Where are the new drugs?  pg. 5

The discovery, reported in 2005 in the journal Nature Neuroscience, could lead to new ways to treat conditions as diverse as pain and diabetes.

Hamm admits that G protein “therapy” is unlikely to attract major drug company investment—at least not yet. So several years ago, about the time she was moving from Northwestern University to Vanderbilt, she and her colleagues formed their own drug discovery company in Evanston, called cue BIOtech.

They chose to study a receptor embedded in the membrane of clot-forming platelets that binds the coagulation factor thrombin.

Blood clotting is essential for wound healing, but too much thrombin in the wrong place can trigger a heart attack. Blood-thinning drugs like Coumadin can prevent platelets from forming clots, but—unless the dose is carefully monitored—they can cause uncontrollable bleeding.

It has been difficult to block thrombin, which actually is an enzyme that activates its receptor by chopping it in half. So Hamm and her colleagues are trying to tackle the problem from inside the cell, by blocking receptor action instead of receptor binding.

So far they’ve been able to make “very potent” small molecules that prevent the thrombin receptor from binding to or activating its G protein. “In cells—we haven’t gotten to animals yet—they do exactly what we want them to do,” she says. “They’re inhibitors of platelet aggregation.”

Drug companies are still skeptical, but now at least Hamm’s idea doesn’t seem so pie in the sky.

The role of government

The onerously high cost of making new drugs has not escaped the attention of federal health officials.

In a 2004 report entitled “Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products,” the U.S. Food and Drug Administration called for increased public-private collaboration to boost drug development through the application of new technologies.

“We must modernize the critical development path that leads from scientific discovery to the patient,” the report urged.

Developing new tools to aid drug discovery also is the goal of the Molecular Libraries Screening Center Network, established in 2004 by the National Institutes of Health as part of its Roadmap initiative to help translate new scientific knowledge into “tangible benefits for people.”

The aim is harness the fruits of the genomic revolution, make them available to scientists in universities and industry alike, and encourage them to work together as never before, explains Christopher Austin, M.D., senior advisor for translational research at the National Human Genome Research Institute.

“What we hope to do… is the high capital investment… take the assay, do the robotic screening on a big library, do some initial chemistry, and give (scientists) back a small molecule compound which allows them to query the function of that gene or pathway—to test a hypothesis,” Austin says.

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