Minocycline is an oral antibiotic used to treat acne or bacterial infections including respiratory and urinary tract infections. The therapy is currently being studied for use in people with relapsing-remitting multiple sclerosis (RRMS) or clinically isolated syndrome (CIS), referring to the first episode of neurologic symptoms that last at least 24-hours and are caused by myelin damage.
How minocycline works
The symptoms of MS are caused by the immune system mistakenly attacking and damaging the myelin sheath (a protective layer that surrounds nerve fibers), leading to disrupted nerve signaling and eventual permanent nerve damage. The damage can be caused by immune cells, such as T-cells, entering the brain and spinal cord and triggering inflammation of nerve tissue.
Minocycline is believed to have immunomodulatory (altering the immune system), anti-inflammatory, and neuroprotective properties, which makes the antibiotic an interesting potential candidate for the treatment of MS. Minocycline can influence T-cells in several ways. For example, it can reduce inflammation by preventing T-cells from producing cytokines, proteins that can trigger the inflammatory response. It can also reduce the number of T-cells available that damage nerves by preventing T-cell proliferation. Finally, it can prevent T-cells from crossing the blood-brain barrier (BBB) and access the brain and spinal cord.
Minocycline in clinical trials
Minocycline has been tested alone and in combination with other drugs in clinical trials for both RRMS and CIS.
Teva Pharmaceuticals sponsored a Phase 2 trial (NCT00203112) to assess whether minocycline could improve the efficiency of their MS drug, Copaxone (glatiramer acetate), in patients with RRMS. The multicenter, double-blind, placebo-controlled trial tested the combination (compared to a Copaxone-placebo combination) in 44 patients over nine months. The results, published in the scientific journal Multiple Sclerosis, were promising as the treatment was well tolerated and a significant reduction in the number of new lesions was observed in the treatment group compared to the placebo.
A Phase 2 multicenter, double-blind, placebo-controlled trial (NCT01134627) was carried out by Merck to determine the effect of minocycline in combination with Rebif (interferon beta-1a) in RRMS patients. However, this trial was terminated in 2013, as it showed no statistically significant benefits.
A Phase 3 double-blind placebo controlled Canadian study (NCT00666887) of minocycline in people with CIS was completed in 2015. Results showed that doses of 100 mg of oral minocycline twice daily for six months reduced the relative and absolute risk of MS in people who experienced CIS by 44.6% and 27.4%, respectively. The results are published in the The New England Journal of Medicine.
The most common side effects of minocycline are diarrhea, dizziness or light-headedness, skin and gum discolorations, sun sensitivity, and fungal infections.
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