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Antibody Treatment
Two new studies, both released in October 20044, suggest that new treatment options may be on
horizon. The studies are modification of one of two previous attempts using amyloid beta (Aβ) antibodies in treatment of Alzheimer’s Disease. The previous attempts, though not successful, did at least suggest new courses of action in Alzheimer’s research and provided invaluable information for researchers.
In first of two previous attempts, researchers injected antigen itself – pieces of beta amyloid protein that makes up amyloid plaque – into mice, in hopes that injections would generate an immune (antibody) response against amyloid. Results were initially positive. The injected antigen produced Aβ antibodies and slowed onset of disease by decreasing Aβ levels. However, when tried on humans, procedure led to meningoencephalitis (an inflammation of tissue around brain) in some patients, and was therefore halted.
In second attempt, a passive immunity therapy was tried in which antibodies to amyloid beta (not amyloid protein) were injected into mice, but hemorrhaging and inflammation ensued due to high antibody doses required to be effective.
New Hope
But now there appears to be new hope for use of antibodies as therapeutic agents for treatment of Alzheimer’s patients. In first of two new studies that appeared in October conducted by National Institute for Longevity Sciences, NCGG, and Center for Neurological Diseases, Brigham & Women’s College, Harvard Institute of Medicine, researchers modified first procedure. Concluding that meningoenchaphalitis which occurred in some patients was caused by autoimmune T-cell activation, researchers hoped to develop a vaccine that could minimize this T-cell activation while retaining production of Aß antibodies. To accomplish this they created an oral vaccine that attached Aß DNA to an adeno-associated virus vector, which served to mitigate T-cell activation. Thus they were able to decrease Aß levels in brains of mice and yet not activate T-cells to degree they had before, greatly reducing risk of meningoencephalitis.
In other new study, conducted at University of Illinois at Chicago, researchers succeeded in making passive immunity protocol much safer. This they accomplished by changing point of entry for Aß antibodies. Rather than injecting antibodies into body of mice, as was done previously, antibody was injected directly into brain of mice. Because antibodies were injected directly into brain, smaller doses were needed, and side effects were minimized.
The results of above studies, and potential for further optimized immunization strategies may prove to be watershed events in history of Alzheimer’s treatment.
Covance is a leading provider of innovative antibody products and custom antibody development services to research community for Alzheimer’s disease. Visit www.Covance.com for more in-depth information and to view suite of products for Alzheimer’s disease. Boris Predovich is Vice President of Immunology and Surgical Services at Covance Research Products.
Notes
1.J.A. Hardy, G.A. Higgins (1992), Science, 256:184-5. 2.M.P. Lambert et al (1998), Proc Natl Acad Sci, 95:6448-53. 3.D.M. Walsh et al (2002), Nature, 416:535-9. 4.Neelima B. Chauhan et al (2004), Journal of Neuroscience Research, 78, 5:732-741. Hideo Hara et al (2004), Journal of Alzheimer’s Disease, 6, 5:483-488.
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