Multiple Sclerosis Society of Canada

Minocycline


Overview:

  • Route of Administration: Oral
  • Type: Tetracycline antibiotic
  • Emerging treatment for: Clinically isolated syndrome, RRMS
  • Status: Completed Phase III clinical trial

How it Works

In addition to its antibacterial activity, minocycline boasts both anti-inflammatory and neuroprotective properties that make it a promising therapeutic candidate for MS. Minocycline has been shown to suppress the activity of various pro-inflammatory cells and molecules, and prevent the infiltration of immune cells into the central nervous system.

Minocycline is hypothesized to promote neuroprotection through three mechanisms: inhibiting the death of myelin-producing cells; reducing cellular damage to nerve fibres through its antioxidant properties, and; protecting against excitotoxicity, the process by which nerve cells are damaged or destroyed by excessive stimulation by certain brain chemicals

Research and Results

A number of animal studies and human pilot trials have conferred beneficial properties of minocycline in MS. Further, a phase II, multi-centre, double-blind, placebo-controlled clinical trial led by Dr. Metz and team compared the efficacy of minocycline administered in combination with glatiramer acetate to glatiramer acetate and placebo in 44 participants with relapsing-remitting MS. Treatment with minocycline and glatiramer acetate reduced the number lesions on MRI, although it did not reach statistical significance.

In 2007 Dr. Metz received funding from the Multiple Sclerosis Scientific Research Foundation to launch a phase III clinical trial observing the safety and efficacy of minocycline in patients who experienced initial symptoms, called clinically isolated symptoms (CIS),suggestive of MS. The trial enrolled 142 participants who were randomly assigned to receive either minocycline at a dose of 100mg orally twice-a-day, or placebo. The study was carried at MS clinics in Vancouver, Burnaby, Calgary, Edmonton, Winnipeg, London, Toronto, Ottawa, Montreal, Greenfield Park, Quebec City, and Halifax.Results published on June 1, 2017 in the New England Journal of Medicine demonstrated that minocycline reduced conversion from CIS to MS by 27.6% (p=0.001) within 6 months.While 61% of placebo-treated participants reached MS within 6 months only 33.4% of minocycline-treated participants did.

Adverse Effects Reported

Minocycline has an established safety track record based on several decades as an indication for acne vulgaris. The most common short term side effects in people treated with minocycline observed in MS trials include: rash, diarrhea; dizziness or light-headedness; grey discoloration of the skin or tissue in the mouth including the teeth; sun sensitivity and secondary infection due to fungi which can cause itching of the rectum or vagina.

Supporting Materials

References

1. Metz LM, Li D, Traboulsee A, Myles ML, Duquette P, Godin J, Constantin M, Yong VW, GA/minocycline study investigators. Glatiramer acetate in combination with minocycline in patients with relapsing--remitting multiple sclerosis: results of a Canadian, multicenter, double-blind, placebo-controlled trial. Mult Scler. 2009; 15(10):1183-94.

2. Zhang Y, Metz LM, Yong VW, Bell RB, Yeung M, Patry DG and Mitchell JR. Pilot study of minocycline in relapsing-remitting multiple sclerosis. Can J Neurol Sci. 2008; 35(2):185-91.

3. Zabad RK, Metz LM, Todoruk TR, Zhang Y, Mitchell JR, Yeung M, Patry DG, Bell RB and Yong VW. The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study. Mult Scler. 2007; 13(4):517-26.

4. Metz LM, Li D, Traboulsee A, Duquette P, Eliasziw M, Cerchiaro G, Greenfield J, Riddenhough A, Yeung M, Kremenchutzky M, Vorobeychik G, Freedman M, Bhan V, Blevins G, Marriott J, Grand’Maison F, Lee L, Thibault M, Hill M, Yong VW. Trial of Minocycline in Clinically Isolated Syndrom of Multiple Sclerosis. New Eng J Med. 2017; [Epub ahead of print].