Researchers Identify Genes With Potential to Predict Progression and Severity of MS

Researchers have identified complement genes that appear to play a role in vision loss associated with multiple sclerosis (MS), and this finding could help researchers monitor and predict the progression and severity of MS, according to a study published in Brain.

Even though previous studies have identified gene variants associated with the risk of developing MS, until now, there have been no identified gene variants associated with MS severity.

“Multiple sclerosis is a heterogeneous disease with an unpredictable course and a wide range of severity; some individuals rapidly progress to a disabled state whereas others experience only mild symptoms,” the authors explained.

In 374 patients with all types of MS, the researchers used an imaging technique that allows them to assess damage to the nerve cells in the retina. Patients underwent an average of 4.6 scans between 2010 and 2017, and the authors reported that the rate of deterioration was a loss of 0.32 micrometers of tissue per year per patient, on average.

After they identified the patients who had the fastest deterioration rates, the researchers collected DNA through blood samples to identify genetic mutations. They identified 23 DNA variations that mapped to the complement gene C3.

Once they identified the variants, they analyzed DNA from blood samples of 835 patients with MS in an existing clinical trial who underwent periodic vision testing. The researchers noted genetic changes in the complement genes C1QA and CR1 in patients whose ability declined the fastest in the vision tests. Patients with mutations in C1QA were 71% more likely to develop difficulty with the vision test and patients with changes in CR1 were 40% more likely.

The authors plan to repeat the studies in larger populations and conduct animal studies investigating the function of complement proteins to better understand the mechanism behind their ability to kill nerve cells in patients with MS.

"Although we have treatments for the type of MS where symptoms come on in bursts—called relapsing-remitting MS—we don't have any way to stop the kind of MS in which the nerve cells start to die, known as progressive MS," Peter Calabresi, MD, professor of neurology and neuroscience at the Johns Hopkins University School of Medicine and codirector of the Johns Hopkins Precision Medicine Center of Excellence for Multiple Sclerosis, said in a statement. "We believe that our study opens up a new line of investigation targeting complement genes as a potential way to treat disease progression and nerve cell death."

Reference

Fitzgerald KC, Kim K, Matthew D Smith, Aston SA, et al. Early complement genes are associated with visual system degeneration in multiple sclerosis. Brain, 2019; 142(9):2722. doi: 10.1093/brain/awz188.