I asked my colleague Kuldip to share some insights and below are his contributions.... Debi



Let me provide you with some more relevant information around the work we are doing regarding the topics being discussed here. First of all, we should be very cautious in calling PD a prion disorder. Infectiousness is a central hallmark for prion disorders. However, it has never been reported or documented in PD patients. Even clinically, a prion disease such as Creutzfeld-Jakob disease (CJD) is very different from PD. CJD, once it manifests, has a rapidly progressing phase over a period of few months whereas PD is a slow progressive disease with a time frame of years and decades to develop. The brain pathology also looks vastly different in that spongiform encephalopathy is observed in CJD (and not in PD) and Lewy bodies are observed in PD (and not in CJD).

A few similarities do exist as to how PrP protein (involved in prion diseases) and alpha synuclein protein (involved in PD) may behave at the molecular level. Both of these proteins have the ability to misfold and aggregate. Pathology resulting from aggregation of these proteins has been shown to spread from cell to cell in animal models. Although these similarities exist in the way the two proteins behave, the mechanism by which the pathology spreads from cell to cell is not fully understood. It is also not fully understood whether the spreading of alpha synuclein pathology seen in a test tube or an animal brain has any direct relevance or link to the human PD pathology (as in what’s happening in “real” life)!

MJFF is currently funding studies to define further how alpha synuclein spreads, understand the mechanism by which it is doing so, trying to see if we can use alpha synuclein’s “spreading” phenomenon as a potential biomarker and finally funding therapeutic approaches that may try to leverage blocking this spread as a way to modify PD disease progression.

With regards to drugs that fall into the “anti-organ rejection” category, MJFF has funded research both validating the targets as well as therapeutic development in this area. For example, we funded to determine if FKBP reduction (one way by which anti organ rejection drugs work) would work as a proof of concept and the study showed that it worked positively in preclinical experiments. The main challenge in repurposing “anti-organ rejection” drugs for PD has been side-effects such as immunosuppression. Use of such drugs for a shorter duration (months) for organ rejection versus giving it chronically to Parkinson’s patients (for years) has to be explored.

We continue to monitor the field to identify gaps in research and fund field-enabling and critical experiments to understand the disease and find a cure.

Kuldip Dave, Ph.D.
Director, Research Programs