Scientists have discovered 29 new genetic variations linked to multiple sclerosis, with many involving genes relevant to the immune system – a finding that they say bolsters the theory that MS is a primarily an autoimmune disease.
The new study, published Wednesday in the journal Nature, is the largest-ever study on the genetics of multiple sclerosis. More than 250 scientists collaborated on the work, and close to 10,000 MS patients were involved.
Many of the gene variations the team discovered are involved in the development of the immune system's T-cells, which are the immune cells that protect against infections. When T-cells become "confused," they trigger autoimmune diseases that mistake healthy body tissues as foreign and attack them.
The study authors say the findings reaffirm the long-held assertion that MS is primarily an autoimmune disorder and that changes in the immune system set off the disease.
"Our research settles a longstanding debate on what happens first in the complex sequence of events that leads to disability in multiple sclerosis," Dr. Alastair Compston, a University of Cambridge neurology professor who was one of the leaders of the study, said in a statement.
"It is now clear that multiple sclerosis is primarily an immunological disease. This has important implications for future treatment strategies."
The findings also cast doubt on the recent theory proposed by Italian vascular surgeon Dr. Paolo Zamboni that MS is related to blocked neck veins.
For this new study, researchers in Britain, Canada and a dozen other countries performed genome-wide scans on the DNA of 9,772 people with MS. They looked for genetic anomalies that didn't appear in the DNA of 17,376 healthy people without MS.
They discovered the MS patients had 29 genetic variations that other patients didn't have. They also confirmed 23 other genetic variations that had already been associated with MS. As well, the team identified five more associations that might be significant and that require further study.
One third of the genes identified have previously been implicated in playing a role in other autoimmune diseases such as Crohn's Disease and Type 1 diabetes, indicating that the same processes occur in more than one type of autoimmune disease.
The findings cast doubt on the theory put forward by Dr. Zamboni. He suggests that blocked neck and chest veins stop blood from draining properly from the brain -- a condition he calls CCSVI -- which leads the blood to deposit iron in the brain. It's the iron deposits that lead to the brain changes that mark MS, he contends.
To treat this, he proposes a vascular procedure to open blocked and twisted neck veins. Hundreds of Canadian patients have flown to overseas clinics for the so-called "libertion treatment," spending upwards of $20,000 or more.
They've returned with various results. Some have reported the procedure helped relieve their fatigue; others said it allowed them to walk again, while still others say it offered no relief at all.
At least two patients have died after having the procedure, though it's unclear what role it played in the deaths.
Zamboni has conducted studies that suggest that the majority of MS patients have CCSVI while few healthy patients so. But further studies have been unable to replicate his findings.
One study published this week in the Archives of Neurology found no significant difference in venous abnormalities between MS patients and healthy controls. But CCSVI proponents argue the studies were performed improperly.
The vein theory has not been embraced by many neurologists who specialize in MS. Many contend that patients have a genetic predisposition for MS and that one or more environmental factors trigger the condition.
Multiple sclerosis is marked by damage to nerve fibres in the brain and spinal cord and their protective insulation, called the myelin sheath. When the myelin is destroyed, it causes patients to struggle with everyday activities such as walking, feeling, thinking and controlling the bowel and bladder.
Even among those who believe MS is an autoimmune disease, it's been unclear what sparks the immune changes. Previous research has suggested a vitamin D deficiency might be the trigger. Populations in northern hemispheres have higher rates of MS than populations with more year-round sunlight.
In this latest genetics study, researchers did identify two genetic variations that are involved in the metabolism of vitamin D.
The MS Society of Canada said it welcomed the new study, as well as all new studies looking at the relationship between MS 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 in an email to The Canadian Press.
"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."
