I believe that there are two reasons for the interest. First, although our study was a phase II study and too small to be definitive, it was the first study to provide strong evidence that a treatment can slow the progressive impairment of Parkinson disease. My colleagues and I have submitted a proposal to the NIH to conduct a definitive phase III study. Second, there is considerable interest in the role of mitochondria in neurodegenerative disorders, and the compound that we studied, coenzyme Q10, is an integral component of the electron transport chain, as well as an antioxidant. Our study provided evidence that therapies targeted at mitochondria may have a clinical effect. Also, we used a novel clinical trial design, which was developed by Dr. David Oakes of the University of Rochester and colleagues in the Parkinson Study Group. The trial design, which has been given the nickname of the "Oakes 1" design, allows studies of interventions that might slow the progression of Parkinson disease with fewer subjects and in a shorter time.

The study was the result of a research effort into the biology of Parkinson's disease that Dr. Richard Haas and I began at the University of California, San Diego (UCSD) in the early 1990s and a close collaboration with Dr. Flint Beal of Weill Medical College of Cornell University, which began about 10 years ago. The research was stimulated by the discovery by Dr. Bill Langston that a toxin, MPTP, can cause Parkinsonism in humans and the subsequent discovery that MPTP acts through inhibition of complex I of the mitochondrial electron transport chain. Dr. Tony Schapira reported a selective decrease in complex I activity in the substantia nigra (the part of the brain most affected in Parkinson disease) in brains from patients with the disease. Dr. Haas and I reasoned that if mitochondrial impairment is involved in the pathogenesis of Parkinson disease, then it should occur in patients with early disease, who are not yet on therapy for the disorder. We performed a study in which mitochondrial function was evaluated in platelets from patients with early, untreated Parkinson disease, age- and gender-matched control subjects and spouses, who served as a control for the home environment. We found a significant reduction in complex I activity in the Parkinson disease patients compared to both control groups, supporting a role for mitochondrial dysfunction in the development Parkinson disease. We noted that coenzyme Q10 is the electron acceptor for both complex I and complex II of the electron transport chain. Working with Dr. Beal we found a significant reduction (33%) in the level of coenzyme Q10 in mitochondria in the Parkinsonian patients compared with age- and gender-matched control subjects. Dr. Beal and I then demonstrated that oral treatment of one-year-old mice with coenzyme Q10 could attenuate damage to the nigrostriatal system caused by MPTP. After a pilot study of high doses of coenzyme Q10 in Parkinsonian patients, working with the Parkinson Study Group we were funded by NINDS to carry out our phase II study in patients with early, untreated Parkinson disease.

Our study demonstrated a positive trend for treatment of patients with early Parkinson disease with high doses of coenzyme Q10 to slow the progressive impairment that occurs in the disease. We have submitted a proposal to the NIH for a larger, definitive phase III trial, which hopefully will confirm and perhaps extend the results of our phase II study.