NEW YORK (Reuters Health) – Patients with Huntington’s disease treated with the investigational drug latrepirdine (dimebon) showed signs of improved cognitive function in a 3-month trial, investigators report.

Huntington’s disease is thought to be caused by neuronal mitochondrial dysfunction — and latrepirdine stabilizes mitochondrial membranes, lead author Dr. Tiffini S. Voss, from the University of Virginia, Charlottesville, and her coauthors note.

The researchers add that “given the mechanism of action of latrepirdine and the lack of approved therapies for cognitive impairment in Huntington’s disease,” they undertook a tolerability trial in patients with mild to moderate disease. All of the subjects could walk on their own, and none required skilled nursing care.

At 17 centers in the U.S. and the U.K., Dr. Voss and her colleagues randomized 46 patients to receive latrepirdine (20 mg 3 times a day) and 44 to receive placebo. The 90-day treatment phase was followed by a 14-day safety observation period.

In the February Archives of Neurology, the investigators report that latrepirdine was at least as tolerable as placebo. Eighty-seven percent of the treatment group and 82% of the control group completed 90 days of treatment, with no difference between the groups in rates of adverse events or serious adverse events. Latrepirdine was, however, associated with higher rates of headache and somnolence.

The researchers also found that Mini-Mental State examination (MMSE) scores were significantly better at 90 days with latrepirdine but not with placebo (+0.86 vs -0.12 points, respectively, p = 0.03). In an analysis confined to the 51 subjects with greater cognitive impairment at baseline (MMSE score 26 or less), the improvement with latrepirdine was even more marked (+1.9 vs -0.27, p = 0.008).

This MMSE effect is comparable to results from a latrepirdine trial in Alzheimer’s disease patients, according to the authors. In that study, patients took latrepirdine for 12 months, and continued to improve over the course of treatment.

On the other hand, latrepirdine did not significantly improve patients’ scores on Unified Huntington’s Disease Rating Scale subscales for motor or functional outcomes, although there was a trend toward improved behavioral symptoms.

This trial was sponsored by Medivation Inc. (San Francisco), co-developer with Pfizer of latrepirdine. The two companies expect to release data from a second major trial of latrepirdine in Alzheimer’s patients in the first half of 2010. In addition, further studies of latrepirdine for Huntingdon’s disease are being planned.

Reference:

Arch Neurol 2010;67:154-160.