Feuerstein's Biotech Mailbag

Beta-amyloid immunotherapy attempts to treat Alzheimer's by inducing or enhancing a person's own immune system to clear beta-amyloid from the brain. Immunotherapy can take two basic approaches: Active immunization stimulates the body's own immune system to manufacture beta-amyloid antibodies that recognize the substance as foreign, attack it and clear it from the brain. The alternative approach is passive immunotherapy, whereby a synthetically manufactured antibody is injected into the body, seeks out and attaches to beta-amyloid and clears it from the brain.

AAB-001 takes the latter, passive, approach. The drug is a monoclonal antibody designed to recognize and attach itself to a specific portion (the N terminus) of the beta-amyloid protein. Once attached, beta-amyloid fragments are sequestered and cleared from the brain by glial cells, non-neuron support cells in the brain. Only a very small amount of AAB-001 appears to penetrate the blood-brain barrier (a possible red flag). But AAB-001 also appears to work outside the brain, in the peripheral circulation, which may mean that it prevents beta-amyloid from getting into the brain.

Elan and Wyeth are also working together on an active immunotherapy approach to treating Alzheimer's. The two companies have another compound known as ACC-001 in a Phase 1 trial. And separately, the two companies are active in the field. Elan recently partnered with Canadian-based Transition Therapeutics (TTH.TO) to develop a drug called AZD-103.

Eli Lilly (LLY) is also developing a monoclonal antibody targeting beta-amyloid. The drug, M266, recently started a Phase 2a study. This drug appears to be similar to AAB-001, with the major difference being that it's designed to attach itself to a different part of the beta-amyloid protein.

Pfizer(PFE) is also getting involved in this area via its April 2006 acquisition of privately held biotech firm Rinat BioScience. One of the drugs under development at Rinat is RN1219, also a monoclonal antibody (humanized) that targets beta-amyloid clearance. RN1219 is still in preclinical testing.

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