According to the results of a randomised, placebo- controlled trial published in the Archives of Neurology, treatment with the investigational drug latrepirdine may improve cognitive function in patients with Huntington's disease (HD).
HD is a hereditary neurodegenerative disorder that affects movement, behaviour, and cognition. No effective treatments are currently available to alter the course of the disease or to improve cognition; the only approved therapy (tetrabenazine) treats chorea and other motor symptoms. Abnormal mitochondrial depolarisation has been implicated in the pathophysiology of HD; latrepirdine works by stabilising mitochondrial membranes, and has been previously studied in Alzheimer’s disease.
In this study, a total of 91 patients with mild to moderate HD were randomised to double-blind treatment with latrepirdine (20mg TDS; n=46) or placebo (n=45) for 90 days. The primary outcome was tolerability (ability to complete the study at the assigned dose); various efficacy measures were evaluated as secondary endpoints. The main findings were as follows:
• The study was completed by 87% of the patients randomised to latrepirdine and 82% of the placebo group; adverse event rates were also comparable (70% and 80%, respectively)
• Latrepirdine resulted in improved mean MMSE scores compared with stable performance in the placebo group (+0.86 vs. -0.12 points, respectively, treatment effect of 0.97 points; 95% CI 0.10-1.85; P=0.03).
• There were no statistically significant differences between latrepirdine and placebo for the other secondary efficacy measures (UHDRS and ADAS-cog).
The authors comment that the study was “not designed to detect a minimally clinically significant effect on any of the efficacy measures; however, [they] were better able to detect small treatment differences on the MMSE than the UHDRS or ADAS-cog because of reduced variability in the MMSE. The MMSE results suggest that latrepirdine may benefit cognition in HD, although these effects were not consistently supported by the other cognitive assessments.”
They conclude that further investigation of latrepirdine is warranted in this population with HD.
According to a Reuters report, this trial was sponsored by Medivation Inc.,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. Further studies of latrepirdine for Huntington's disease are also being planned.