Pre-clinical Evaluation of Neuroprotective Small Molecule Erythropoietin Receptor Agonists in the Treatment of Parkinson’s Disease Supplement

Study Rationale:                   
STATegics has discovered small molecules that selectively activate the tissue-protective erythropoietin (EPO) receptor, but not the EPO receptor that plays a role in red blood cell production. In previous studies, the lead compound demonstrated potent neuroprotective effects, favorable safety profile and efficacy in protecting dopaminergic neurons in models of Parkinson’s disease when given by injections. The compound has the potential to slow down the progression of Parkinson’s disease and to repair some of the damaged brain tissue.

Hypothesis:
Oral formulation of small molecule compounds that activate the tissue-protective EPO receptor will demonstrate significant oral bioavailability and potential as candidate therapeutics for Parkinson’s disease. Additional formulation development will further enhance oral bioavailability improving the efficacy of the treatment.

Study Design:
The goal of this research program is to advance the lead compound in pre-clinical studies and to develop oral formulations for further development. We will develop several oral formulations of the lead compound, characterize them, and then evaluate the pharmacokinetic properties of the most promising formulations. The studies will be partly performed in collaboration with contract research organizations with expertise in formulation and pharmacokinetic studies. 

Impact on Diagnosis/Treatment of Parkinson’s Disease:             
Neuroprotective small molecule agonists of the tissue-protective EPO receptor are expected to protect against the ongoing loss of dopaminergic neurons in Parkinson’s disease. Based on prior reports on EPO receptor biology, the compounds may also support the treatment of depression and cognitive dysfunction that associate with Parkinson’s disease. 

Next Steps for Development:
Following the completion of the studies described here, the lead compound will be tested in additional pre-clinical studies using oral administration. The overall goal is to advance the lead compound into clinical trials in patients with Parkinson’s disease.