Identification of ASC as a Disease-modifying Therapeutic Target in Parkinson’s Disease

Study Rationale:
Inflammasomes are large multiprotein complexes that play a central role in the innate immune system, the body’s first line of defense against microbes. Inflammasomes are key drivers of inflammation that are widely implicated in propagating neuron death in neurodegenerative diseases such as Parkinson’s disease. Our prior studies have shown that a key protein in the inflammasome, called apoptosis-associated speck-like protein containing a CARD (ASC), is increased in Parkinson’s disease patients, and in experimental models. Pre-clinical models genetically deficient in ASC have reduced severity of disease, suggesting this protein could be a key target for therapeutic intervention.

Hypothesis:
We hypothesize that specifically inhibiting ASC will slow the progression of disease in pre-clinical models of Parkinson’s disease.

Study Design:
We will first investigate the effect of targeted genetic therapeutic inhibition of ASC in two distinct pre-clinical Parkinson’s disease models. We will then test whether this therapeutic approach also shows beneficial activity when administered after the onset of symptoms in these models.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
Our studies will identify if ASC plays a key role in neuron death in experimental models of Parkinson’s disease. It will also identify if administering a drug which inhibits ASC can slow the progression of disease, which could lead to the development of new treatment.

Next Steps for Development:
The results from this study will help inform if ASC is a viable therapeutic target for Parkinson’s disease.