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Apr 18, 2007

Scientists Create Molecule to Inhibit Alzheimer’s Pathway

  • A Purdue University researcher says that he has designed a molecule that could lead to the first drug treatment for Alzheimer's disease. The new molecule prevents the first step in a chain of events that leads to amyloid plaque formation in the brain. 

    Arun Ghosh, Ph.D., professor at Purdue,  used research done by Jordan Tang, Ph.D., on an enzyme involved in the development of Alzheimer's disease. Dr. Tang, head of the protein studies research program at the Oklahoma Medical Research Foundation discovered memapsin 2, beta-secretase. He found that the action of this enzyme on the amyloid precursor protein leads to the formation of plaques in the brain.

    Research into memapsin 2 faced a setback when memapsin 1, an enzyme similar in structure, was discovered. Unlike memapsin 2, memapsin 1 is involved in many important biological processes and its inhibition would cause serious adverse side effects.

    Dr. Ghosh designed the first memapsin 2 inhibitor. He used X-ray crystallography to map the structure of the designed inhibitor bound to the enzyme. This revealed information necessary to develop molecules that could be used in drugs and specifically target memapsin 2.

    "The moment we had the crystal structure, we knew exactly how the inhibitor worked, the interactions of the molecular bonds, and what properties were most important," says Dr. Ghosh. "This allowed us to quickly build inhibitor molecules and bypass the usual lengthy process of trial and error in molecule design."

    "In our most recent tests, a single dose of the designed compound reduced the beta-amyloid level by 30%," reports Dr. Tang.

    Dr. Ghosh and Dr. Tang founded the biopharmaceutical company Zapaq,  which has merged with CoMentis.  CoMentis will use the research results to begin to develop pharmaceuticals. A drug from the memapsin 2 inhibitor could go into Phase I trials this year, they say.

    The results of this study will be published in the May 3 issue of Medicinal Chemistry.



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