Morphology specific anti-synuclein nanobodies as therapeutics for PD

Project: Research project

Project Details


Morphology specific anti-synuclein nanobodies as therapeutics for PD Morphology specific anti-synuclein nanobodies as therapeutics for PD Protein misfolding, aggregation and deposition is a common thread in numerous neurodegenerative disorders including Alzheimer's Disease, Huntington's Disease and Parkinson's Disease (PD). Aggregation and deposition of the protein, a-synuclein (a-syn), has been strongly correlated with PD and other related neurodegenerative disorders The a-syn protein occurs in a variety of forms and complexes all of which can aggregate into different morphologies including various toxic oligomeric species. We have developed unique capabilities that enable us to generate conformation specific single-chain Fv (scFv) antibodies that target specific protein morphologies and to test their function in vitro and in vivo. We have extensive experience in testing immuntherapeutics in animal models of neurodegenerative disease. Here we will determine which morphology specific scFv constructs are the most effective therapeutic agents using the mThy1.2- a-synuclein transgenic mouse model of PD. In preliminary studies, we have shown that anti-a-syn antibodies can cross the blood brain barrier and reduce a-syn levels in the brain providing therapeutic benefit. We will study two variants of each scFv, one traditional extracellular version and one designed to penetrate cells to determine whether targeting extracellular or intracellular a-syn aggregates is the most effective therapeutic strategy. The collaborative team assembled for this proposal has unique capabilities to study the role of asyn aggregation in PD. Dr. Michael Sierks (ASU) has pioneered the development of conformation specific scFv reagents while Dr. Eliezer Masliah (UCSD) is a leading expert in immunization studies in animal models of PD.
Effective start/end date11/1/105/16/13


  • Michael J. Fox Foundation: $552,273.00


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