Joanna Cosgrove05.24.10
Researchers at 55 medical centers across the country have begun recruiting patients for a ground-breaking phase III clinical trial pitting coenzyme Q10 (CoQ10) against Parkinson’s disease—a coup for this incurable degenerative disorder of the central nervous system that claims 50-60,000 new diagnoses each year.
The study, helmed by Dr. M. Flint Beal, Anne Parrish Titzell professor of neurology and neuroscience at Cornell University’s Weill Medical College and New York Presbyterian Hospital, built upon years of interest in CoQ10’s ability to block cell death in the central nervous system. “It had been reported to have efficacy in patients who with known mitochondrial disorders and we suspect that mitochondrial defects occur in Parkinson’s disease, so we tested it in what’s known as the MPTP toxin model of Parkinson’s disease and we showed that it was protective,” Dr. Beal explained.
Parkinson’s disease is linked to a deficiency of dopamine in the nigrostriatal system of the brain and is typically treated with dopamine replacement therapy or dopamine agonists (drugs that stimulate the receptors involved in the action of dopamine).CoQ10’s biochemical reactions produce energy in cells and levels of CoQ10 are reported to be low in patients with Parkinson’s disease.
In a previous phase II clinical trial, the researchers concluded that higher dosages of CoQ10 were not only safe and well-tolerated in individuals with early, untreated Parkinson’s disease, they also suggested that CoQ10 had the ability to slow the progressive impairment of Parkinson’s disease as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS). Patients receiving the highest dose of CoQ10 (1200 mg/day) did not experience increased disability development, versus those who were dosed with the placebo.
The current Phase III iteration of the study, widely referred to as QEIII, endeavors to confirm and extend the results of the Phase II study, while evaluating the patient’s independent function, cognition and quality of life. “The present trial is treating with either 1200 mg or 2400 mg per day [versus a placebo] and it’s a treatment for 16 months,” confirmed Dr. Beal. “The patients are evaluated using the Unified Parkinson’s Disease Ratings Scale. They’re treated either until the end of the trial or until they have to go on dopaminergic replacement therapy.”
As for the duration of the trial, Dr. Beal said that enrollment is expected to be complete by November of this year, with the last cohort of patients due 16 months later. “We’re expecting it to end in early 2012; database and analysis to be completed by summer of 2012,” he said.
“We certainly hope it will work because it will be a breakthrough,” he exclaimed. “It will tell us that mitochondrial impairment is critical in disease pathogenesis. Both of those would be extraordinarily important.”
Because this trial has now entered Phase III, a successful result would yield an FDA approval. “I suspect what we will do in the future is try it in combination with other agents to see if we can get even better efficacy, assuming we don’t have a complete cure, which I think is highly unlikely,” he said.
Preceding research co-authored by Dr. Beal and published in the Journal of Neurochemistry (June 2009) focused on the combination therapy of CoQ10 and creatine and their ability to “exert additive neuroprotective effects in a MPTP mouse model of Parkinson's disease, a 3-NP rat model of Huntington's disease (HD) and the R6/2 transgenic mouse model of HD.”
CoQ10 and creatine are promising agents for neuroprotection in neurodegenerative diseases, the researcher wrote, because of their effects on improving mitochondrial function and cellular bioenergetics and their properties as antioxidants.
According to the study, the combination of the two agents “produced additive neuroprotective effects against dopamine depletion in the striatum and loss of tyrosine hydroxylase neurons in the substantia nigra pars compacta (SNpc) following chronic subcutaneous administration of MPTP.”
In addition, the combination of CoQ10 and creatine “produced additive neuroprotective effects on improving motor performance and extending survival in the transgenic R6/2 HD mice,” delivering the conclusion that a combination therapy of CoQ10 and creatine could be useful in the treatment of neurodegenerative diseases such as Parkinson’s disease and Huntington’s disease.