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2006 Grant - Jankowsky
Combination Therapy for the Treatment of Alzheimer's Disease
Joanna L. Jankowsky, Ph.D.
California Institute of Technology
2006 New Investigator Research Grant
Amyloid plaques in the brain are one of the characteristic features of Alzheimer pathology. The primary component of these plaques is the protein fragment beta-amyloid, which has toxic effects on nerve cells. Because beta-amyloid appears to play a key role in Alzheimer's disease, numerous therapeutic strategies have been proposed that involve removal of beta-amyloid or prevention of its formation.
One strategy for removal of beta-amyloid involves the use of antibodies that recognize the protein fragment and target it for removal by the immune system. Early tests have found that this strategy may successfully remove beta-amyloid, but it may cause some intolerable side effects. Furthermore, this strategy will not prevent the formation of new amyloid plaques unless the antibodies are administered regularly.
A leading strategy for preventing the formation of beta-amyloid is the use of drugs that inhibit the enzymes that produce it. Beta-amyloid is produced from a parent protein, amyloid precursor protein (APP), by the cutting activity of enzymes known as secretases. Drugs that inhibit the secretases prevent the formation of beta-amyloid. However, they cannot remove existing plaques.
Joanna L. Jankowsky, Ph.D., and colleagues have proposed combining these two treatment strategies to take advantage of the positive qualities of each. This approach will utilize a short-term treatment with an anti-beta-amyloid antibody to remove existing plaques, in combination with long-term treatment using a drug to inhibit secretase activity. The researchers plan to test the efficacy and safety of this approach using genetically altered mice that develop an Alzheimer-like disorder.