FEATURE ARTICLE
Alzheimer's Disease
The molecular origins of the disease are coming to light, suggesting several novel therapies
Vernon Ingram
Removing Aggregates with Antibodies
Another approach to interrupting the disease harnesses the patient's immune system to identify and remove the toxic Aβ1-42 aggregates. In principle this can be done either by active or by passive immunization. In the former case, the patient receives an injection or nasal-spray application of the Aβ peptide, leading to an anti-amyloid immune response. Both injection and spray strategies are being pursued, and clinical trails have begun. Passive immunization bypasses the beta amyloid protein, using instead antiserum that has already been produced in response to beta amyloid. This is also being pursued actively.
Part of the excitement about immunotherapy was based on successful animal studies, including one using transgenic mice engineered to overexpress human APP sequence. As described by Dennis Selkoe of Harvard and Dale Schenk with Elan Pharmaceuticals, the mice showed a strong immune response to the Aβ peptide, leading to a substantial reduction in the accumulation of beta protein and a partial elimination of memory deficits.
Such results held great promise for the future of this therapeutic approach. Unfortunately, the anticipation has sharpened recent disappointment over the termination of a large, international clinical trial. About five percent of 375 patients enrolled in the trial developed severe brain swelling after being inoculated with the Aβ peptide. This inflammation could have been due to a mistake in exactly which part of Aβ to use, or perhaps the peptide needed to be refined more cautiously, or the immunization procedure itself may need to be altered. However, other trials using other protocols are proceeding, and the results are eagerly awaited. Clinical trials of passive immunization have also begun, but the study authors have not yet published results. Passive immunization requires a continuing regimen of injections of the antiserum preparation, a feature that had been seen as a disadvantage but may yet prove superior if it bypasses the complications of Aβ inoculation.
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