma cells because high concentrations are needed to be effective. To create a more potent version, Penn State Hershey Melanoma Center researchers previously developed isoselenocyanates (e.g., ISC-4), by replacing sulfur with selenium. Researchers have now found that repeated topical application of ISC-4 can reduce tumor cell expansion in laboratory-generated human skin by 80 to 90 percent and decrease tumor development in mice skin by about 80 percent. The research also showed that the use of the compound is safe.

Brain Protein May Be Useful Target in Colorectal Cancer

Tumor progression is usually ensured by more than one proliferative mechanism. When one of these is shut down by a specifically targeted drug, other mechanisms may emerge. While these events may lead to treatment failure, they may also become an opportunity for researchers to identify novel targets to be further explored. In a paper recently published online in the journal Oncology (Vol. 79, pages 430-439, 2011), Dr. Rafael Roesler and colleagues describe a novel potential drug target in colorectal cancer. Colorectal cancer (CRC) is the fourth most common cancer in men and the third in women worldwide. It is a frequent cancer, with more than 1 million new cases every year and a poor survival rate. Rapid increases in CRC incidence have been observed mainly in emerging economies. These increases are attributed to changes in diet, life style, and patterns of physical activity. In Western countries, only 55% of the patients are alive 5 years after diagnosis, with most patients dying from metastatic disease. Although a number of treatment options are available for CRC patients, including surgery, chemotherapy, and biologic therapies targeting two different mechanisms—angiogenesis (drug: bevacizumab) and epidermal growth factor receptors (drugs: cetuximab and panitumumab)—new treatment options are required to improve survival rates. The search for novel targets led Dr. Roesler at the Federal University of Rio Grande do Sul (UFRGS) Brazil, Dr. Gilberto Schwartsmann, and graduate student Caroline Brunetto de Farias, among others, to investigate whether a brain-derived protein known to be involved in tumor growth, metastasis, and drug resistance in a number of cancers, including some non-neurological cancers, could also be found in CRC. The team led by Dr.

RAD Technology May Simplify Genome Sequencing

Take millions of puzzle pieces containing partial words and put them back together into full words, sentences, paragraphs and chapters until the book these random parts came from is rebuilt. That daunting process in not unlike sequencing an organism's genome, says University of Oregon biologist Dr. Eric A. Johnson, a member of the UO Institute of Molecular Biology. His lab developed a patent-pending technology for discovering differences between genomes called restriction-site associated DNA markers, or RAD. They have now shown that RAD can also be used to help put a genome sequence together. The original RAD technique, unveiled in 2005, led to the UO spinoff company Floragenex, which uses the technology in plant genetics. More recently, Dr. Johnson and UO colleague Dr. William A. Cresko used it to identify genetic differences in threespine stickleback, a fish, which evolved separately after environmental conditions had isolated some of the saltwater fish into freshwater habitats. Now, after three years of research, adapting the technology along the way as sequencing tools advanced, Dr. Johnson, Dr. Cresko, and three UO colleagues provide a proof-of-principle paper published online on April 13, 2011, in PLoS One. The NIH-funded research documents that the new method, called RAD paired-end contigs, works and provides accurate sequencing results. "The RAD sequence is a placeholder that identifies one small region of a genome," Dr. Johnson said. "We showed that this technique lets us gather together appropriate nearby sequences and piece them together." In just seconds, a section is completed, he said. In a matter of hours, he added, an entire genome's sequence emerges. Using the book analogy, Dr.

