Parkinson's Disease Vaccine Programme
Programme Leader: Prof Martin Bachmann, Jenner Institute, University of Oxford
Parkinson’s disease is a progressing and devastating illness caused by a loss of dopamine-producing neurons in the brain. Currently, there is no therapy with lasting efficacy.
Overexpression of alpha-synuclein has been identified as a major cause of the development of Parkinson’s disease (PD) in humans. As little as a 1.5 or 2-fold upregulation of alpha-synuclein can cause familial PD (Singleton et al Science. 2003 (PMID 14593171), Chartier-Harlin et al Lancet. 2004 PMID 15451224).
Lewy bodies, consisting mainly of aggregated alpha-synuclein, are a histological hallmark of the disease. However, it is unclear whether these large alpha-synuclein aggregates are responsible for the pathology or whether small alpha-synuclein oligomers may also be toxic and cause disease (Conway et al Proc Natl Acad Sci U S A. 2000 PMID: 10639120).
Therapies based on antibodies against alpha-synuclein should therefore preferably employ antibodies of broad specificity able to recognize soluble, oligomeric as well as aggregated alpha-synuclein.
To develop a vaccine against Parkinson’s, we will use virus-like particles (VLPs) displaying alpha-synuclein, or fragments derived from alpha-synuclein, on their surface.
Use of VLP-based vaccines has repeatedly documented an ability to induce strong and clinically relevant levels of self-specific antibodies in preclinical models and clinical studies. This is different from most other platforms where strong adjuvants not compatible with use in humans are employed for preclinical experiments resulting in failure to translate these observations from animals to clinical efficacy in humans.
The challenge now is to ensure we identify and target the more relevant pathogenic species to reduce or even prevent the progression of these debilitating neurodegenerative diseases.
If the preclinical experiments can be concluded successfully, we will proceed to Phase I/II clinical trials in Parkinson’s patients