Anti-inflammatory and Neuroprotective
In various models of neurodegenerative disease, minocycline has demonstrated neurorestorative as well as neuroprotective properties. Neurodegenerative diseases such as Huntington's disease, amyotrophic lateral sclerosis and Parkinson's disease have shown a particularly beneficial response to minocycline in research studies; an antipsychotic benefit has been found in people schizophrenia and minocycline is proposed as a possible addon therapy for some schizophrenics. Current research is examining the possible neuroprotective and anti-inflammatory effects of minocycline against progression of a group of neurodegenerative disorders including multiple sclerosis (MS), rheumatoid arthritis (RA), amyotrophic lateral sclerosis (ALS), Huntington's disease, and Parkinson's disease.
In the Journal of the American Medical Association (JAMA), Chris Zink, Janice Clements, and colleagues from Johns Hopkins University reported that minocycline may exhibit neuroprotective action against AIDS Dementia Complex by inhibiting macrophage inflammation and HIV replication in the brain and cerebrospinal fluid. Minocycline may suppress viral replication by reducing T cell activation. The neuroprotective action of minocycline may include its inhibitory effect on 5-lipoxygenase, an inflammatory enzyme associated with brain aging, and the antibiotic is being studied for use in Alzheimer's disease patients. Minocycline may also exert neuroprotective effects independent of its anti-inflammatory properties. Minocycline also has been used as a "last-ditch" treatment for toxoplasmosis in AIDS patients. Minocycline is neuroprotective in mouse models of amyotrophic lateral sclerosis (ALS) and Huntington's disease and has been recently shown to stabilize the course of Huntington's disease in humans over a 2-year period.
As an anti-inflammatory, minocycline inhibits apoptosis (cell death) via attenuation of TNF-alpha, downregulating pro-inflammatory cytokine output. This effect is mediated by a direct action of minocycline on the activated T cells and on microglia, which results in the decreased ability of T cells to contact microglia which impairs cytokine production in T cell-microglia signal transduction . Minocycline also inhibits microglial activation, through blockade of NF-kappa B nuclear translocation.
A 2007 study reported the impact of the antibiotic minocycline on clinical and magnetic resonance imaging (MRI) outcomes and serum immune molecules in 40 MS patients over 24 months of open-label minocycline treatment. Despite a moderately high pretreatment relapse rate in the patient group prior to treatment (1.3/year pre-enrollment; 1.2/year during a three-month baseline period), no relapses occurred between months 6 and 24 on minocycline. Also, despite significant MRI disease-activity pretreatment (19/40 scans had gadolinium-enhancing activity during a three-month run-in), the only patient with gadolinium-enhancing lesions on MRI at 12 and 24 months was on half-dose minocycline. Levels of interleukin-12 (IL-12), which at high levels might antagonize the proinflammatory IL-12 receptor, were elevated over 18 months of treatment, as were levels of soluble vascular cell adhesion molecule-1 (VCAM-1). The activity of matrix metalloproteinase-9 was decreased by treatment. Clinical and MRI outcomes in this study were supported by systemic immunological changes and call for further investigation of minocycline in MS.
A recent study (2007) found that patients taking 200 mg of minocycline for five days within 24 hours of an ischemic stroke showed an improvement in functional state and stroke severity over a period of three months compared with patients receiving placebo.
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