TORONTO - A huge international study that has bolstered the genetic evidence that MS has its roots in an aberrant immune system has added to questions about the validity of a theory that obstructed neck veins are behind the progressive neurological disorder.
It also raises questions about whether Ottawa and some provinces will follow through on plans to conduct patient trials of the so-called Zamboni procedure that unblocks those veins in a bid to alleviate symptoms and possibly halt progression of the disease.
The genetics study, published in this week's issue of the journal Nature, identified 29 new genetic variants common in people with multiple sclerosis, compared to those without the disease, and confirmed 23 others previously linked to MS.
Many of those genes are critical to how the immune system functions, and some of them have also been implicated in other auto-immune disorders, including Crohn's disease, Type 1 diabetes and rheumatoid arthritis.
The findings are sure to add to the controversy over the theory by Italian vascular specialist Dr. Paolo Zamboni that narrowed neck veins — which he's dubbed chronic cerebrospinal venous insufficiency, or CCSVI — are a likely cause of MS. It's estimated that thousands of Canadian patients have flocked to clinics outside Canada, paying thousands of dollars for the procedure — known as venous balloon angioplasty — to open up their veins.
Dr. John Rioux of the University of Montreal, a member of the international consortium that conducted the study, said the research was aimed at locating genetic factors underlying MS, not to look at whether or not the Zamboni procedure works.
That question can only be answered by well-designed clinical trials, he said.
Rioux, who specializes in the genetics of inflammatory diseases, said he doesn't believe there's any strong evidence suggesting that blockages in neck veins are related to an immune response.
"So I think the clearest answer you can give is there's a preponderance role to play of the immune system, and although it doesn't directly ask the question related to venous blockage, it makes it less likely," Rioux said Thursday from Montreal.
"I don't think they (the findings) bear directly. Indirectly they suggest that the immune system is the key player here."
Multiple sclerosis is an often disabling disease, which occurs when the protective coating around nerve cells, called myelin, is attacked and progressively destroyed. With an estimated 55,000 to 75,000 Canadians affected, Canada has one of the highest rates of MS in the world.
Dr. Jock Murray, a neurologist at Dalhousie University in Halifax who works with MS patients, said it's long been known that there is a genetic predisposition underlying the onset of multiple sclerosis.
"We know it's an immunological disease. You can measure the immunological phenomenon that occurs," he said, adding that the new study just adds more information about the genetic abnormalities and how they may affect the immune system.
"I think that this strengthens the knowledge we have about the genetic predisposition to the disease and the immunological basis of the disease to address those who think that this is a vascular disease as proposed by Dr. Zamboni," Murray said.
The MS Society of Canada said it welcomes the many studies examining MS, including the relationship between the disorder and genetics and CCSVI.
"Because MS is a complex disease, studying it from multiple pathways may lead to more management choices in the future," a society spokesperson said by email. "We await the results from our own funded studies on CCSVI and MS. We honour and respect the decisions Canadians living with MS make for the benefit of their own health. We acknowledge people with MS who experienced benefits from CCSVI-related procedures."
As for Ottawa and some provinces who have earmarked millions of dollars to test Zamboni's theory in future patient trials, the study's findings appear not to have diverted those plans.
In late June, federal Health Minister Leona Aglukkaq announced that despite a number of studies that cast doubt on narrowed neck veins as the primary cause of MS, an expert scientific working group that advises the government has agreed that a preliminary clinical trial should proceed.
A spokeswoman for the Canadian Institutes of Health Research said Thursday that panel of experts would be reviewing the Nature study, "one of many sources of evidence the working group will review in its ongoing efforts to analyze and monitor research on MS both here in Canada and internationally.
"The working group is continuing its work to develop the terms of reference for a phase I/II interventional trial on CCSVI and MS," Veronique Perron said by email.
Saskatchewan Health Minister Don McMorris was not available for an interview, but spokeswoman Kathy Young said the province, the first in Canada to dedicate funding to test the Zamboni procedure, "remains committed to clinical trials."
Alberta Health Minister Gene Zwozdesky said his province is also staying the course, beginning with an observational study of patients who plan to have or have already undergone the procedure.
"We've decided to go ahead with an observational study first and that would set the stage for the possibility of a clinical trial down the line if and when safety approval and ethics approval have been given," he said from Edmonton.
"But this is a somewhat controversial treatment right now ... So an abundance of caution is still required and that's why we're taking the proper time to do it the proper way," Zwozdesky said.
The province has earmarked up to $7 million for the clinical trials once it is deemed to be safe.
"Now that doesn't mean that we're not interested in learning other information," he said of the genetics study.
© The Canadian Press, 2011