Eliot seemed to have a charmed life. The 29-year-old had graduated from Stanford University and Harvard Business School, and then went on to a promising career on Wall Street. Married, his wife was six months pregnant. And he always had been health.
But Eliot, who asked to have his last name withheld, had been noticing strange symptoms, including numbness and tingling in his limbs. His primary care provider had ordered magnetic resonance imaging (MRI) and then called to say that the results could be multiple sclerosis (MS).
Eliot did not fit the profile of the typical MS patient: Ms is a degenerative disease of the brain and spinal cord that is often diagnosed in women and people over 40. When Eliot’s doctor suggested that he see a specialist, a physician friend recommended the Yale Medicine Multiple Sclerosis Center.
Confirming the diagnosis
Dr. Hafler’s suspicions had been raised by another symptom that came out with careful questioning. In addition to the numbness, Eliot had experienced temporary vision loss that had returned almost—but not quite—to normal. An abnormal MRI scan, followed by a spinal tap, confirmed the doctors’ suspicions. This was MS.
MS can have unpredictable and debilitating symptoms, but Dr. Hafler assured Eliot that he would be able to help him. New therapies, including many pioneered by his own laboratory, have become remarkably effective at halting or slowing the progression of the disease—and Eliot had caught his case early.
“We started him on one of the newer oral drugs, Tecfidera,” says
Dr. Hafler. “He takes it twice a day, with little in the way of side effects. We started doing MRIs every six months, and now do them every year. And the MS has never come back.”
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The genetic connection
For years, medical researchers have been working to identify the genetic causes of MS. Dr. Hafler, a founding member of the International Multiple Sclerosis Genetic Consortium, has devoted his life’s work to the intersection of genetics and immunology, the study of how the body’s immune system works. Immune system imbalances can lead to conditions like MS.
“When we started, people had been trying to crack the genetic cause of MS for decades,” says Dr. Hafler. “It hadn’t gone anywhere.”
There was much debate over whether the condition was neurodegenerative (caused by the destruction of brain tissue) or immunologic (caused by the immune system attacking the central nervous system).
When new genetic mapping technology came out, Dr. Hafler and his team began submitting the genes of MS to be mapped, to see whether that would give them a better understanding of the causes.
When results came back from the technicians, Dr. Hafler and his team were amazed to find that the genes that pertained to MS were indeed connected to the immune system.
“We can now say that MS is clustered with other autoimmune diseases,” says Dr. Hafler.
The genes related to MS cause the body to have an autoimmune response, or to attack its own cells—in this case, the cells of the myelin sheath, the protective covering of nerve fibers in the brain and spine.
That attack, and the resulting damage, is what causes symptoms such as those Eliot had mentioned to Dr. Hafler, numbness and vision problems chief among them.
A dozen treatments
Establishing this link between MS and the immune system has helped researchers identify genetic pathways that drug treatments might target—the same ones that activate the autoimmune response.
The best way to think of the research, then, is as a working model—of the body, the immune system and the genes. “You can’t get to the cures without knowing the basis of the disease,” says Dr. Hafler. “That to me is the story of the understanding of the disease. That’s led to treatment."
These years of experimentation, research and clinical trials have resulted in 12 different treatments, including oral drugs like Tecfidera, which reduces inflammation; Copaxone, which blocks the cells that damage myelin, the insulation for nerve fibers in the brain and spinal cord; and interferon, which protects cells from viral infections and can reduce brain lesions.
Dr. Hafler and his team are now studying checkpoint inhibitors, which essentially turn off overactive parts of the immune system, allowing the system to “fight back” against the disease.
Still, this is only the beginning: Autoimmune diseases affect 15 percent of the population, says Dr. Hafler, who hopes to expand the list of diseases that have similarly good prognoses.
Even as Dr. Hafler plans to test how checkpoint inhibitors might help treat cancer and Alzheimer’s patients, he and his colleagues keep their focus on MS, in an effort to develop therapies for the patients whose disease has already advanced.
Thanks to the strides they have made, more patients whose MS is diagnosed early are able to prevent deterioration. Eliot is a perfect example: Instead of suffering relapses, he is a health, active dad.