In MS, the immune system attacks myelin, the fatty sheath that protects the cells of the central nervous system. As a result, nerve signals get slowed or blocked, causing difficulties in movement and coordination, muscle weakness, cognitive impairment, slurred speech and vision problems. There is no known cure.
Scientists have known for three decades that the disease has a genetic cause, but the mechanism has remained obscure. The new find - the product of eight years' work - is a variant of a gene known as KIF1B.
Gene variant traced to common ancestor
Trolling through municipal and church records, a team led by Rogier Hintzen of the Erasmus Medical Centre in Rotterdam found 26 MS patients in southern Holland who - unbeknownst to them - all had a common ancestor dating back to the early 18th century.
The researchers then scanned each individual's genomes to see if they shared any genetic anomalies.
"We found a peak in the KIF1B gene, which was very exciting because its function is well known and fits so well," said Hintzen.
The handful of genes previously known to be implicated in the debilitating disease all help shape the defence mechanism our bodies use to ward off infection. But KIF1B plays a critical role in the transport of signals along metre-long neurons between the brain and the spinal cord, said Hintzen. Their length makes them particularly vulnerable to damage or attack.
After gaining this nugget of knowledge, Hintzen then cast the same genome-wide net among 2 597 individuals with MS from the Netherlands, Sweden and Canada, and compared the data to an even larger control group.
The results showed a slightly higher risk of MS when the suspect gene variant was present.
Unknown pathway discovered
"But what makes this find spectacular is that it points to a pathway that was unknown, and that must be involved in the pathological process," Hintzen said. "It makes perfect sense, because this gene is a kind of motor for transport in neurons."
Many MS patients are in a wheelchair within a year or two of the onset of the disease. In 10% of cases, though, MS remains strangely benign after an initial episode.
The study, published in the journal Nature Genetics, suggests that the suspect variant may account for the divergent outcomes. "It is probably the way the nerve tissue deals with the attack that makes the difference," said Hintzen. If so, the variant could become a target for drug therapies, he said.
The next step is to design clinical trials that will test the presence of the variant in both sub-groups of MS sufferers – those with the one-off episode of the disease and those with the degenerative form.
With luck, this will confirm the precise mechanism that removes the shield protecting the nervous system. – (Marlowe Hood/Sapa)