The best magazine
A Randomized, Placebo-Controlled Trial of Latrepirdine in Huntington Disease
Kieburtz K, McDermott MP, Voss TS, et al
Arch Neurol. 2010;67:154-160
Summary
The pathophysiology of Huntington disease (HD) may involve abnormal mitochondrial depolarization, causing collapse of the mitochondrial membrane and resulting in neuronal death.
Latrepirdine, a synthetic molecule that stabilizes the mitochondrial membrane, has been shown to increase neurite outgrowth in cultured neurons. The goal of this double-blind, randomized, placebo-controlled trial was to assess the safety and tolerability of latrepirdine in HD as well as its effects on cognitive, behavioral, and motor symptoms.
From July 18, 2007 through July 16, 2008, 91 participants with mild-to-moderate HD enrolled at 17 US and UK centers were randomly assigned to receive either latrepirdine 20 mg 3 times daily (n = 46) or matching placebo (n = 45) for 90 days. The main study endpoint of tolerability, which was defined as the ability to complete study treatment at the assigned dosage, occurred in 87% of patients in the latrepirdine group and in 82% of patients in the placebo group. In addition, rates of adverse events were similar in both groups (70% and 80%, respectively). Headache and somnolence were seen more often in those taking latrepirdine than in those taking placebo
Mean Mini-Mental State Examination (MMSE) score improved from baseline to day 90 in the latrepirdine group but remained stable in the placebo group (treatment effect, 0.97 points; 95% confidence interval, 0.10-1.85; P = .03). However, there were no significant treatment effects noted on the Unified Huntington's Disease Rating Scale (UHDRS) or the Alzheimer Disease Assessment Scale - cognitive subscale (ADAS-cog).
Limitations of this study include relatively small sample size, limited duration of treatment, and study not designed to detect a minimally clinically significant effect on any of the efficacy measures. Nonetheless, results from this controlled trial suggest that in the short term, latrepirdine is well tolerated in patients with HD and may have some beneficial effect on cognition, warranting further study.
Because the mechanism of action of latrepirdine differs from that of cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists, which are currently approved to treat neurodegenerative cognitive disorders (but not cognitive impairment in HD per se), latrepirdine might ultimately prove to be useful as an adjunctive treatment or in patients refractory to these other classes of drugs. Further testing of efficacy as well as of tolerability is needed.
Source: ...