Objective/Rationale:
Progressive loss of dopamine neurons and clumps of the protein alpha-synuclein are hallmarks of Parkinson’s disease (PD). Intrabodies are small antibody fragments that target antigens (any substance that triggers an immune response). This characteristic may be exploited to target alpha-synuclein clumps. We propose to demonstrate the neuroprotective properties of two intrabodies targeting different regions of alpha-synuclein in a pre-clinical model of PD.
Project Description:
Models will be injected with alpha-synuclein then intrabodies in the substantia nigra region of the brain. We will carry out behavioral tests to evaluate the models’ motor function. Brain will be processed to determine the number of dopamine neurons, dopamine levels and alpha-synuclein present in the substantia nigra. These will be compared to normal control levels to determine the extent of neuroprotection/modulation.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Intrabodies may help avoid or break up alpha-synuclein accumulation and thereby treat Parkinson’s disease by protecting dopamine neurons.
Anticipated Outcome:
Testing the application of these intrabodies in PD models will help take the intrabody technology to the next step in translational research and closer to its use as a potential intervention for PD.