Study Rationale: Brain inflammation plays an important role in the pathology of Parkinson’s disease (PD). One of the key proteins involved in this inflammatory process is STING (stimulator of interferon genes). This inflammatory protein therefore presents an attractive target for therapeutics, and several STING inhibitors have already been discovered and validated. In this project, we will test these STING inhibitors to find those can most effectively penetrate the blood-brain barrier and that are viable candidates for potential PD therapeutics alone or in combination with existing treatments and standard-of-care.
Hypothesis: We hypothesize that brain-penetrating STING inhibitor molecules will significantly quell the neuroinflammatory components of PD.
Study Design: In the first part of our study, we will profile STING inhibitors for their ability to permeate the human blood-brain barrier permeation and and for their anti-neuroinflammatory potency and efficacy (milestone 1). Next, we will identify the STING inhibitor with the strongest brain-penetrating capabilities and test its efficacy in quelling neuroinflammation in a preclinical alpha-synuclein PD model (milestone).
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: Upon successful completion of these milestones, we will perform IND-enabling studies with a full toxicology workup and assessment of systemic and CNS metrics. In parallel, we will engage interested industry parties in an ‘option to license’ deal to help fund the final aspects of preclinical development and secure an IND.