Liver X Receptor Agonists as Novel Therapeutics for Parkinsonís Disease
Therapeutic Pipeline Program, 2014
Study Rationale: † † † † † † † † ††
Inflammation is an early and characteristic feature of Parkinsonís disease. Recent studies connect a protein called the liver X receptor (LXR) to inflammation in key tissues in the brain. Recent studies in pre-clinical models of Parkinsonís disease show that molecules that activate the LXR protein reduce dopamingeric neuron loss. Based on these data, we plan to identify a drug candidate that is effective without side effects in models of Parkinsonís disease.
The therapeutic being developed is a small-molecule LXR activator that is selective or specific for the LXRb isoform. It is believed that toxic effects seen with LXR activation are mediated via the LXRa isoform, which is expressed in the liver. As such, a LXRb-selective molecule should have efficacy in the brain ó where LXRb is the dominant isoform ó without liver-mediated toxic effects.
We will make and test LXR activators in appropriate biological assays (experimental tests) to target LXRb selectivity.
Impact on Diagnosis/Treatment of Parkinsonís Disease: † † † † † ††
This project offers a coordinated and novel approach to disease modification.
Next Steps for Development:
If the current program is successful, we will next advance our drug candidate(s) into extended pre-clinical studies to show (a) beneficial effects on disease pathology and (b) no adverse safety profile on longer-term dosing.
Executive Vice President of Research at Alexar Therapeutics, Inc.
Location: Malvern, Pennsylvania, United States