Pre-clinical Development of a Vaccine Against Alpha-synuclein Based on Virus-like Particles

Objective/Rationale:             
Overexpression of the protein alpha-synuclein has been identified as a major cause for the development of Parkinson’s disease (PD) in humans. Lewy bodies, which consist mainly of aggregated alpha-synuclein, are a histological hallmark of the disease. It has recently become evident in pre-clinical models of PD that antibodies specific for alpha-synuclein may delay or even halt disease progression. We plan to induce production of such antibodies by vaccination.

Project Description:             
Here we will develop a vaccine against alpha-synuclein in a novel pre-clinical model of PD. To optimize immune and antibody responses, virus-like particles (VLPs) will be used to display full-length alpha-synuclein or smaller peptides. Vaccine candidates will be designed to induce antibodies recognizing all potentially toxic forms of alpha-synuclein, i.e. soluble, oligomeric and aggregated alpha-synuclein.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:                     
If the pre-clinical experiments can be concluded successfully, we will proceed to Phase I/II clinical trials in Parkinson’s patients. The ability to reduce alpha-synuclein levels could serve as a disease-modifying treatment to slow or halt PD progression.

Anticipated Outcome:          
Use of VLP-based vaccines has documented ability to induce strong and clinically relevant levels of self-specific antibodies in animals as well as humans. This is different from most other platforms where strong adjuvants not compatible with use in humans are employed for pre-clinical experiments resulting in failure to translate these observations from models to clinical efficacy in humans. We expect that the experiments performed will show efficacy of this vaccine approach, enabling us to enter clinical development.