Objective/Rationale:
This three-year collaborative project between three seasoned Parkinson’s disease (PD) investigators capitalizes on their extensive PD research experience and new understanding of the cell-to-cell spread of PD pathology in pre-clinical and non-human model systems. They will also call on one of the largest published anti-alpha-synuclein monoclonal antibody (MAb) libraries to identify the most promising MAbs so two to three MAbs can be advanced to human clinical trials in patients with PD and/or PD with dementia (PDD).
Project Description:
We have seen recent dramatic advances in understanding how the progression of PD, including progression to PDD, is linked to the transmission or cell-to-cell spread of alpha-synuclin pathology, the signature lesion that defines PD. These finding have created new opportunities to develop antibody-based, disease-modifying immune therapy for patients with PD/PDD. This collaboration will exploit these new insights and harness the researchers’ collective expertise to screen MAbs from one of the largest anti-alpha-synuclein MAb libraries. We will identify the two or three most promising MAbs in novel pre-clinical model systems based upon alpha-synuclein transfer, so they can be advanced to human clinical trials in patients with PD and/or PDD with a pharmaceutical company partner.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
This project addresses one of the greatest unmet needs for PD/PDD patients, which is to develop effective disease-modifying therapies that will arrest or slow progression of PD/PDD. Based on the rapid advance of immune therapy for Alzheimer’s disease (AD) from pre-clinical studies to clinical trials in AD patients, one can anticipate a similar rapid advance for the therapeutic approach described here to testing anti-alpha-synuclein MAbs in human clinical trials.
Anticipated Outcome:
The goal is to identify the two to three most promising anti-alpha-synuclein MAbs in pre-clinical model systems so they can be advanced to human clinical trials in patients with PD and/or PDD at the conclusion of the three-year project with a pharmaceutical company partner.