Objective/Rationale:
Erythropoietin (EPO) receptor is present throughout the body and plays a role in both red blood cell production and tissue protection. STATegics has discovered small molecule EPO receptor agonists (EPORA) that are selective for neuroprotection and demonstrate bioavailability in the brain tissue. The compounds offer potential as candidate therapeutics for Parkinson’s disease (PD). The goal of this research program is to demonstrate drug-like properties and a proof-of-concept for the efficacy of the compounds in protecting dopaminergic neurons in pre-clinical models of PD.
Project Description:
Small molecule EPORA compounds have demonstrated promising properties as candidate therapeutics for PD in pre-clinical studies. Our prior experiments illustrate direct activation of the tissue-protective EPO receptor, neuroprotection, favorable safety profile, and penetrance of the small molecules to the brain at pharmacologically relevant concentrations. As part of this research program, we will scale up the synthesis of the compounds, further characterize the neuroprotective activities in cell culture, and evaluate the compounds’ efficacy in protecting dopaminergic neurons in pre-clinical studies. The studies will be carried out in collaboration with Prof. Timothy J. Collier at Michigan State University. A clinical candidate will be selected based on a combination of results from the experiments in cell culture, pharmacokinetics and efficacy in a pre-clinical model of PD.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Neuroprotective small molecule EPORA compounds are hypothesized to protect against the ongoing loss of dopaminergic neurons in PD. Based on prior reports on EPO receptor biology, the compounds may also support the treatment of depression and cognitive dysfunction that associate with PD. EPORA compounds may slow down the progression of the disease and may also offer the potential to repair some of the damaged brain tissue acting as disease modifying therapies.
Anticipated Outcome:
Successful completion of these studies is expected to demonstrate the drug-like properties and pre-clinical efficacy of EPORA compounds. The studies are designed such that a candidate therapeutic could be selected for more detailed development at the end of the program. Following the completion of the studies proposed here, the overall goal is to advance the selected compound into clinical studies in patients with PD.
PARTNERING PROGRAM
This grant was selected by The Michael J. Fox Foundation staff to be highlighted via the Foundation’s Partnering Program.
