A team of international researchers has identified 29 new genetic variants linked to multiple sclerosis, providing critical insight into the biology behind the debilitating neurological disease.
The research, which represents the largest MS genetics study ever undertaken, revealed that many of the genes implicated in the development of MS are relevant to the immune system, illuminating the possible immunological pathways that underlie MS.
The researchers said the newly-found links suggest that white blood cells known as T-cells, which are responsible mounting the body’s immune response, along with chemicals called interleukins play a vital role in the development of multiple sclerosis.
Multiple sclerosis is a crippling, but baffling, disease of the nervous system, and is one of the most common neurological conditions among young adults, affecting two and a half million people worldwide. The disease results from damage to nerve fibers and their protective insulation, the myelin sheath, in the brain and spinal cord. The affected pathways, which are responsible for everyday activities such as seeing, walking, feeling, thinking and controlling the bowel and bladder, are prevented from ‘firing’ properly and eventually are destroyed.
The current study’s findings shed light on the key role of the immune system in causing this damage, and help explain the nature of the immune attack on the brain and spinal cord.
The researchers studied the DNA from 9,772 individuals with multiple sclerosis and 17,376 unrelated healthy controls. They were able to confirm 23 previously known genetic associations and identified a further 29 new genetic variants (and an additional five that are strongly suspected) conferring susceptibility to the disease.
A large number of the genes implicated by these findings play pivotal roles in the workings of the immune system, specifically in the function of T-cells (a type of white blood cell involved in autoimmunity and in mounting the body’s immune response against foreign substances) as well as the activation of ‘interleukins’ (chemicals that ensure interactions between different types of immune cells).
Interestingly, one third of the genes identified in the study 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 general processes occur in more than one type of autoimmune disease.
Previous research has suggested a link between Vitamin D deficiency and an increased risk of multiple sclerosis. Along with the many genes that play a direct role in the immune system, the researchers identified two involved in the metabolism of Vitamin D, offering insight into a possible link between genetic and environmental risk factors.
“Identifying the basis for genetic susceptibility to any medical condition provides reliable insights into the disease mechanisms,” said Alastair Compston from the University of Cambridge, who co-led the study.
“Our research settles a longstanding debate on what happens first in the complex sequence of events that leads to disability in multiple sclerosis. It is now clear that multiple sclerosis is primarily an immunological disease. This has important implications for future treatment strategies,” Compston said.
Study co-leader Peter Donnelly from the Wellcome Trust Centre for Human Genetics, University of Oxford, said the research underscores the importance of large-scale genetic studies of common diseases.
“Our findings highlight the value of large genetic studies in uncovering key biological mechanisms underlying common human diseases. This would simply not have been possible without a large international network of collaborators, and the participation of many thousands of patients suffering from this debilitating disease,” Donnelly said.
There are several drugs in development that target the immune system, such as rituximab, sold under the brand name Rituxan by Roche and Biogen, Tysabri from Biogen and Elan, Lemtrada, sold as Campath by Genzyme, and Abbott and Biogen’s Zenapax.
“We have implicated genes that are highly relevant to the actions of those drugs,” said Compston.
“It is now clear that multiple sclerosis is primarily an immunological disease. This is the way to nail this disease and get on top of it,” Compston said.
The study, which included contributions from nearly 250 researchers as members of the International Multiple Sclerosis Genetics Consortium and the Wellcome Trust Case Control Consortium, was published online August 10, 2011, in the journal Nature.
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