It was identify the first genetic marker responsible for the progression of multiple sclerosis. The discovery, published in Natureis the result of an international multicenter study involving over 70 institutions, led by researchers at the University of California San Francisco Parnassus Campus, in the United States and the University of Cambridge, in the United Kingdom, and with whom it collaborated in Italy, l University of Eastern Piedmont, the IRCCS San Raffaele Hospital of Milan, the University of Milan, the IRCCS Casa Sollievo della Sofferenza Foundation and the ASST Santi Paolo e Carlo of Milan.
The study, conducted on more than 22,000 people with multiple sclerosis, discovered the first genetic variant associated with a faster course of the disease, which over time can deprive patients of their mobility and independence. Multiple sclerosis occurs due to a failure in the immune system; this mistakenly attacks the brain and spinal cord causing flare-ups of symptoms, known as relapses, and long-term degeneration. The disease is degenerative and causes an accumulation of disability in the patient. Despite the development of effective treatments for relapses, none can reliably prevent progression. The discovery provides the first real leap in understanding and combating this aspect of multiple sclerosis and opens the door to long-term disability treatments. ‘Inheriting this genetic variant from both parents accelerates the moment of needing a walking aid by almost four years,’ said Professor Sergio Baranzini of the University of California San Francisco Parnassus Campus, co-author of the study.
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“Understanding how the variant affects MS severity will hopefully pave the way for a new generation of treatments that can prevent disease progressionsaid Professor Stephen Sawcer of the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, co-author of the study. Previous studies have shown that the susceptibility or risk of multiple sclerosis derives largely from immune system dysfunctions and some of these dysfunctions can be treated, slowing the disease. “These risk factors don’t explain why, ten years after diagnosis, some people with multiple sclerosis are in wheelchairs while others continue to run marathons,” explained Baranzini. To investigate the course of multiple sclerosis, two large research consortia, the International Multiple Sclerosis Genetics Consortium and the MultipleMS Consortium, have joined forces. The two institutions have integrated data from more than 12,000 people with multiple sclerosis to complete a genome-wide association study (GWAS), which uses statistics to accurately associate genetic variants with particular traits. In this case, the traits of interest correlated with the severity of multiple sclerosis, explaining, for example, the years from diagnosis to a certain level of disability. After sifting through more than seven million genetic variants, the scientists found one that was associated with faster disease progression. The variant lies between two genes that have never been linked to multiple sclerosis, called DYSF and ZNF638. The former is involved in repairing damaged cells and the latter helps control viral infections. The proximity of the variant to these genes suggests that they may be involved in disease progression.
“These genes are normally active in the brain and spinal cord, rather than in the immune system,” said Dr Adil Harroud, the study’s lead author and former postdoctoral researcher at the Baranzini Laboratory. “Our findings suggest that resilience and repair in the nervous system determine the course of progression of multiple sclerosis and that we should focus on these aspects of human biology for better therapies,” Harroud continued. The results of this study are the first clues to address the component of nervous system of multiple sclerosis. “Although it seems obvious that the brain’s resilience to injury would determine the severity of a disease like multiple sclerosis, this new study has pointed us towards the key processes that underlie this resilience,” Sawcer said. “This work represents an important breakthrough in the field of precision medicine, as it could, for example, lead to the use of more aggressive therapies from the outset in those patients with genetic variants unfavorable for progression”, they underlined the Italian researchers, Sandra D’Alfonso, Filippo Martinelli Boneschi and Federica Esposito.
Lucrezia Parpaglioni