Groundbreaking research spurs new treatment for multiple sclerosis

V. Wee Yong, PhD hunched over the keyboard in his Heritage Medical Research Building office, typing with two fingers. The neuroscientist had the coffee pot going, as usual. Snow was already flying on the Trans-Canada Highway that his office overlooked, as a blustery mid-January day in 1998 took shape in Calgary.

He reentered the search term “matrix metalloproteinase,” which blinked back at him before fetching more information. For most people, the phrase about a family of proteins meant nothing. Nineteen years later, for people around the world with a particular type of Multiple Sclerosis (MS), Yong’s quest would mean everything.

The research that the Cumming School of Medicine’s Hotchkiss Brain Institute (HBI) professor unraveled over years of sleuth work and testing with his colleague, HBI member and Alberta Health Services neurologist Dr. Luanne Metz, has led to a cheaper and user-friendlier alternative drug to control symptoms in the early stages of relapsing-remitting MS.

They found that a common acne medication, minocycline, could safely slow the evolution from suspected MS to confirmed MS in people who have recently had their first symptoms.

It was a lengthy race to determine how the research could best help patients. Once 

Yong completed his work, the baton went to Dr. Metz.  She took the project and over a decade led three clinical trials on minocycline, with the final recently completed phase

III trial involving 12 MS centres in Canada.

“We brought our expertise to move this drug through all the phases of clinical trials,” said Dr. Metz. “We continued to find new sources of funding and we didn’t give up.”

This discovery could impact thousands of newly diagnosed MS patients each year. It’s a Calgary and Canadian success story, a“bench to bedside” process reaching from the university laboratory through clinical trials and now into the broader community, positively impacting health and quality of life.

Safe and affordable treatment option

It’s not a cure for MS, cautions Dr. Metz. There isn’t one. Yet it can reduce inflammation that causes nerve damage and provide peace of mind for many people who can now safely take a pill with a well known safety record to reduce their MS risk. They can start right away without the delay required to get special insurance approvals for other costly therapies.

“This drug like all therapies has possible side effects and should not be used without a proper indication,” said Dr. Metz. “It is not for people that worry about getting MS but have not had symptoms and typical changes on MRI.”

In Canada alone, the cost of therapies for relapsing-remitting MS falls in the range of $20,000 to $40,000 per year. For people experiencing a first clinical attack and then using minocycline, the cost drops to around $600 a year. In the United States, MS treatment often costs about three times as much as in Canada.

“It will likely be particularly important in parts of the world where some of these MS medications are not even available, as far away as India. We hope this finding is going to improve the lives of many people with MS.” said Dr. Yong.

The researchers received funding from the MS Society of Canada for the current study and previously from the Canadian Institutes of Health Research.

Top medical journal publishes study

The phase III, double-blinded, randomized, placebo-controlled clinical study – the gold standard in medicine --  was published in the New England Journal of Medicine .

Prescribing physicians who will consider minocycline for their patients can now have confidence there has been very careful peer review, said Dr. Metz.

“It’s exceedingly important that this study is being published in one of the best medical journals in the world,” she said. “It adds to the credibility of the science and the information will be spread widely. And it shows our community and the broader community that we have forward-thinking people who are leading the field.”

Long road from early research to clinical trials

When Yong first started searching for information on matrix metalloproteinase in 1998, he was working on a target. He was probing if minocycline – a tetracycline antibiotic – might be used to block the migration of immune cells into the brain and spinal cord.

“That migration of immune cells produces the plaques in MS and is responsible for many MS lesions,” explained Yong. “The more I looked, I could see that minocycline was inexpensive, it was being taken orally and safely, it was well tolerated and it had low frequency of antibiotic resistance.”

Moving step by step, the researchers worked up to applying minocycline to animal models of MS before progressing to clinical trials in 2001.

“Research has a profound impact on brain and mental health care.  Drs. Yong and Metz have provided a remarkable example of how new brain health knowledge can be generated when the laboratory is bridged to the clinic”, says HBI Director Samuel Weiss, PhD.  “This is a spectacular outcome that will positively impact people’s lives worldwide – and is a testament to the power of research excellence at the HBI and Cumming School of Medicine.”

For patients taking a pill instead of injections is a relief

Jill, 34, experienced her first sign that she could be developing MS at 27. She woke up with tingling in her hand, the numbness spread to 50 per cent of her body before she received confirmation that lesions had formed on her brain and spine. She volunteered for the two year clinical trial and kept taking the drug after the trial ended. “Joining the trial was an easy decision and the support I received throughout the process was excellent. I believe in research. How else are we going to learn?”

Jill is now symptom free and not been diagnosed with MS. After being on the drug for six years, Jill consulted with her physician and decided to stop taking the medication. “It is an antibiotic, and I wanted to give my body a break from all medication. I may go back on minocycline at some point. It’s great to have this option.” 

These days, Yong and Dr. Metz continue to work on new therapies. Yong  continues his work in the same office as years ago, though with a larger screen to display data – all the better for being able to see the big picture when researching.