Monday, October 02, 2006

Twin genes do battle over multiple sclerosis

Press releases 2006 : 27 Sep: Genes & MS

Scientists have found that a risk gene for multiple sclerosis (MS) is fought by a twin gene which tries to dampen the effects of the disease.

The gene that puts a person a risk of MS - DR2b – is always found with its partner, DR2a. This protective twin masks the risk gene’s negative effect by redirecting the immune system to prevent it from attacking the body. Overall this fight reduces the severity of MS symptoms.

The research, published in Nature, also reveals that positive natural selection is at work, because DR2b is never passed on without the modifying gene DR2a. Positive selection means that the genes are inherited together, not by chance but because their pairing gives an advantage.

One of the lead researchers, Professor Lars Fugger, a clinical immunologist based in the Medical Research Council Human Immunology Unit explains: ‘Multiple Sclerosis is an autoimmune disease, in other words, it is caused by the immune system attacking the body. The DR2b gene clearly tells the immune system to go hard into battle against the body’s own tissue, so it starts to work in a way that actually damages the person. For this reason, natural selection has eliminated the gene on its own, but allowed it to be inherited only when it is accompanied by another gene [DR2a] which tempers its effect.’

Using mice bred to carry different combinations of DR2b and DR2a, the researchers made it possible to observe how the two genes interact to affect severity of MS symptoms.

They found that the mice engineered to carry only the DR2b had a severe form of MS that is seen in a minority of human MS patients. The mice with both genes, however, were less likely to get MS in the first place and had a less severe form of MS if they did, this resembles the most common form of MS in humans. In some cases, these mice spontaneously recovered. The researchers concluded that DR2b was the MS ‘culprit’ and DR2a cancelled out some of its effects.

As well as evidence that there is interaction between the two genes, whereby DR2a influences DR2b, the research also revealed the role of each gene in predisposition to MS.

Further analysis revealed each gene’s precise influence over the immune system and thus their respective roles in causing and abating MS symptoms.

The researchers are hopeful that exploiting DR2a’s control mechanism could be a way to treat MS symptoms in the future.

Professor Fugger said: 'This is a new way to assess how genes contribute to autoimmune diseases overall. Thus, this study is not only relevant to understand how genes interact in MS, but also in diabetes, rheumatoid arthritis and psoriasis which are all autoimmune diseases'

For further information or to arrange an interview with Dr Fugger please contact the MRC Press Office on 0207 637 6011, or out of hours on 07818 428 297.

Notes to Editors

1.Functional epistasis on a common MHC haplotype associated with multiple sclerosis is published online in Nature on 27th September 2006.

2.Around 85,000 people in the UK have Multiple Sclerosis. MS is the result of damage to myelin, a protective sheath surrounding nerve fibres of the central nervous system, due to myelin being attacked by the immune system. When myelin is damaged, messages between the brain and other parts of the body are inhibited. MS is a lifelong condition with a wide range of symptoms including pain, muscle problems, impaired cognitive function, and impaired vision.

3.The precise cause of MS is not known and many factors, both environmental and genetic, are understood to be involved. Around two-thirds of MS sufferers have the DR2 pair of genes. Having the DR2 pair of genes does not automatically mean an individual will have MS.

4.The Medical Research Council (MRC) is funded by the UK tax-payer. It aims to improve human health. The research it supports and the scientists it trains meet the needs of the health services, the pharmaceutical and other health-related industries and universities. The MRC has funded work which has led to some of the most significant discoveries and achievements in medicine in the UK.

5.The Wellcome Trust also supported part of this research: The Wellcome Trust is the most diverse biomedical research charity in the world, spending about £450 million every year both in the UK and internationally to support and promote research that will improve the health of humans and animals. The Trust was established under the will of Sir Henry Wellcome, and is funded from a private endowment, which is managed with long-term stability and growth in mind.

©2006 Medical Research Council