Tag Archives: Collaborative Grant

Emerging therapies at AAN – the B cell movement

Neurologist and leading MS researcher Dr. Amit Bar-Or from the Montreal Neurological Institute at McGill University presented data on an emerging MS treatment called ofatumumab at the American Academy of Neurology Annual Meeting last week. Ofatumumab is a monoclonal antibody targeted against a protein commonly found on B cells called CD20. It is currently indicated for the treatment of chronic lymphocytic leukemia, but has been recently identified as a potential treatment of autoimmune diseases such as MS.

Dr. Bar-Or presented results from a phase II clinical trial looking at the safety, efficacy and dose response of ofatumumab in people with relapsing-remitting MS.

The study recruited 231 participants who were randomly assigned to one of 5 treatment groups: 3mg every 3 months, 30mg every 3 months, 60mg every 3 months, 60mg every month, and placebo (mock treatment). Participants were given ofatumumab via under-the-skin injections over a period of 6 months and also took part in follow-up studies. The efficacy – ability to produce a beneficial effect – of ofatumumab was determined by its ability to reduce lesions as observed on MRI.

At 12 weeks, treatment with ofatumumab resulted in a significant reduction in the number lesions compared to placebo. The reduction in lesions was observed for all doses. Researchers also reported a linear relationship between suppression of B cell activity and residual disease activity, with 1 new lesion per year with treatment versus 16 new lesions per year without treatment. The drug showed a good safety profile, with reports of some adverse events including injection-site reactions. There were no serious infections, PML cases or immunogenicity (immune reactions against the drug) observed.

Ofatumumab, which is currently being developed by pharmaceutical company GlaxoSmithKline, adds to the growing list of MS therapies in the pipeline. It is also one of two emerging MS therapies targeting B cells, the other being ocrelizumab. Like ofatumumab, ocrelizumab targets the CD20 protein and is currently in phase III trials led by scientists at Roche.

B cells have gained increasing interest among the MS research community over the years. When trials involving B-cell targeted treatments showed marked improvements in people with MS, researchers acknowledged that B cells are important players in MS disease. Last year, the MS Society and MS Scientific Research Foundation launched a $3.6 million dollar collaborative, multi-site study led by Dr. Bar-Or which seeks to understand how different types of B-cells impact the development and progression of MS, how they may have a role in progressive MS, and how they can be therapeutically targeted to improve health without harming other parts of the immune system. I had a chance to chat with Dr. Bar-Or after his presentation at the conference to get a more in-depth look at ofatumumab and B cells.

Here is what he shared with me.

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What comes first, the chicken or the egg? Science points to another perspective on how MS begins

At almost every MS research conference I’ve attended, one of the most actively discussed topics is immunology. It is clear that that the immune system is acting in an uncharacteristic way in MS, as evidenced by many elegant experiments showing a build-up of immune cells in the brain and spinal cord causing severe tissue damage. These studies encourage the belief that MS begins with the immune system.

But there are a group of scientists that are now wondering whether, in MS, the immune system misbehaves causing tissue damage, or if the break down of nerve tissue is actually taking place before the immune cells arrive and cause more harm.

This important example of ‘which came first, the chicken or the egg?’ has prompted new research that is moving away from the immune system and focusing efforts on trying to understand the mechanism of tissue breakdown in the nervous system, also known as ‘neurodegeneration’.

In 2011, the MS Society funded an extensive, multi centre research grant spearheaded by Dr. Peter Stys from the University of Calgary. Dr. Stys is interested in learning more about neurodegeneration and whether this is the first step in propagating MS. He presented data here at the endMS conference which challenges the conventional wisdom that MS is an autoimmune disease driven by white blood cells that enter the nervous system and break down tissue. Instead he proposes that perhaps the tissue is undergoing some process of degeneration first, followed by inflammation through mechanisms that may involve copper or other key molecules.

Research in this area is critical as it would not only provide clues about the cause of MS, but also insights on progressive MS which is characterized more so by tissue damage rather than inflammation.

This alternative view of the cause of MS was supported by data presented by MS Society funded researcher Dr. George Harauz from the University of Guelph. In his presentation Dr. Harauz provided very detailed descriptions of the structure and function of myelin – one of the most important substances in the brain and also a major target of harmful immune cells in MS. Dr. Harauz stated that it is possible that early alterations to myelin may, down the road, lead to development of MS. I had a chance to chat with Dr. Harauz, who has been studying myelin and MS at the University of Guelph for over 25 years.

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