Study Rationale: Brain inflammation plays an important role in the pathology and progression of Parkinson’s disease (PD). One of the key proteins involved in this inflammatory process is STING (stimulator of interferon genes). With initial funding from MJFF, we identified a novel compound, INRx-H001, that inhibits the pro-inflammatory function of STING in cells and can also enter the brain when administered orally. Together, these findings suggest that INRx-H001 has therapeutic potential for attenuating the neuroinflammation associated with PD. In this project, we will identify and study compounds that show improved solubility and potency while retaining the ability to inhibit STING-associated inflammation.
Hypothesis: We hypothesize that compounds that optimize the potency and safety of INRx-H001 will show efficacy in slowing the progression of PD.
Study Design: We will optimize the solubility and potency of INRx-H001 and characterize the resulting compound’s absorption, distribution, metabolism and excretion. We will expand the compound’s target engagement, conduct pharmacodynamic and pharmacokinetic studies and examine its neuroprotective efficacy in preclinical models. We will also conduct IND-enabling toxicology studies in multiple preclinical models.
Impact on Diagnosis/Treatment of Parkinson’s Disease: The neuroinflammatory aspects of PD are an important focus of applied research and the STING inhibitors we develop could become standalone therapies for PD or could be administered in combination with existing treatments.
Next Steps for Development: In addition to performing IND-enabling toxicology studies, we will complete a full assessment of systemic and CNS metrics. We also plan to engage interested industry parties in an ‘option to license’ deal to help fund the final aspects of preclinical development and secure an IND.