A study of more than 22,000 people with multiple sclerosis has discovered the first genetic variant responsible for a more rapid progression of the disease, which can deprive patients of their mobility and independence over time.
The finding represents the first progress in understanding the progressive deterioration associated with multiple sclerosis and opens the way for the study of treatments that can prevent it.
In this neurodegenerative disease, the immune system mistakenly attacks the brain and spinal cord. Outbreaks known as relapses occur, as well as long-term degeneration. Although effective treatments against relapse have been developed, none is significantly effective against the accumulation of disability.
In other words, the disease can be slowed down with treatments against part of the immune system dysfunction, but it is unknown why patients evolve at such different speeds. Why, ten years after diagnosis, some are in a wheelchair. One explanation is in the genes.
“The work has identified a genetic variant that advances disability by 3.5 years, the time in which the patient will need help to walk,” explains Sara Llufriu, head of the Advanced Imaging group in neuroimmunological diseases at Idibaps and a of the 70 researchers from around the world who have participated in the study.
Scientists found the marker indicating faster disease progression after examining more than seven million genetic variants. It is located between two genes with no previous connection to multiple sclerosis, called DYSF (involved in repairing damaged cells) and ZNF638 (helps control viral infections).
These genes are normally active within the brain and spinal cord, rather than the immune system. “We must continue studying how they act and how they affect the nervous system in general,” says Llufriu. “Although it seems obvious that the brain’s resilience to injury would determine the severity of a disease such as multiple sclerosis, this new study has pointed us to the key processes underlying this resilience,” the researchers say.
The next step is to deepen the study of the genes that make the cells of the nervous system less resilient, says Llufriu. According to the researcher, it is part of the path towards finding therapies that prevent or delay the neurodegeneration caused by multiple sclerosis, which is “more feasible than finding drugs that can reverse the damage caused by neurodegeneration.”
Published this Wednesday in Nature, the work is the product of a collaboration of more than 70 institutions from around the world and hundreds of researchers, led by the University of Cambridge and UCSF (USA). Members of the Hospital Clínic and Idibaps (Yolanda Blanco, Sara Llufriu and Albert Saiz) and the Center for Multiple Sclerosi de Cataunya (Xavier Montalban, Manuel Comabella, Sunny Malhorta and Luciana Midaglia) have participated.
The work has brought together the two major global multiple sclerosis research consortia, which have combined data from thousands of patients on the severity of the disease, including the years elapsed for each individual from diagnosis to a certain level of disability. .
