Coenzyme Q10 Well-tolerated in Patients with Huntington Disease Participating in a Multi-center Phase II Trial

Annie Killoran, MD, presented findings on the tolerability of the antioxidant Coenzyme Q₁₀ (CoQ) as a potential future therapy for people with premanifest Huntington Disease. The findings were presented as part of a poster session at the 2013 Annual Meeting of the American Neurological Association. The study’s first author, Killoran is a neurologist with West Virginia University in Morgantown, WV. The study was supported by the National Institute of Neurological Disorders and Stroke.

Huntington disease (HD) is an autosomal dominant neurodegenerative disease marked by deterioration in motor skills, cognition, and behavior. People with “premanifest” HD have been diagnosed through genetic testing but don’t yet present with symptoms that are severe enough to qualify for a clinical diagnosis.

“One of the mechanisms believed to underlie the pathogenesis of Huntington disease is oxidative damage thought to be secondary to mitochondrial dysfunction,” Killoran explained. “We know that antioxidants help with oxidative damage.”

The PREQUEL trial is a phase II double-blinded and randomized trial of CoQ in people with premanifest Huntington disease. It is the first multi-center interventional trial in premanifest HD research. The researchers sought to assess whether CoQ was safe and without major side effects in these individuals. CoQ has previously demonstrated promising results in animal models of Huntington disease.

The study included 90 adults with the Huntington CAGn expansion, 93 percent of whom completed the study. All participants had a Unified Huntington Disease Rating Score of at least 3. Participants took 600 mg, 1200 mg, or 2400 mg CoQ per day. The researchers also analyzed serum levels of CoQ.

Most adverse events were mild or moderate, usually related to GI symptoms. The percentage of adverse effects did not differ significantly between treatment groups, though there was a slight upward trend of increased events with higher dosages. Eighty-nine percent of participants completed the study on their original dose, and four of the six withdrawals were on the highest dose. Serum levels of CoQ increased similar amounts with all dosages.

Killoran explained that the researchers are looking for a good biomarker to measure changes in oxidative stress, which might help demonstrate the potential clinical effectiveness of the therapy.

This study demonstrates that CoQ was well tolerated at all three doses, though it trended toward less tolerability at the highest dose. “Now we’ve shown that this is tolerable, which is important to balance the risk to harm to patients who aren’t showing any signs of disease,” Killoran concluded.

The researchers still lack information about the clinical value of CoQ in HD. Before moving into clinical trials, the researchers await the results of the 2Care Study, which is currently evaluating the effectiveness of CoQ in patients with active disease. If this is shown to be beneficial, they hope to follow up with clinical trials in patients with premanifest HD.