Building antibodies against specific forms of Abeta

Michael Sierks, PhD
Arizona State University (Tempe, AZ)
Year Awarded:
2007
Grant Duration:
March 31, 2007 to March 30, 2009
Disease:
Alzheimer's Disease
Award Amount:
$150,000
Grant Reference ID:
A2007134
Award Type:
Pilot
Award Region:
US Southwestern

Morphology Specific Antibodies to Beta-Amyloid

Summary

The hypothesis of this proposal is that highly specific and well defined scFvs to specific oligomeric morphologies of Aß can be isolated by useful therapeutics for treating AD. The long term goal is to use the pool of morphology specific scFvs to probe the roles of the various Aß morphologies in AD and to test the value of these scFvs as potential diagnostic and therapeutic agents.

Details


Alzheimer's Disease (AD) is characterized by the presence of neuritic plaques and neurofibrillary tangles. The role of Aß in AD is still controversial, an issue that has been complicated greatly by the multiple lengths and morphologies of Aß. A wealth of literature suggests the various lengths and morphologies have different effects on neuron viability and memory. In order to reliably assess the roles of Aß and anti-Aß vaccination strategies in AD, highly specific and very well-defined reagents such as single chain antibody binding variable domains (scFvs) that target individual Aß forms and morphologies are needed. Using a novel technology combining antibody diversity and microscopic imaging techniques, scFvs against specific Aß morphologies can be isolated. The isolated scFvs can be affinity matured to have extremely high specificity for the target ligands. The hypothesis of this proposal is that highly specific and well defined scFvs to specific oligomeric morphologies of Aß can be isolated by useful therapeutics for treating AD. The long term goal is to use the pool of morphology specific scFvs to probe the roles of the various Aß morphologies in AD and to test the value of these scFvs as potential diagnostic and therapeutic agents.

Publications

Zameer, A.; Rangan, SK., Emadi, S.; Nimmagadda, S. and Sierks, MR. Anti-oligomeric Abeta single chain variable domain antibody blocks Abeta induced toxicity against human neuroblastoma cells. J Mol Biol. 384, 917-28 (2008).  

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