Spotlighting Advancements in MS Research

In a major research breakthrough at the University of Miami Miller School of Medicine, optic neuritis, or inflammation of the optic nerve, was revealed to be a common first symptom of multiple sclerosis (MS) among Hispano/Latinos with Native American ancestry.

Jacob L. McCauley, Ph.D., associate professor in the Dr. John T. Macdonald Foundation Department of Human Genetics and director of the Center for Genome Technology and its biorepository facility at the John P. Hussman Institute for Human Genomics, and his colleagues also identified four new genes that contribute to MS risk.

Jacob L. McCauley, Ph.D., associate professor
Jacob L. McCauley, Ph.D., associate professor in the Dr. John T. Macdonald Foundation Department of Human Genetics at the University of Miami Miller School of Medicine

“I’m very excited about both of these studies,” Dr. McCauley said. “Pinpointing the causes and initial symptoms of MS has real-world applications that can, down the road, guide other researchers in the development of therapeutic targets and allow for earlier diagnoses in clinical settings.”

Previous work by the International Multiple Sclerosis Genetics Consortium (IMSGC), of which Dr. McCauley is a member, has identified 233 genetic risk variants for MS, a disabling autoimmune disorder. Together, these 233 genetic risk variants account for only about 20 percent of overall disease risk, so IMSGC knew there must be more genes.

To find them, IMSGC members pooled more than 68,000 MS patients and control subjects from the United States, Australia, and 10 European countries to look for rare variants that damage the gene sequence directly. They found four new genes, each of which acts independently as a risk factor for MS, which they report in the journal Cell.

“The four genes we discovered explain another 5 percent of MS risk,” Dr. McCauley said. “We used a much larger sample size than previous studies, which was what made the search for rare genetic variants possible.”

Accounting for 25 percent of the risk for developing MS is a major breakthrough. The 233 genetic risk variants mentioned earlier explain about 0.09 percent each, on average. The newly discovered genes explain about 1.25 percent of MS risk each, on average, which makes them better predictors.

close photo of one eye

To achieve the other research breakthrough, Dr. McCauley and his colleagues obtained data from 1,033 self-identified Hispanic/Latino individuals with MS from an ongoing study by the University of Southern California; the University of Miami; the University of California, San Francisco; and the San Juan MS Center. The team analyzed information on genetic ancestry, age at MS onset, and the occurrence of optic neuritis to uncover relationships among these variables.

Optic neuritis, or inflammation of the optic nerve, can cause blurring or graying of vision, blindness in one eye, or a scotoma (a dark spot in your field of vision).

“For people of Native American ancestry, optic neuritis is far more common as a first symptom of MS,” Dr. McCauley said. “They also tend to be younger when MS first presents.”

The study, which was published in the Annals of Clinical and Translational Neurology, suggests that genetics can underlie clinical differences in people of different ethnic backgrounds. Therefore, it may behoove clinicians to pay closer attention to visual symptoms that hint at MS if they practice in the southwestern United States, where Native American ancestry is common among Hispanics/Latinos.

“We will continue to explore these differences as we attempt to explain how and why MS occurs,” Dr. McCauley said. “If we could answer these questions more fully, we could set pharmaceutical researchers on the right path.”

Tags: Jacob L. McCauley, MS, multiple sclerosis