MS Progression Genetic Breakthrough: New Discovery Paves the Way for Treatment

Progression of MS Acceleration: Genetic Breakthrough Offers Potential Treatment Avenues

In a remarkable advancement, researchers have unveiled a groundbreaking genetic revelation linked to the hastened progression of multiple sclerosis (MS), a discovery that could potentially lead to earlier implementation of walking aids for patients. This crucial breakthrough, achieved through a collaborative global effort, underscores the significance of the nervous system’s resilience in dictating the trajectory of the disease’s advancement and hints at potential external factors influencing the severity of MS.

Milestone Discovery: Genetic Indicator for Multiple Sclerosis Severity Unveiled

A pioneering study encompassing a vast cohort of over 22,000 individuals grappling with multiple sclerosis (MS) has unearthed a pivotal genetic variant intricately tied to the accelerated advancement of the ailment. This swift deterioration profoundly impacts patients, impeding their mobility and independence as the disease progresses.

Multiple sclerosis is an autoimmune disorder characterized by the immune system’s erroneous assault on the brain and spinal cord. This assault manifests through intermittent bouts of symptoms known as relapses, along with a prolonged degenerative process termed progression. While considerable strides have been made in treating relapses, with notable contributions stemming from the University of Cambridge, a dependable means to halt the progression of disability remains an elusive goal.

Global Cooperation Yields Genetic Milestone

In a recent publication within the esteemed journal Nature, an alliance of international scientists divulges a genetic variant that amplifies the severity of the disease, marking the initial substantive advancement in comprehending and eventually combatting this facet of MS.

This accomplishment is the result of a vast global consortium comprising more than 70 institutions spanning the globe, spearheaded by experts from UCSF (USA) and the University of Cambridge (UK).

“Inheriting this genetic variant from both parents accelerates the time to needing a walking aid by almost four years,” affirmed Professor Sergio Baranzini of UCSF, a co-senior author of the study.

“Elucidating the mechanisms through which this variant influences MS severity may potentially pave the way for an innovative generation of treatments designed to impede disease progression,” added Professor Stephen Sawcer from the University of Cambridge and the Cambridge University Hospitals NHS Foundation Trust, the other co-senior author of this seminal study.

Decoding MS: Genetic Insights and Implications

To unravel the enigma surrounding the severity of MS, two prominent MS research consortia united their efforts: The International Multiple Sclerosis Genetics Consortium (IMSGC) and The MultipleMS Consortium. This strategic collaboration empowered MS researchers worldwide to pool their resources and initiate the identification of genetic elements dictating the outcomes of MS.

Previous studies have underscored that susceptibility to MS, or the risk of its development, is primarily rooted in immune system dysfunction, with certain instances of such dysfunction being treatable and capable of decelerating the disease. However, as Baranzini elucidates, “these risk factors fail to elucidate why, a decade after diagnosis, some MS patients rely on wheelchairs while others continue to participate in marathons.”

By amalgamating data from over 12,000 MS-afflicted individuals, the two consortia conducted a genome-wide association study (GWAS), a statistical technique meticulously correlating genetic variants with specific traits. In this context, the traits of interest revolved around the severity of MS, including the duration each individual required to progress from diagnosis to a certain level of disability.

Genetic Markers and the Course of MS Progression

Following an exhaustive examination of over seven million genetic variants, researchers unearthed a solitary variant connected with hastened disease progression. Positioned between two genes previously unassociated with MS, labeled DYSF and ZNF638, this variant’s proximity to these genes suggests their plausible involvement in disease progression.

“Normal activity of these genes occurs within the brain and spinal cord, rather than the immune system,” as affirmed by Dr. Adil Harroud, the lead author of the study and a former postdoctoral researcher in the Baranzini Lab. “Our findings propose that the resilience and reparative capabilities of the nervous system ascertain the trajectory of MS progression, prompting us to focus on these aspects of human biology to formulate improved therapeutic approaches.”

These findings represent the first critical leads in addressing the nervous system component of MS.

Employing statistical methodologies termed ‘Mendelian randomization,’ the team further explored the influence of environmental factors. Their investigation revealed that higher levels of education and advanced parental age mitigate the severity of MS, while smoking exacerbates it. These associations with indirect metrics of brain health underscore the paramount importance of resilience in determining the outcomes of MS.

“Although the notion that the brain’s capacity to withstand injury shapes the severity of diseases like MS appears evident, this recent study guides us toward the fundamental processes underlying such resilience,” concluded Sawcer.

Advancing MS Understanding and Treatment

To validate their discoveries, researchers extended their genetic scrutiny to an additional pool of nearly 10,000 MS patients. Those possessing two copies of the identified variant displayed a swifter journey towards disability.

Subsequent research will be imperative to decipher precisely how this genetic variant influences DYSF, ZNF638, and the broader nervous system. Simultaneously, researchers are amassing an even larger collection of DNA samples from individuals affected by MS, with expectations of uncovering other variants contributing to sustained disability in this condition.

Harroud articulated, “This ushers in a new prospect for developing novel drugs capable of preserving the well-being of all afflicted by MS.”

The exploration of multiple sclerosis genetics has been a predominant pursuit in neurological research at Cambridge since the late 1980s. Collaborating with other experts, members of the Department of Clinical Neurosciences have played a pivotal role in unveiling the majority of gene variants responsible for heightened susceptibility.

Professor Alastair Compston from the University of Cambridge, a founding member of the IMSGC, commented, “Having been intricately involved in identifying susceptibility genes for multiple sclerosis since the 1970s, the discovery of fully independent risk variants for progression is a testament to the endeavors of those within IMSGC who spearheaded this project.”

He further accentuated, “Once again, this work underscores the dividends of international collaboration in advancing the understanding of disease mechanisms not only in multiple sclerosis but also in other medical conditions.”

For further insights into this study:

Genetic Breakthrough: Unraveling Factors Intensifying Multiple Sclerosis
Delving into the Genetic Variant Propelling Swift Progression of Multiple Sclerosis

Reference: “Locus for severity implicates CNS resilience in the progression of multiple sclerosis” by International Multiple Sclerosis Genetics Consortium and MultipleMS Consortium, 28 June 2023, Nature.
DOI: 10.1038/s41586-023-06250-x

This endeavor received partial support from the National Institutes of Health/National Institute of Neurological Disorders and Stroke, the European Union’s Horizon 2020 Research and Innovation Funding Programme, and the Multiple Sclerosis Society of Canada.

Frequently Asked Questions (FAQs) about MS Progression Genetic Variant

More about MS Progression Genetic Variant

• Nature article: Genetic Breakthrough in MS Progression
• University of California, San Francisco (UCSF) news release: UCSF Research Team’s Findings on MS Progression
• University of Cambridge Department of Clinical Neurosciences: MS Research and Genetic Discoveries
• International Multiple Sclerosis Genetics Consortium (IMSGC): Collaborative Efforts in MS Research