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Ohio Team Identifies SNP Tied to Increased MS Risk, Progression

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Researchers from Ohio have identified a genetic mutation that may double an individual’s risk of developing multiple sclerosis and hasten its progression. If verified, the findings might present drug makers with a viable target, and help physicians better determine therapeutic strategies for their MS patients.

Investigators from the Ohio State University College of Medicine and Public Health focused on two versions of the CD24, which expresses a protein found on immune cells and influences immune responses.

Earlier work led by Yang Liu, a professor of pathology at OSU, showed that the CD24 protein is responsible in part for the development of experimental autoimmune encephalomyelitis in mice. For the new study, Liu and colleagues sought to learn whether CD24 was associated with the human disease. “Other investigators had discovered the SNP, but no one had linked the CD24 gene to MS or any other disease,” Liu said in a statement.

Specifically, the allegedly culpable mutation is believed to replace one amino acid, alanine, with another, valine, in the CD24 protein. The gene that encodes the alanine version of the protein is called CD24a; the valine version is called CD24v.

To learn whether the mutation is implicated in human MS, the researchers analyzed lymphocytes from 242 MS patients treated at the Ohio State University Multiple Sclerosis Center to determine if the person carried CD24a/a, CD24v/v, or CD24a/v genes. The team repeated the analysis on lymphocytes from 207 controls.

Liu’s team found that 13 percent of people with MS carried the CD24v/v genes, compared to 6 percent of controls; the differences represented about a two-fold increase in risk for MS, the researchers said. In addition, there was a “statistically significant tendency” for children with MS to have inherited the CD24v genes from parents who carried the CD24a/v forms. The study appears in the Dec. 9 issue of the Proceedings of the National Academy of Sciences.

“Our findings provide the first evidence that [the] CD24 gene is important in the development of MS,” Yang Liu, professor of pathology at OSU, said in a statement. “They also suggest that the protein encoded by this gene may provide a valuable target for new drugs to treat the disease.”

Lastly, the team noticed that of the individuals with MS, 112 had lost the ability to walk. Of these, 57 had CD24a/a genes, 40 had a/v genes, and 15 had v/v genes, the researchers reported. Additionally, the researchers found that half of the patients with CD24v/v lost the ability to walk within five years after their first symptoms appeared. Of those with CD24a/v genes, half lost that ability within 16 years, while individuals with CD24a/a genes lost the ability within 13 years. (The difference between CD24a/a and CD24a/v was not statistically significant, the team said.)

“The evidence from this study, together with the evidence from our animal studies, strongly suggests that CD24 could be an important new target for the treatment of multiple sclerosis,” Liu said in the statement.

—KL

 

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