Where are the new drugs?  pg. 2

Toward that end, the VICB in 2005 opened a high-throughput screening facility to help search for small molecules (a class of organic chemicals) with drug-like activity. Vanderbilt also has signed a master research agreement with biotechnology giant Amgen to conduct an array of collaborative research projects.

The intent of these efforts is to encourage Vanderbilt researchers to pursue the therapeutic potential of their discoveries.

Discovering a potential drug target is not enough, explains Jeffrey Conn, Ph.D., director of the Vanderbilt Program in Drug Discovery. If academic scientists took the next steps—identifying a compound that acted on the target, and conducting the laboratory and animal tests necessary to validate its therapeutic potential—you can then justify a company really locking into a full-scale drug discovery program, he contends.

Jennifer Washburn, author of University, Inc., is more than skeptical. In the February 2005 issue of The American Prospect magazine, she wrote: “Instead of honoring their traditional commitment to teaching, disinterested research, and the broad dissemination of knowledge, universities are aggressively striving to become research arms of private industry.”

Gordon R. Bernard, M.D., assistant vice chancellor for Research at Vanderbilt, disputes that contention.

While collaborations with industry can result in conflicts of interest, many universities, including Vanderbilt, have implemented procedural and contractual safeguards to identify and manage such conflicts. These safeguards protect the academic mission while permitting opportunities to transfer new information and technologies for the benefit of society, he says.

Marnett agrees. “We are not going to be drug companies. But we can advance the field,” he says. We can identify new therapeutic concepts, new drug-design concepts. That’s what we should be doing.”

Turn up the light

Where will the new drugs come from?

One area to watch: G protein-coupled receptors (GPCRs).

GPCRs are embedded in the membranes of nearly every cell and are the most common conduit for signaling pathways found in nature.

Two-thirds of all drugs target these receptors. The beta-blocker drug propranolol lowers blood pressure by preventing adrenaline from binding to its GPCR. Drugs that are given to relieve symptoms of Parkinson’s disease act through a GPCR that binds dopamine.

Parkinson’s disease illustrates the complexity of the signaling pathways that utilize GPCRs. Characterized by tremors, difficulty walking and muscle weakness, the disease is caused by the progressive loss of dopamine-producing nerve cells and the resulting lack of dopamine, a neurotransmitter involved in the coordination of muscle movement.

Current dopamine replacement therapy squelches the tremors and improves coordination, but prolonged use of the drugs can cause significant side effects, including involuntary muscle movements and hallucinations, and the medications become less effective as the disease progresses.

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