Evaluation of PARIS ASOs in Models of Parkinson's Disease

Study Rationale:
The parkin-interacting substrate (PARIS) prevents genes that are important in the survival of dopamine neurons from working by limiting their expression in neurons. Previously we showed in models of Parkinson's disease that (i) there is substantial accumulation of PARIS that leads to loss of dopamine neurons and (ii) this can be prevented by genetic deletion of PARIS.

Hypothesis:
We propose that synthetic polymers called anti-sense oligonucleotides (ASOs) will lower levels of PARIS.

Study Design:
We will test if PARIS ASOs will lower the levels of PARIS in laboratory models of Parkinson's disease, thereby preventing the degeneration of dopamine neurons.

Impact on Diagnosis/Treatment of Parkinson's Disease:
If the ASOs were successful in our models of Parkinson's disease, it could lead to the development of strategies to inhibit the actions of PARIS as a new treatment for Parkinson's disease.

Next Steps for Development:
If the ASOs were successful in our models of Parkinson's disease, we would work to develop human PARIS ASOs. That would hopefully to lead to investigational trials of PARIS ASOs in people with Parkinson's disease.