April 24th

Blocking Cytokine May Be Key to Treatment of Multiple Sclerosis

Reporting online on April 24, 2011, in Nature Immunology, Jefferson Medical College neuroscientists have identified a driving force behind autoimmune diseases such as multiple sclerosis (MS), and suggest that blocking this cell-signaling molecule is the first step in developing new treatments to eradicate these diseases. Researchers led by Dr. Abdolmohamad Rostami, Professor and Chairman of the Department of Neurology at Jefferson Medical College of Thomas Jefferson University, found that GM-CSF, which stands for granulocyte-macrophage colony-stimulating factor, appears to be the key culprit in the onset of MS, because without it, T helper 17 (Th17) cells did not induce the MS-like disease in an experimental animal model. Th17 cells have been shown to play an important pathogenic role in humans and experimental models of autoimmune diseases, but the mechanisms behind this have remained elusive until now. "There was no connection between GM-CSF and Th17 cells before," said Dr. Rostami. "What we have shown in this paper is that GM-CSF derived from Th17 cells is important in the cell-signaling process that leads to inflammation in the central nervous system. Now we know how the Th17 cells work and a better understanding of this mechanism and biology leads to new therapeutics," he added. The results suggest that blocking GM-CSF activity may be a successful therapeutic strategy in MS, one of the most common neurological diseases affecting young adults, and other autoimmune diseases, said Dr. Rostami, who is also the Chair of Neurology at Thomas Jefferson University Hospital. These findings identify the interleukin-23 (IL-23)/ Th17/GM-CSF axis as the major pathway in pathogenesis of autoimmune central nervous system inflammation and likely other autoimmune diseases.

April 21st

New Hope for Treatment of Shingles

Researchers at the University of Georgia and Yale University have discovered a compound with the potential to be more effective than existing agents in treating the very painful blisters known as shingles—a condition that affects up to 30 percent of Americans, mostly elderly, and for which no specific treatment exists. Most adults remember the fever, itchy blisters, and possibly tiny scars they experienced as children when they had chickenpox, which is caused by the varicella-zoster virus, or VZV. Unfortunately, that memory can come back—with a vengeance—when they are older. The VZV virus from childhood chickenpox hides in the nerves, emerging most frequently in adults over the age of 60 as a blistering rash on one side of the body. The rate of complications, including nerve pain that can persist for months or years after the shingles attack is gone, also increases with age. The novel and effective anti-shingles agent called L-BHDA may change that. Rights to the shingles treatment have been licensed to Bukwang Pharmaceutical Company for preclinical investigations by the University of Georgia Research Foundation, Inc. and Yale University. "We need new options for medications with increased potency and specificity that can treat VZV, including strains that may be resistant to existing drugs," said medicinal chemist Dr. Chung (David) Chu, Distinguished Research Professor of Pharmaceutical and Biomedical Sciences at UGA, one of the inventors of L-BHDA. A collaboration between Dr. Chu and co-inventor Dr. Yung-Chi (Tommy) Cheng, the Henry Bronson Professor of Pharmacology at Yale, has resulted in an extensive portfolio of antiviral compounds that target such diseases as HIV, shingles, hepatitis, and cancers. Dr.

Mechanism of B Cell Differentiation Clarified

An article in the April 19, 2011 issue of Science Signaling by researchers at the RIKEN Research Center for Allergy and Immunology (RCAI) in Japan, and colleagues, has clarified for the first time the mechanism governing differentiation of B cells into antibody-producing plasma cells. The finding establishes a role for the extracellular signal-regulated kinase (ERK) signaling pathway in B cell differentiation, a key step toward the development of B cell-targeted drugs for treatment of autoimmune diseases and allergies. As the only cells in the body that produce antibodies, B cells play an essential role in the immune system's defense against bacteria and viruses. Differentiation of B cells into antibody-producing plasma cells is central to this role, initiating the production of antibodies whose targeted binding mechanism enables the immune system to identify and neutralize foreign objects. The mechanism underlying this differentiation process, however, remains unknown. To better understand this mechanism, the research group focused on the signaling of the extracellular signal-regulated kinases (ERK), intracellular signaling molecules known to play an important role in the cell cycle and survival of immune cells. Hoping to glean insights into the role of ERKs in B cell differentiation into plasma cells, the researchers generated mice deficient in two different ERKs, ERK1 and ERK2, and studied the effect of this deficiency on the fate of B cells. What they found confirmed that ERKs are in fact essential to B cell differentiation: B cells in mice without these key molecules were unable to form plasma cells.