With the health risks of smoking overwhelmingly clear, it's a surprising twist to find that cigarette smoke may harbor some neuroprotective secrets after all. A recent study out of Massachusetts General Hospital, published in npj Parkinson's Disease, has drawn a link between low doses of carbon monoxide, similar to those received by smokers, and a decreased risk of developing Parkinson's disease. Tapping into this complex dichotomy, research led by Stephen Gomperts, an associate professor of neurology at Harvard Medical School, has raised eyebrows and questions about a possible therapeutic approach.
The study's spark came from the consistent observation that smokers seemed to less likely develop Parkinson's disease. Addressing this puzzle, Gomperts noted, "Because smoking has consistently been associated with a reduced risk of Parkinson’s disease, we wondered whether factors in cigarette smoke may confer neuroprotection," according to The Harvard Gazette. It was the modest levels of carbon monoxide exposure in smokers that caught the eye of researchers to potentially unravel completely some of the mechanisms behind Parkinson's. Unlike nicotine, which failed to effectively slow the disease in clinical trials, carbon monoxide has shown promise as a neural protector at low concentrations.
Delving deeper, the team at Massachusetts General Hospital used rodent models to simulate the effects of carbon monoxide at levels comparable to smokers' exposure. What they discovered opened new avenues in Parkinson's research. The treatment seemed to prevent the usual loss of dopaminergic neurons and stopped the build-up of alpha-synuclein, a protein heavily implicated in Parkinson's pathology. These groundbreaking results, according to Gomperts, suggest that "molecular pathways activated by low-dose carbon monoxide may slow the onset and limit the pathology in Parkinson’s disease," as reported by The Harvard Gazette.
Not only did the rodents benefit from the carbon monoxide treatment, but the findings were also supported by human data. Researchers found that smokers had higher levels of heme oxygenase-1—a producer of endogenous carbon monoxide—in their cerebrospinal fluid, compared to nonsmokers. Moreover, in Parkinson's patients' brain samples, heme oxygenase-1 levels were higher in neurons that were free of alpha-synuclein pathology. This correlation has set the stage for further research and spurred plans for clinical trials using low-dose carbon monoxide therapies in Parkinson's patients. Gomperts told the Harvard Gazette, "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 carbon monoxide at the low doses studied here, a clinical trial of low-dose, orally administered carbon monoxide in patients with Parkinson’s disease is planned."
While further investigation is required to safely and effectively translate this into treatment, the study provides hope in a field desperate for advances. The potential therapy, however, does come with a note of caution and ethical consideration. Gomperts’s brother serves as CEO of Hillhurst Biopharmaceuticals, the company providing the oral drug product being used in the research, and disclosure forms highlighted this relationship. Considering this, the research pushes forward with backing from the Farmer Family Foundation Parkinson’s Research Initiative, the Michael J. Fox Foundation, the National Institutes of Health, and the Challenger Foundation, in addition to Hillhurst Biopharmaceuticals Inc.'s in-kind support.
