Identifying the genes involved in multiple sclerosis

Scientists at Serono have made a breakthrough in understanding the genetic basis of multiple sclerosis (MS).

It has been known for some time that, despite susceptibility to multiple sclerosis running in families, it is not an inherited condition, but now researchers at Serono have managed to identify and create a register of 80 genes involved in the inflammatory and neuro-degenerative pathways of MS.

The chronic inflammatory condition of the nervous system is the most common non-traumatic neurological disease in young adults and is thought to affect as many as two million people worldwide. Although symptoms vary, the most common include blurred vision, numbness or tingling in the limbs, and problems with strength and co-ordination. There are a number of different forms, but the relapsing ones are the most common.

A large-scale association study was carried out in three populations (France, Sweden and the US), totalling 900 people with MS and a similar number of healthy individuals. Scientists at the Serono Genetics Institute at Evry, outside Paris, scanned more than 100,000 single nucleotide polymorphisms (SNPs) using Affymetrix GeneChip technology; these were compared between the patients with the disease and those without it to pinpoint the genes involved in MS. A total of 80 genes were found to be statistically significant in all three populations, including one of the seven genes previously thought to be involved in MS. 'These are the ones we are sure are involved in MS,' said Daniel Cohen, worldwide head of genetics at Serono.

The genes also provide potential new drug targets: 'for our 79 new genes, at least half of them encode for proteins which can be modulated by therapeutics,' added Cohen. The genes are involved in several different pathways, notably inflammation and neurodegeneration, as well as some novel pathways.

Thus far, a 40% scan of the genome has been carried out. The team now plans to apply the next generation of GeneChip technology to scan more than half a million SNPs, with the aim of completing the whole genome scan in 2006.

Tim Wells, Serono's senior vice president of research, claims that one of the reasons so many biotech drugs fail is that they are too far abstracted from the disease process in humans: 'we have a unique biotech approach that brings human genetics into all stages of the discovery process, increasing our success in the clinic. We are looking at real human disease.'