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Comment & Response
May 18, 2020

Minocycline—A Lesson From a Failure

Author Affiliations
  • 1Center for Advanced Studies and Technology, University G. d’Annunzio of Chieti-Pescara, Chieti, Italy
JAMA Neurol. 2020;77(8):1037-1038. doi:10.1001/jamaneurol.2020.1154

To the Editor The development of novel and effective strategies aimed at modifying the course of Alzheimer disease (AD) is urgently needed. In a recent double-blind randomized clinical trial, Howard and colleagues1 reported that minocycline, a broad-spectrum antibiotic, failed to provide clinical benefits (as assessed by changes in scores of the Mini-Mental State Examination and the Bristol Activities of Daily Living scale) in a cohort of persons with a diagnosis of early AD. The rationale for the investigation of minocycline stems from preclinical evidence supporting the notion that the drug targets critical determinants of AD-like β-amyloid, hyperphosphorylated tau, and microglia activation and neuroinflammation.

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1 Comment for this article
Minocycline and Neurological Therapeutic Trials
Khichar Shubhakaran, MD (Med), D.M.(Neurology) | Senior Professor and Head of Department of Neurology, MDM Hospital, Dr. S. N. Medical Colleg, Jodhpur, India-342003
Although the major indication for minocycline is acne treatment, its neuroprotective and immunomodulatory roles are of significant interest as shown in various studies (1-4). Minocycline is a broad spectrum antibiotic, and has been studied in various neurological therapeutic trials like a neuroprotective agent in stroke, where it was found to be of no use in a smaller trial (1) but showed better outcomes in a larger trial (2). In a Canadian trial presented at the European Committee for Treatment and Research in Multiple Sclerosis 2015 Congress, after 6 months of minocycline treatment, there was reduction of absolute risk of developing multiple sclerosis (MS) by 27.4% with a relative risk of 44.6% compared with placebo (3), comparable with other approved therapies. Besides the specialty of neurology, minocycline is recognized as a disease-modifying anti-rheumatic drug by the American College of Rheumatology (4). Now it is being tried in Alzheimer Disease (AD) where there the issue of doubt in efficacy is raised (5). Of course minocycline is not without side effects like potential vasculitis (6).  So we have to see more in further trials so as to overcome the various issues relating to minocycline use.

1. Kohler E, Prentice DA, Bates TR, et al. Intravenous minocycline in acute stroke: a randomized, controlled pilot study and meta-analysis. Stroke 2013;44:2493-2499.
2. Padma Srivastava MV, Bhasin A, Bhatia R, et al. Efficacy of minocycline in acute stroke: a single-blinded, placebo-controlled trial. Neurol India 2012;60:23-28.
3. Metz LM, Li D, Traboulsee A, et al. Minocycline reduces the relative risk of multiple sclerosis in people experiencing their first clinical demyelinating event by 44.6%: results of a phase III double-blind placebo controlled Canadian multicentre clinical trial. ECTRIMS Online Library 2015;116700.
4. Chang C, Gershwin ME. Drugs and autoimmunity--a contemporary review and mechanistic approach. J Autoimmun 2010;34:J266-J275.
5. Howard R, Zubko O, Bradley R, et al; Minocycline in Alzheimer Disease Efficacy (MADE) Trialist Group. Minocycline at 2 different dosages vs placebo for patients with mild Alzheimer disease: a randomized clinical trial. JAMA Neurol. 2019;77(2):164-174. doi:10.1001/jamaneurol.2019.3762
6. Baratta JM, Dyck PJB, Brand P, et al. Vasculitic neuropathy following exposure to minocycline. Neurol Neuroimmunol Neuroinflamm 2016;3:e180.