We recently demonstrated that strong immune system stimulation created by treating pre-clinical models with a safe vaccine (called BCG) can have a restorative effect on nigrostriatal dopamine system integrity and limit potentially deleterious microglial responses to MPTP exposure. The goal of this proposal is to generate pre-clinical data that can be used as a justification for consideration of a BCG vaccination trial in newly diagnosed Parkinson’s disease (PD) patients.
Using the MPTP pre-clinical model, we will 1) optimize BCG vaccination parameters and 2) determine the neurorestorative capacity of BCG vaccination after the administration of MPTP. In parallel studies, we will determine whether BCG vaccination has a beneficial effect in transgenic pre-clinical models that overexpress human alpha-synuclein in neurons and which model other aspects of Parkinson’s disease.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Immune stimulation is a heretofore untested adjunct therapeutic strategy for PD. While BCG-induced immune responses cannot correct basic intrinsic neuronal deficits, they may alter the CNS environment to be more neurosupportive so that neurodegeneration and secondary damage to neurons progresses at a slower rate.
We anticipate that the results of this 2-year proposal will provide sufficient positive pre-clinical data to consider a BCG vaccine futility study in humans, similar to that used by the NINDS Neuroprotective Exploratory Trials in Parkinson’s Disease Program.
In the MPTP pre-clinical model, we found a positive correlation between the number of regulatory T
cells (Tregs) induced by vaccination with BCG, and the preservation of striatal DA and DAT. In the α-SYN model, several types of locomotor deficits were reduced by a single BCG vaccination.
Thus, in two different pre-clinicalmodels of Parkinson’s disease, we observed that BCG immunization had a beneficial effect. Given BCG’s superb safety record, our findings provide compelling evidence supporting the notion of testing BCG in clinical trials with Parkinson’s patients.