The Transfer of Alpha-Synuclein: Mechanistic and Therapeutic Studies
Research Grant, 2012
The research from this grant has continued with the supplementary grant:
This three-year collaborative project between three seasoned Parkinsonís 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).
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 researchersí 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 Parkinsonís 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 Alzheimerís 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.
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.†
The Jean Schweppe-Armour Professor of Neurological Sciences and Professor of Neurosurgery at Rush University Medical Center
Director of the Research Center for Brain Repair and Neuroscience Section Head at Rush University Medical Center
Location: Chicago, Illinois, United States
Professor, Center for Neurodegenerative Research at University of Pennsylvania, School of Medicine