Key findings

• Treatment with an oral formulation of CO at low dose comparable to that experienced by smokers protected against hallmark features of PD in animal models, including loss of dopamine cells and accumulation of α-synuclein pathology.
• Low dose CO activated signaling cascades that limit oxidative stress and degrade α-synuclein, the protein that aggregates in neurons in PD.  
• Heme oxygenase 1 (HO-1), a key protein in the oxidative stress response that was increased with CO exposure, was higher in the cerebrospinal fluid (CSF) of human smokers compared to nonsmokers. In PD brain samples, HO-1 levels were higher in neurons free from α-synuclein pathology.

Why is this important?

• These findings suggest that molecular pathways activated by low dose CO may slow onset and limit pathology in PD. 
• They support further investigation into low-dose CO and the pathways it modifies to slow disease progression in PD.
• These observations suggest that CO may contribute to the reduced risk of PD among smokers.

What's next?

• The research team is studying the pathways activated by low dose CO in experimental models to determine how they provide neuroprotection and to optimize their efficacy. 
• Building on multiple Phase 1 and Phase 2 clinical studies in both healthy people and people with a variety of clinical conditions showing safety of CO at the low doses studied here, a clinical trial of low-dose, orally administered CO in PD patients is planned.