Study Rationale:
Although carbon monoxide (CO) is commonly considered harmful, a growing body of research suggests that low doses of CO can stimulate physiologic processes that may protect against brain cell loss in Parkinson’s disease (PD). Consistent with this possibility, epidemiology studies have found that cigarette smoking, which exposes smokers to CO, is associated with a lower risk of PD. Together with preliminary data showing that low-dose carbon monoxide reduces the death of dopamine-producing neurons and the accumulation of alpha-synuclein aggregates in pre-clinical models of PD, these observations suggest that low doses of CO may be neuroprotective in PD.
Hypothesis:
We hypothesize that HBI-002, a liquid formulation of CO, will provide neuroprotection in pre-clinical PD models.
Study Design:
HBI-002 will be tested rigorously in different genetic and toxin-induced pre-clinical models of PD. We will assess the dose response and identify the amount of HBI-002 that confers in maximal neuroprotection in PD models. We will dissect the cellular and molecular mechanisms underlying HBI-002-mediated neuroprotection, and we will evaluate preclinical safety of HBI-002 in the brain.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
If successful, this research will provide critical proof-of-concept for clinical development of HBI-002 to prevent the progression of PD.
Next Steps for Development:
If this study is successful, the next step in development is, upon regulatory approval, to conduct a clinical trial in people with PD to confirm the safety and assess the efficacy of this new treatment.