Minocycline Safety and Tolerability in Huntington's Disease
Presenter:
Merit Cudkowicz, Massachusetts General Hospital, Boston, Massachusetts USA
Background:
Minocycline is a semisynthetic second generation tetracycline that in addition to its antimicrobial action, inhibits release of cytochrome c from the mitochondria and the subsequent caspase 1 and 3 activation and microglial reaction. Caspase activation has been implicated as a possible pathophysiologic mechanism in Huntington’s disease (HD). Minocycline prolongs survival by 14% in a transgenic mouse model of HD.
Methods:
A double-blind, randomized, placebo-controlled study of minocycline in 60 patients with HD was conducted at 8 centers. The primary outcome measure was the tolerability of minocycline (100 mg/day and 200 mg/day) compared with placebo over 8 weeks of treatment. Secondary endpoints included additional safety measures and the change in Unified Huntington’s Disease Rating Scale (UHDRS) subscores.
Results:
There were no differences among the three groups in baseline variables or UHDRS scores. Fifty-four (90%) subjects completed the study. Tolerability was similar between treatment groups and placebo (One-sided Z test, p = 0.10 and 0.28). There were no differences in the frequency of adverse events or vital signs among the study groups. At week 8, the mean platelet count dropped slightly with minocycline treatment (36.5 x109/L at 100 mg/day and 45.00 x109/L at 200 mg/day, p = 0.02, trend test). Minocycline treatment had no effect on UHDRS scores.
Conclusions:
Over 8 weeks, minocycline at 100 mg and 200 mg per day was well tolerated and safe in HD.
Supported by grants from the FDA Office of Orphan Products Development, Huntington's Disease Society of America, and Hereditary Disease Foundation.
Presented at the 17th Annual Symposia on Etiology, Pathogenesis, and Treatment of Parkinson’s Disease and Other Movement Disorders on Sunday, October 19, 2003, at the San Francisco Marriott, San Francisco, California
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