alexa Prospects for Minocycline Neuroprotection
Pharmaceutical Sciences

Pharmaceutical Sciences

Pharmaceutical Regulatory Affairs: Open Access

Author(s): Plane JM

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The lack of robust treatment options available for neurodegenerative diseases, stroke, and central nervous system (CNS) trauma, all of which often involve both inflammation and apoptotic cell death, has led to an explosion of studies to reexamine the potential of established drugs for treatment of these conditions. Minocycline is a second-generation tetracycline derivative with a proven, safe clinical track record as an antibiotic and anti-inflammatory drug for treating acne and arthritis. Minocycline effectively crosses the blood-brain barrier and has demonstrated neuroprotective qualities in experimental models of CNS trauma, stroke, spinal cord injury, and neurodegenerative diseases including amyotrophic lateral sclerosis, Huntington disease, Parkinson disease, and multiple sclerosis. Thus, it is not surprising that several off-label minocycline clinical trials are under way for a variety of CNS diseases. The emerging success of some of these trials raises optimism that minocycline treatment may soon be translated into clinical practice for CNS diseases, whereas others (eg, in amyotrophic lateral sclerosis) have raised red flags. A thorough understanding of minocycline's modes of action and the targeted cellular mechanisms is warranted, as are guidelines on safe and effective doses, routes of administration, and establishment of a therapeutic window. Although several lines of evidence point to a convergent action of minocycline in suppression of both apoptosis and CNS inflammation by preventing neural cell death and by inhibiting microglial activation, the exact molecular targets of minocycline have yet to be identified and characterized. This review provides an overview of the established mechanisms of action by which minocycline exerts its neuroprotective effects, summarizes results of animal studies in experimental models of neurological diseases, and discusses results of clinical trials.

This article was published in Arch Neurol and referenced in Pharmaceutical Regulatory Affairs: Open Access

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