Trial Shows Minocycline Has A Harmful Effect On Patients With Motor Neuron Disease

Minocycline is an off-the shelf anti-inflammatory and anti-apoptotic drug that is neuroprotective in animal models of stroke, trauma, and neurodegenerative disorders, and also prolongs survival and reduces motor neuron loss in transgenic mouse models of ALS. Phase II trials suggested that minocycline could be taken safely by patients with ALS. On the basis of these positive results plans were made for many trials of minocycline in neurodegenerative conditions.

Dr Paul H Gordon (Columbia University, New York, USA) and colleagues in the United States Western ALS Study Group did a randomised phase III trial to test the efficacy of minocycline as a treatment for ALS in 412 patients. Compared with patients who took placebo, minocycline-treated patients deteriorated at a 25% faster rate according to the ALS functional rating scale (ALSFRS-R), and showed non-significant tendencies towards faster decline of forced vital capacity (FVC) and muscle strength.

In light of these findings, the authors suggest that trials of minocycline in other neurological diseases should be reassessed, as minocycline might be detrimental in patients with neurological diseases other than ALS. They conclude: “Our results are contrary to many published reports from laboratories, and thus have implications for trials of minocycline in patients with other neurological conditions, for the preclinical evaluation of potential neuroprotective therapies, and for the design of future clinical trials in ALS”.

In an accompanying comment Dr Michael Swash highlights the need for early diagnosis in ALS: “Clinicians and patients alike would prefer ALS therapy to be tested as early as possible, but there are unresolved difficulties with accurate early diagnosis, particularly the absence of a specific diagnostic test. Might some of the compounds that have failed in clinical trials show benefit if tested at disease onset in human beings?” He concludes that the time has come for new approaches to trial design: “The aim must be to design informative, short, inexpensive, and sensitive phase I/II studies before large phase III studies are attempted”.