Research led by scientists at the Universities of Oxford, Cambridge, Copenhagen, Bristol and California (Berkeley) reveals the evolutionary origins of multiple sclerosis (MS). This new insight into the genetic architecture of this disease changes scientists view of its causes and has implications for its treatment, as well as paving the way for further investigations into other diseases. <\/p>\n
Affecting 1 in 1,000 people, multiple sclerosis (MS) is an autoimmune disease in which the body's immune system attacks its own brain and spinal cord. Northern Europe has the highest prevalence of MS in the world. <\/p>\n
The new research published in Nature draws on analysis of the DNA of ancient human bones and teeth held in museum collections across Europe and Western Asia. It reveals that a major migration of pastoralist herders known as the Yamnaya people from from the Pontic Steppe (a region spanning parts of what are now Ukraine, South-West Russia and the West Kazakhstan) into Western Europe 5,000 years ago introduced genetic variants into the population. <\/p>\n
These new variants provided an advantage to the people carrying them at the time, probably by providing protection against infectious diseases in their domesticated animals. In today's modern environment, however, these same genetic variants increase the risk of developing MS. <\/p>\n
To show this, the research team compared data held in a unique gene bank of ancient DNA to the UK Biobank, a large-scale biomedical database and research resource containing genetic, lifestyle and health information and biological samples from half a million UK participants. The research was funded by a 8M grant from the Lundbeck Foundation. <\/p>\n
The new insights into the genetic factors behind MS are helping to demystify the disease, which is crucial, stresses co-author Professor Lars Fugger of the MRC Weatherall Institute of Molecular Medicine and Nuffield Department of Clinical Neurosciences at the University of Oxford. <\/p>\n
'This is very important from the perspective of both patients and doctors. Because it means that we can do away with the conventional perception of MS, which defines the disease in terms of the impairments it causes, and instead understand and seek to treat MS for what it actually is: the result of a genetic adaptation to certain environmental conditions that occurred back in our prehistory and which has endured in our DNA, even though the environmental conditions have changed hugely in the time between then and now,' Professor Fugger explains. <\/p>\n
For more than three decades, as a professor and consultant physician at the Oxford University Hospitals NHS Foundation Trust, Professor Fugger has been conducting research into MS and treating patients with immune-mediated disorders. So far, 233 MS-genetic risk variants have been mapped. The findings presented in the new paper show that many of these genetic variants provided protection against infectious diseases. There is no immediate indication that they held any disadvantage at that time, Fugger explains: <\/p>\n
'The situation today is different because the diseases these variants originally provided protection against are no longer as big a problem as they likely were then. Because in the intervening millennia, we have antibiotics, vaccinations and far, far higher standards of hygiene than people had thousands of years ago. Thus, the risk genes are now \"miscast\" in terms of their original biological role.' <\/p>\n
Science so far has 'only an incomplete understanding of why individuals develop MS', co-author Professor Astrid Iversen explains. A professor of virology and immunology at the MRC WIMM and Nuffield Department of Clinical Neurosciences at the University of Oxford, her research concerns the evolutionary processes in the development of the human immune response to challenges from pathogens, meaning the bacteria and viruses that cause disease. <\/p>\n
Based on archaeological DNA, Professor Iversen is also investigating how pathogens interacting with environmental and lifestyle factors ever since the the Last Ice Age have impacted the immune system of present-day individuals and their genetic susceptibility to certain diseases, including autoimmune diseases like MS, which have been on the rise over the last 50 years. <\/p>\n
'The selection process involving the human immune system is ongoing, meaning it is also happening right now,' explains Professor Iversen, adding: 'The individuals who have immune system genes that allow them to fight off the combination of infectious diseases they are exposed to in life will have children who pass on those same immune system genes. This is why the immune system in all present-day individuals is also, genetically speaking, the product of selection processes our ancestors underwent. But because we now lead very different lives to those of our ancestors in terms of hygiene, diet, medical treatment options for, for example, some parasitic diseases, as a result of our evolutionary history, we may, in some respects be more susceptible to certain diseases than our ancestors were, including autoimmune diseases such as MS.' <\/p>\n
Professor Fugger explains how the research findings hold some promise for future treatment: 'MS is an autoimmune disease, and a lot of the drugs we currently use to treat it target the immune system. The downside is that we risk suppressing the immune system so effectively that patients are less well equipped to fight infections. <\/p>\n
'What we need is an approach whereby we can learn from more studies on the genetic background of MS how to 'recalibrate' the immune system in patients. This would allow their immune system to play an active role in suppressing the disease. While that's not just around the corner, it's still what we should be aiming for in terms of research.' <\/p>\n
This MS study demonstrates that the large ancient human genome data sets, combined with analyses of present-day DNA and input from a number of other research fields, serve as a scientific precision tool capable of providing new insights into diseases. <\/p>\n
The international research team now plans to investigate other neurological conditions including Parkinson's and Alzheimer's diseases, and psychiatric disorders including ADHD and schizophrenia. <\/p>\n
The paper, 'Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations', is published in Nature. <\/p>\n
<\/p>\n
Original post: Research led by scientists at the Universities of Oxford, Cambridge, Copenhagen, Bristol and California (Berkeley) reveals the evolutionary origins of multiple sclerosis (MS). This new insight into the genetic architecture of this disease changes scientists view of its causes and has implications for its treatment, as well as paving the way for further investigations into other diseases. Affecting 1 in 1,000 people, multiple sclerosis (MS) is an autoimmune disease in which the body's immune system attacks its own brain and spinal cord. Continue reading
\nResearch into ancient DNA sheds new light on cause of Multiple Sclerosis and other neurodegenerative diseases - University of Oxford<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"