The Scripps Research Institute and the University of Pennsylvania School of Medicine have been awarded approximately $8.2 million over five years to develop novel compounds that could eventually become drug candidates for the treatment of tobacco addiction. Of the funds awarded, $5.7 million will go to Scripps Research, and $2.5 million to the University of Pennsylvania.
The grant from the National Institutes of Health's (NIH) National Institute on Drug Abuse (NIDA) will fund research focused on potential new treatments for tobacco addiction, specifically the development of novel kinds of potent and selective compounds that affect nicotinic receptors in the brain.
Consortium principal investigators are Paul J. Kenny, Ph.D., an associate professor in the Department of Molecular Therapeutics on the Jupiter, Florida campus of Scripps Research, and Jon Martin Lindstrom, PhD, professor of Neuroscience at the University of Pennsylvania School of Medicine.
"This project capitalizes on the unique drug discovery capabilities at Scripps Florida, and combines that with the work Jon Lindstrom has been doing on defining the structure and function of nicotinic receptors," Kenny said. "We have exceptional collaborators here at Scripps Florida, including Ted Kamenecka and Michael Cameron. In combination with Jon's expertise, we believe that the collaboration funded by this generous grant has the potential to produce effective therapeutic compounds to help people stop smoking." Lindstrom added, "We have been studying the properties of cloned human nicotinic receptor subtypes in vitro for years with the hope of using the methods and cell lines we have developed to discover new drugs for these receptors. This collaboration with Paul, and the support of NIDA, provides critical elements to turn these hopes into reality."
Recent studies have shown that genetic variations in several nicotinic receptor subunits (building blocks of the "receptor" proteins that respond to nicotine) actually increase vulnerability to tobacco addiction, Kenny said, although initially little was actually known about these variations or their function.
"We got interested in one of these lesser-studied subunits that influences smoking and have developed a good understanding of how it works in the brain," he said. "It seems that this subunit is part of a distinct subtype of nicotinic receptor that actually protects against tobacco addiction. Now we want to find compounds that boost the activity of this receptor subtype in the hopes that they will be effective in reducing tobacco smoking. This approach contrasts with most anti-smoking treatments today, which are aimed at reducing the positive impact of nicotine on the brain's reward centers. Instead, we aim to enhance the inhibitory effects of the drug on these reward centers."
Kenny said he met Lindstrom a year ago and their common interests led to the collaboration. "Jon is one of the leaders in the molecular pharmacology of nicotinic receptors, and has been for many years," Kenny said. "Our work is complementary - he approaches the problem from the bottom up, starting at the receptor. We approach the problem from the top down, starting from a behavioral perspective."
Kenny said that he plans to use Scripps Florida's compound screening resources to look for compounds that Lindstrom can then test to provide a clearer understanding of how they work on the receptor subunits. The researchers then hope to conduct further studies on the effectiveness of the most promising compounds.
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