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Archive - Apr 30, 2012

Scripps Scientist Receives $1.5 Million to Use RNA Approach to Design Drugs

A scientist from the Florida campus of The Scripps Research Institute has been awarded $1.5 million from the National Institutes of Health to develop new computer-driven design methods to find new therapeutics targeting RNA. Matthew Disney, Ph.D., an associate professor at Scripps Research, is the principal investigator for the four-year study. RNA was once considered a passive messenger, used only to carry copies of the DNA needed to produce or translate proteins. All that changed when it was found that RNA could produce chemical reactions that, for example, cause proteins to fold into various forms. RNA is an increasingly important potential target for the design of small molecule therapeutics, although methods to design small molecule drugs that bind to RNA and affect its function are still in their infancy. "The rational design of small molecules that exploit therapeutic targets from genomic sequence was one of the promises of the human genome project, but people had no idea of how to do it," Dr. Disney said. "As a result, most targets—especially RNA targets—represent untapped potential." A computer program created by Dr. Disney merges information on the interaction between small molecules (potential drugs) and RNA folds that contribute to specific diseases. Disney said his approach differs from conventional "top-down" methods that normally screen an RNA target against a broad chemical library. "Our bottom-up approach uses information about the small RNA motifs such as internal loops or hairpins that a small molecule ligand prefers to bind," he said. Using this method, Dr. Disney recently successfully designed several small molecules that are strongly active against myotonic dystrophy type 1, the most common form of muscular dystrophy.

Novel Mutations Linked to Autism Identified in Genes Associated with Fragile X

A new study, published in the April 26, 2012 issue of Neuron, reports the discovery of several genes associated with autism and finds evidence for a shared genetic mechanism underlying autism and fragile X syndrome, the most common genetic cause of intellectual disability. It is well established that genetic variation caused by mutation can lead to autism spectrum disorders, and research has repeatedly implicated "de novo" mutations, those that show up for the first time in affected children, as being particularly relevant. Identification of the specific genes associated with autism may lead to much needed advances in the diagnosis and treatment of autism spectrum disorders. The current study, led by Dr. Michael Wigler from Cold Spring Harbor Laboratory, used gene sequencing methods to look at nearly 350 families with healthy children and children on the autistic spectrum, part of the larger Simons Simplex Collection. Specifically, the researchers looked for mutations that were present in the children, but not in their parents. The team found that autism is linked with the types of new mutations that are likely to disrupt the function of a gene. By disrupting one of the pair of healthy genes that we normally inherit, such mutations alter "gene dosage." There was a two-fold higher incidence of such mutations in the affected child than in the healthy child, but little to no difference in the overall incidence of much more prevalent types of mutations. The results also showed that children with older parents have more new mutations. This is consistent with other recent reports and perhaps explains why older parents are more likely to have children on the autism spectrum.

Pig Mucins Are Effective As Anti-Viral Agents for Consumer Products

Scientists are reporting that the mucus lining the stomachs of pigs could be a long-sought, abundant source of "mucins" being considered for use as broad-spectrum anti-viral agents to supplement baby formula and for use in personal hygiene and other consumer products to protect against a range of viral infections. Their study appeared online on April 4, 2012 in the American Chemical Society journal Biomacromolecules. In the report, Dr. Katharina Ribbeck, Eugene Bell Career Development Professor of Tissue Engineering in MIT’s Department of Biological Engineering, and colleagues point out that mucus, which coats the inside of the nose, mouth, and vagina, is the immune system's first line of defense. The slimy secretion traps disease-causing microbes, ranging from influenza virus to HIV (which causes AIDS) before they can cause infection. That has led to consideration of mucin, the main component of mucus, for use as an anti-viral agent in a variety of products. However, existing sources of mucins, such as breast milk, cannot provide industrial-sized quantities. Large amounts of mucus exist in the lining of pigs' stomachs, and the authors set out to determine if pig mucus — already used as a component of artificial saliva to treat patients with "dry mouth," or xerostomia — has the same anti-viral activity. They found that pig mucus is effective at blocking a range of viruses, from strains of influenza to the human papilloma virus, which is associated with cervical and oral cancer. They report that pig mucins could be added to toothpastes, mouthwashes, wound ointments, and genital lubricants to protect against viral infections. "We envision porcine gastric mucins to be promising antiviral components for future biomedical applications," the report says.