After more than three decades of dead-ends and dismay for researchers and Multiple Sclerosis (MS) sufferers alike, two new genes have finally been identified that are thought to be involved in the pathogenesis of MS: the most common neurological disease affecting young adults.
Back in 1972, the first development in the link between genes and MS was made when the human leukocyte antigen (HLA) region of the genome was associated with MS. Since then, there has been a frustrating lack of new advances into the disease which affects 85,000 people in the UK alone. However, the first genome profile of MS - published this week in the New England Journal of Medicine - has implicated two more genes and confirmed the centrality of HLA family of genes in the disorder.
The two genes IL2RA andIL7RA are both interleukin receptors - part of an immune system enhancing pathway. The variant genes found in those affected by the disorder initially appear to have a reduced activity.
Multiple Sclerosis is a disorder where the body's immune system, instead of attacking pathological invaders, turns on itself and targets the fatty myelin sheaths which surround and protect neurons - so-called auto-immunity. This inappropriate assault leads invariably to neuronal dysfunction, resulting in: numbness or tingling in any part of the body, fatigue and dizziness, limb weakness, spasticity, pain and cognitive impairment.
'This discovery brings us into a whole new pathway that could have a very important role in understanding the fundamental mechanisms that trigger MS' said Stephen Hauser at the University of California in San Francisco, US, who worked on both the Nature Genetics papers.
Current thinking suggests that MS is a complex interplay of genetics, environment and lifestyle. The variants uncovered are not rare mutations as seen in single gene disorders, such as muscular dystrophy or sickle cell anaemia. Instead, they are found in the 'normal' population and, in isolation, represent only a modest risk. The lack of obviously high-risk alleles has probably led to theDNA difficulty in defining the genetic architecture of MS.
The study - part of the Multiple Sclerosis Genetics Consortium - attempted to define the genetic profile of the disorder by looking at 330,000 SNP markers, which are single letter variants in a gene's DNA code, in 931 family trios (consisting of an affected child and both parents). The work has subsequently been confirmed by two further studies published in Nature Genetics.
In some completely isolated work, monoclonal antibodies targeting IL2R are showing clinical efficacy in phase two studies.