Effect of HDAC Inhibition in Models of Parkinson's Disease
Therapeutic Pipeline Program, 2016
Numerous publications have linked the family of epigenetic enzymes known as HDACs (histone deactylases) to the underlying pathology of Parkinson's. This study will test the efficacy of Rodin's selective HDAC inhibitors in improving the impaired motor dysfunction in two models of Parkinson's disease (PD). These compounds may also have impact on cognitive dysfunction associated with PD.
Specific HDAC inhibitors will improve brain pathology and symptoms in two models of Parkinson's disease, and these results will be used to support the case for testing in clinical trials in humans.
Two models of Parkinson's will be used to test Rodin's HDAC inhibitors: the MPTP model, which uses a chemical toxin that results in Parkinson's pathology, and a transgenic model known as the A53T synuclein model, which overexpresses a toxic form of a key protein linked to Parkinson's. In both cases, the models will be treated for 14 days with Rodin HDAC inhibitors in an attempt to stabilize or improve symptoms in the mice. Brain sections will be analyzed for expression of key molecules and levels of gene expression to understand the underlying mechanism of the drug's actions.
Impact on Diagnosis/Treatment of Parkinson's Disease:
We are attempting to develop drugs that take a new approach to improving the symptoms and underlying damage that has occurred in Parkinson's patient's brains.
Next Steps for Development:
If this study is successful, we will test the HDAC inhibitor compounds further in these and/or other models of Parkinson's disease to help pick the best compounds as clinical candidates. We will then perform the requisite safety and related studies to move the chosen compounds forward toward clinical trials in humans.
Senior Director of CNS Research at Rodin Therapeutics
Location: Cambridge, Massachusetts