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Archive - Feb 25, 2010

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Second DISC-1 Study Suggests Reason for Adolescent Onset of Schizophrenia

In a second study, researchers at Johns Hopkins and collaborating institutions have identified a mechanism whereby alterations in the DISC-1 (disrupted in schizophrenia-1) gene may underlie the adolescent onset of schizophrenia. In this second study, published in the March issue of Nature Neuroscience, the research team examined DISC-1's role in forming connections between nerve cells. The first study looked at the long-term effects of transient DISC-1 gene expression changes near the time of birth in a mouse model. This first study was published in the February 25, 2010 issue of Neuron and has previously been reported on in BioQuick News. Taken together, the results of both studies suggest that anatomical differences that seem to be influenced by the DISC-1 gene cause problems that start before birth, but surface only in young adulthood. "If we can learn more about the cascade of events that lead to these anatomical differences, we may eventually be able to alter the course of schizophrenia. During adolescence, we may be able to intervene to prevent or lessen symptoms," said second study senior author and first study co-author Dr. Akira Sawa, professor of psychiatry and director of the program in molecular psychiatry at the Johns Hopkins University School of Medicine. Numerous studies have previously suggested that schizophrenia results from abnormal connectivity. The fact that symptoms typically arise soon after adolescence, a time of massive reorganization of connections between nerve cells, supports this idea. The scientists began their second study by surveying rat nerve cells to see where DISC1 was most active. Unsurprisingly, they found the highest DISC-1 activity in connections between nerve cells.

Female Sex Hormone Found in Plant

In a finding that overturns conventional wisdom, scientists have reported the first discovery of the female sex hormone progesterone in a plant. Until now, scientists thought that only animals could make progesterone. A steroid hormone secreted by the ovaries, progesterone prepares the uterus for pregnancy and maintains pregnancy. A synthetic version, progestin, is used in birth control pills and other medications. "The significance of the unequivocal identification of progesterone cannot be overstated," the article, by Dr. Guido F. Pauli and colleagues, claimed. "While the biological role of progesterone has been extensively studied in mammals, the reason for its presence in plants is less apparent." The authors speculate that the hormone, like other steroid hormones, might be an ancient bioregulator that evolved billions of years ago, before the appearance of modern plants and animals. The new discovery may change scientific understanding of the evolution and function of progesterone in living things. Scientists had previously identified progesterone-like substances in plants and speculated that the hormone itself could exist in plants. But researchers had not found the actual hormone in plants until now. Dr. Pauli and colleagues used two powerful laboratory techniques, nuclear magnetic resonance and mass spectroscopy, to detect progesterone in leaves of the Common Walnut (or English Walnut) tree (Juglans regia). They also identified five new progesterone-related steroids in a plant belonging to the buttercup family. The discoveries were reported online on January 28, 2010 in the American Chemical Society's Journal of Natural Products. [Press release] [Journal of Natural Products abstract]

New Strategy Rapidly Identifies Two Prototype Drugs

A new and comprehensive drug development strategy that starts with extensive screening of potential targeting peptides to rapidly identify prototype small-molecule drugs has produced two that target the EGFR and VEGFR pathways in novel ways, according to a research team led by scientists at The University of Texas M.D. Anderson Cancer Center "The conceptual advance here is to demonstrate how to go rapidly from screening to structural-functional analysis to drug prototype in a few years," said co-senior author Dr. Wadih Arap, of the David H. Koch Center at M.D. Anderson. "The practical outcome is a pair of new drug candidates, one that acts as a decoy to inhibit a cancer-promoting pathway and another that blocks angiogenesis (the development of new blood vessels), which has the potential to treat both cancer and retinopathies that cause blindness," said co-senior author Dr. Renata Pasqualini, also of the David H. Koch Center. The group's approach begins by screening the target receptors with a phage display library used by Drs. Arap and Pasqualini. This method screens billions of viral particles that each display a different peptide on its outer coat to find those that fit into the receptor as a key goes into a lock. Candidate peptides are next winnowed by using structural and functional analysis. Once a peptide is identified and tested, the researchers take an additional step to synthesize a new version of the peptide more suited for use as a drug.

Stem Cells Restore Sight in Retina-Damaged Mice

Researchers have successfully used mouse embryonic stem cells to replace diseased retinal cells and restore sight in a mouse model of retinitis pigmentosa. This strategy could potentially become a new treatment for retinitis pigmentosa, a leading cause of blindness that affects approximately one in 3,000 to 4,000 people, or a total of 1.5 million people worldwide. The approach also holds promise for the treatment of other retina-damaging diseases. "This research is promising because we successfully turned stem cells into retinal cells, and these retinal cells restored vision in a mouse model of retinitis pigmentosa," said Dr. Stephen Tsang, assistant professor of ophthalmology, pathology, and cell biology at Columbia University Medical Center, and lead author of the paper. "The transplanted cells not only looked like retinal cells, but they functioned like them too." In Dr. Tsang's study, sight was restored in one-fourth of the mice that received the stem cells. However, complications of benign tumors and retinal detachments were seen in some of the mice, so Dr. Tsang and colleagues will optimize techniques to decrease the incidence of these complications in human embryonic stem cells before testing in human patients can begin. "Once the complication issues are addressed, we believe this technique could become a new therapeutic approach for not only retinitis pigmentosa, but age-related macular degeneration, Stargardt disease, and other forms of retinal disease that also feature loss of retinal cells," said Dr. Tsang. Specialized retinal cells called the retinal pigment epithelium help maintain vision.

Single-Dose HIV DNA Vaccine Produces Specific Immunity in Primates

For the first time, researchers have shown that a single-dose HIV DNA vaccine can induce a long-lasting HIV-specific immune response in nonhuman primates, a discovery that could prove significant in the development of HIV vaccines. "Our comprehensive analysis demonstrated for the first time the capacity of a single high dose of HIV DNA vaccine alone to induce long-lasting and polyfunctional T-cell responses in the nonhuman primate model, bringing new insights for the design of future HIV vaccines," said the researchers from Emory University in the United States and the Institut National de la Recherche Agronomique in France. HIV is persistently spreading at epidemic rates throughout the world, emphasizing the need for a vaccine that can substantially reduce viral loads and minimize transmission. In a previous study, the research team had successfully induced long-lasting and potent HIV-specific immune responses in mice following immunization with a single-dose SHIV DNA-based vaccine. SHIV is a virus that combines genes from HIV in a genetic background of simian immunodeficiency virus (SIV). In the current study, rhesus macaques were immunized with a single high dose of the SHIV DNA-based vaccine and monitored for vaccine-induced immune responses. Results showed that all immunized monkeys developed broad HIV-specific T-cell immune responses that persisted for months. The researchers detailed their findings in the February 2010 issue of the Journal of Virology. [Press release] [J. Virology abstract]