May 29, 2017
MS Scientific Research Foundation funded study finds oral antibiotic, Minocycline, reduces risk of converting to MS
Clinically isolated syndrome (CIS) is a single episode of neurological symptoms suggestive of multiple sclerosis. Individuals affected by CIS have a high chance of developing MS after CIS and it is unclear why some people develop MS and others do not. Many research studies are working hard on finding treatments that stop or reverse the progression of MS, and neurologists are more frequently treating MS earlier in the disease.
In 2008 MS neurologist Dr. Luanne Metz from the University of Calgary launched a phase III, double-blind, randomized, placebo-controlled clinical trial with funding from the Multiple Sclerosis Scientific Research Foundation (MSSRF). The candidate drug? Minocycline – an antibiotic that is commonly used to treat bacterial infections such as acne, pneumonia and respiratory tract infections. Early discovery research conducted by Dr. Metz’s colleague Dr. Wee Yong from the University of Calgary demonstrated that minocycline surprisingly had anti-inflammatory and neuroprotective properties. Also funded by the MSSRF, this early work provided a strong rationale for applying minocycline as a treatment for MS, and propelled Dr. Metz into leading a phase II clinical trial for relapsing-remitting MS.
The objective of the phase III clinical trial which was recently published New England Journal of Medicine was to see if minocycline could reduce the chance that people who displayed early signs of MS (CIS) would convert to a confirmed diagnosis of MS, according to the McDonald diagnostic criteria (2005).
The clinical trial involved 142 participants across 12 Canadian MS clinics for up to 24 months. Individuals with CIS were randomly placed into one of two groups; the first group received a dose of 100mg of minocycline twice a day, and the other group received a mock drug (placebo). Both groups were followed up to 24 months, and those who went on to develop MS were considered at the “endpoint” of the study. Brain imaging was also used to determine if there were changes in brain volume or number of new lesions in the brain- an indication of the progression from CIS to MS.
At 6 months, the unadjusted risk of conversion to MS was 61.0% in the placebo group and 33.4% in the minocycline group; a difference of 27.6%. This meant that those individuals who displayed early signs of MS and who received minocycline were at significantly lower risk of converting to MS compared to those who received the placebo. Secondary imaging measures were also more improved in the minocycline group versus placebo at 6 months. The differences between the minocycline group and the placebo group were not seen at the 24 month follow-up.
The exciting results of this clinical trial illustrate that minocycline reduces the risk of developing MS in individuals with early signs of MS. Since treating a first clinical demyelinating event as early as possible is a key step in reducing the likelihood of developing clinically definitive MS, access to an effective and low-cost treatment can be highly beneficial. In Canada, the generic form of minocycline costs approximately $1 per dose. Based on two doses a day, this works out to approximately $500-600/year. The cost of minocycline will vary depending on the manufacturer, pharmacy fees and province. This is considered to be a lot lower than the thousands required for some disease-modifying therapies for CIS. There are a number of other disease-modifying therapies that are indicated for treatment of CIS, however to date there have been no clinical trials comparing minocycline with the other treatments. Additionally, the treatment effect of minocycline over 6 months appears to be similar to the treatment effect of other therapies that are indicated for CIS. Overall, these results are encouraging and as minocycline is already available, has an established safety profile, and can serve as another option for people early in the disease.
The term “bench to bedside” is commonly used to refer to research that starts in basic biomedical sciences using cells or animals, which is then translated to therapies in the clinic. This is precisely the journey of the drug minocycline, which researchers first examined in early laboratory studies and then repurposed for MS in human clinical trials. This unique Canadian research study was designed and conducted by Canadian researchers and involved Canadian patients. The MS Society of Canada and MSSRF have been behind this work from start to end- funding the initial basic biomedical science study published by Dr. V. Wee Yong and his team in 2002 in the journal Brain, to the most recent success of Dr. Metz and her team on the phase III trial. The results of these efforts will help to mobilize more options for people living with MS, and contribute to the growing movement to treat as early in the disease as possible.
Read the Minocycline FAQ for more information about the trial and what it means for people with MS.
Metz L et al. (2017) Trial of Minocycline in Clinically Isolated Syndrome of Multiple Sclerosis. N Engl J Med. [Epub ahead of Print].