A scientist from The Scripps Research Institute's Florida campus has been awarded a pair of research grants from the National Institutes of Health (NIH) totaling just over $1.4 million to pursue drug discovery work in both Alzheimer's disease and alcoholism. The grants have gone to Claes Wahlestedt, who is professor and director of Neuroscience Discovery at Scripps Florida.

The first grant, which will fund the study of non-coding RNA modulators in Alzheimer's disease, is for approximately $924,000 over two years; the other award, about $484,000 for one year, will be used to study and develop novel ligands for a specific receptor that plays a role in alcohol dependence.

The studies are being funded through the American Recovery and Reinvestment Act, the economic stimulus package passed by the Congress in February. To date about 100 Scripps Research Institute investigators in California and Florida have won supplemental grants from the NIH under the Recovery and Reinvestment Act.

An Under-Studied Disease

Wahlestedt is excited about the research that his new grants will make possible.

"[The new grants] will help move our research forward in two very important areas," said Wahlestedt. "The key to our ongoing research is that we shouldn't duplicate what's already being done but should seek out under-studied areas like drug discovery for alcohol abuse where any progress could truly have an impact on patient lives."

Alcohol dependence is not considered a major target by companies in the biotech-pharmaceutical industry, Wahlestedt said. "In our study, we are searching for novel ligands for the nociceptin receptor," he said.

The nociceptin receptor may be involved in some brain disorders and could be a novel target in the development of new drugs to treat alcohol abuse; drug candidates bind to proteins like the nociceptin receptor and alter their function.

In the new study, Wahlestedt will work closely with Tom Bannister, associate scientific director of the Scripps Florida Translational Research Institute who will help design and synthesize novel receptor ligands through cheminformatics and various compound libraries; cheminformatics uses computers to store and retrieve vast amounts of information about chemical compounds used in molecular design.

An Area of Interest

The two-year Alzheimer's disease study is an expansion of Wahlestedt's longtime interest in the disease. In research published in 2008, Wahlestedt and his colleagues showed that a noncoding form of RNA controlled the expression of ß-secretase-1 (BACE1), an enzyme critical to Alzheimer's disease progression. Their work offered a rare positive glimpse of therapeutic potential in what has been a difficult research area. There are several different types of small non-coding RNA, including microRNA and small interfering RNA (siRNA). The Wahlestedt laboratory also has a strong interest in long non-coding RNA, which regulate gene expression.

"Once again we're trying to gain a deeper understanding of the disease by creating a comprehensive inventory of non-coding RNA associated with Alzheimer's disease," Wahlestedt said. "We hope to develop biomarkers that can be used to determine the efficacy of potential treatments during clinical trials. While this is still very experimental, we think it could develop into something with a very practical use."

Currently, the most established source of biomarkers is cerebrospinal fluid (CSF), which can be obtained by lumbar puncture - sometimes known as a spinal tap.

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