Large Trial of Oral Antibiotic Minocycline Set to Begin in People at Risk for MS; Caution urged by investigators who found same drug to be harmful in Lou Gehrig’s disease

November 1, 2007

Exciting news of the launch of a Canada-wide clinical trial of the oral acne medicine minocycline to delay the development of MS was clouded by a published report suggesting the drug was harmful in patients with ALS, a nerve disease also known as Lou Gehrig’s disease. Although ALS impacts a different part of the central nervous system than multiple sclerosis, the investigators who did that trial caution that their results may have implications for other neurological diseases including MS.

New Trial Begins:

The MS Society of Canada announced the launch of a multicenter clinical trial of the common acne pill minocycline to determine whether it can reduce neurological disease activity in people who have had a first attack of MS symptoms and are at risk for progressing to definite MS.

The trial is based on earlier studies suggesting the drug’s anti-inflammatory properties may be beneficial, including a finding that minocycline could reduce MS disease activity, as detected by magnetic resonance imaging (MRI), by 84%. Minocycline is a relatively inexpensive pill available in generic form. In addition to its anti-inflammatory and antibiotic properties, the drug is thought to inhibit the death of nervous system cells by reducing the activity of specific enzymes.

Dr. Luanne Metz (University of Calgary) will lead the two-year, placebo-controlled trial to be conducted at 14 MS clinics across Canada. The dose proposed for the Canadian MS study, 200mg daily, is half the highest dose used in the ALS study. According to a press release from the MS Society of Canada, enrollment will begin in early 2008. For questions and answers about this trial, go to this link of the MS Society of Canada’s Web site:www.mssociety.ca/en/releases/nr_20071025_faq.htm

Investigators Urge Caution:

Results of a large-scale, placebo-controlled clinical trial of minocycline involving 412 patients with ALS over 9 months of treatment found that neurological deterioration was faster in the minocycline group than the placebo group. ALS (amyotrophic lateral sclerosis) is a quickly progressive disease that kills motor neurons, the nerve cells of the central nervous system that send brain messages to muscles. Earlier smaller studies on minocycline in ALS had suggested it was safe.

The phase III trial, results of which were published inThe Lancet Neurology(early online November 1, 2007), was conducted by Dr. Paul Gordon (Columbia University, New York) and colleagues with funding from the National Institutes of Health. In their paper, the authors caution that their results compel the need to re-examine the justification for other trials of minocycline in other neurological disorders.

Commentary:

Dr. John Richert, Executive Vice President of the National MS Society (USA) Research and Clinical Programs, stated, “We applaud the MS Society of Canada for stepping forward to fund this important study.  The idea that an inexpensive pill could be repurposed to treat MS is a very exciting prospect.”

We have been informed that Dr. Metz and colleagues are aware of the ALS results. They believe that significant differences between ALS and MS, the lower dosage to be used, the ability to monitor MS disease worsening with MRI, and other factors will minimize risks to trial participants.  However, they point out that there are risks of any untested treatment, and therefore caution against the off-label use of minocycline in MS or in suspected MS outside of the controlled setting of their clinical trial.

-- Research and Clinical Programs Department