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Modified Drug Therapy for Alzheimers Disease

Purdue university researchers has found a new modified drug for Alzheimers disease.The drug has begun the first phase of clinical trials.

Millions of people suffer from this devastating disease and treatment options are very limited," said Arun Ghosh, the Purdue professor who led the creation of the treatment molecule. "Current drugs manage the symptoms, but this could be the first disease-modifying therapy. It may be able to prevent and reverse the disease."

CoMentis Inc., a biopharmaceutical company based in San Francisco, is initiating the clinical trials of the experimental drug CTS-21166. Ghosh, who has dual appointments in the departments of chemistry and medicinal chemistry, is a scientific co-founder of the company with Jordan Tang, the J.G. Puterbaugh Chair in Medical Research at the Oklahoma Medical Research Foundation.

The collaborative work of Ghosh and Tang led to the development of a treatment that could intercept and disable the disease at an early stage.In 2000, Tang identified beta-secretase, a key enzyme in the progression of Alzheimer's that triggers the formation of amyloid plaques in the brain.

Various stages in plaque formation produce toxic proteins that harm the brain, causing damage that eventually leads to dementia. Later that year, Ghosh built a molecule that binds to this key enzyme and inhibits its activity, a beta-secretase inhibitor.

X-ray crystal structureDownload photo caption below These molecules fit together like puzzle pieces," Ghosh said. "We created a molecule that fits with a key piece of the Alzheimer's disease puzzle. When the treatment molecule binds to the enzyme, it changes the shape of that puzzle piece so that it no longer fits in its original spot. This halts the chain reaction that leads to the devastating symptoms of Alzheimer's disease."

Since 2000, Ghosh has been leading the structure-based design of beta-secreatase inhibitors f or therapeutic intervention of Alzheimer's disease. His most recent work was published in the May 17 issue of the Journal of Medicinal Chemistry.

Ghosh also helped direct CoMentis in the generation of beta-secretase inhibitor drugs. The treatment molecule, beta-secretase inhibitor CTS-21166, is the culmination of this work.

"The molecule is both highly potent and highly selective, meaning it does not appear to affect other enzymes important to brain function or cause harmful side effects," Ghosh said. "It took years of work and evaluation of hundreds of molecules to achieve one with the strength and safety necessary for clinical potential."

The trial, comprised of 48 healthy volunteers, will measure safety, tolerability and pharmacokinetics of CTS-21166 at various doses. The company expects to begin generating human clinical data by the end of 2007 and to begin phase II studies in Alzheimer's patients in 2008. The drug could be administered at any stage of the disease, Ghosh said.

These clinical trial phases are the first steps in a lengthy process necessary before the Food and Drug Administration approves a drug to be available on the market.




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