Neuroprotection in Huntingtonʼs disease: a 2-year study on minocycline

Huntingtonʼs disease (HD), a relentlessly progressive neurodegenerative disorder, is characterized by a clinical triad of psychiatric, cognitive and motor disturbances. The antibiotic minocycline, a caspase inhibitor exhibiting antiapoptotic properties, has been shown to prolong survival in the transgenic mouse model of HD. We administrated minocycline to 14 patients with genetically confirmed HD. The patients were psychiatrically, neurologically and neuropsychologically evaluated at baseline, and after 6 and 24 months of treatment, using the Unified HD Rating Scale and a neuropsychological test battery. After 12 months, three patients were lost to follow-up so that 11 patients were analysed at the endpoint. Minocycline was well tolerated. Unlike the expected natural course of HD, patients exhibited stabilization in general motor and neuropsychological function at endpoint, after improving in the first 6 months. Moreover, we found a significant amelioration of psychiatric symptoms that was not apparent after the first 6 months. In detail, the Mini-Mental State Examination, the Total Motor Score, the Total Functional Capacity Scale and the Independence Scale, as the most prominent scales in HD, were stabilized after 3 years of treatment. Our results confirm previous animal studies and indicate a neuroprotective effect of this agent in HD. A long-term, double-blind, placebo-controlled trial appears highly warranted for definitively establishing the value of minocycline in HD.