On the Path to a Cure for MS

In many ways, Stephen Hauser ’71 was set on his life’s course at the age of eight, when his brother was born with severe brain damage. For the next several years, Hauser struggled to understand, to help, and to live with the family tragedy. When his brother passed away, he was left with a vaguely defined but persistent yearning to comprehend what had happened—both to his brother and to his best friend, who had died of a brain tumor several years earlier. What caused these terrible diseases of the brain?

Hauser’s search for answers led him to MIT for a chemistry degree, Harvard Medical School, and a career as a neuroimmunologist. Today, Hauser directs the Weill Institute for Neurosciences at the University of California, San Francisco, and is one of the world’s leading experts on multiple sclerosis (MS). He is responsible for major breakthroughs in the understanding and treatment of the disease.                                                                                                  

As he details in his 2023 book, The Face Laughs While the Brain Cries: The Education of a Doctor, Hauser was profoundly affected during his residency at Massachusetts General Hospital by seeing an accomplished 27-year-old Harvard Law School graduate struck down by MS. “I decided right there that this common, crippling disease of young adults would be my life’s work,” he writes.

At that time, in the 1970s, MS was still largely a mystery to medical science, with no treatments available that could change the course of the disease. Patients typically became disabled, in a wheelchair within 15 years of onset. Fortunately, the picture has come into better focus over the years. “MS is a very common disease caused by an overactive immune system,” Hauser explains. “It’s an autoimmune disease. Autoimmune diseases can affect any organ in the body. When it affects the joints, it’s rheumatoid arthritis, the pancreas, it’s diabetes.” When autoimmune disease affects the brain, he notes, it’s most often multiple sclerosis.

It took the development of the first laboratory model—by Hauser, in 1995—that faithfully recapitulated what happens in people with MS to point the way to better treatments. “The results overturned the current concepts, at the time, of the cause of MS, and pointed to an unexpected white blood cell called a B lymphocyte that was at the center of orchestrating the immune damage in MS,” Hauser says. Although the concept was firmly grounded in data, it was at first considered biologically implausible by most of the medical community. “It was out in left field in terms of contemporaneous thinking about multiple sclerosis and autoimmunity.” 

His discovery “pointed to the importance of these B cells in the bloodstream that move into the brain and orchestrate immune damage in MS, mostly due to an attack on the myelin covering of nerve cells.” Myelin insulates nerve cells and enables them to communicate efficiently with other cells. “When myelin is attacked by the immune system, the nerve cells short-circuit and ultimately die,” says Hauser. Building on the B cell connection led Hauser to the idea of therapies to kill B cells in the bloodstream and prevent them from moving into the brain. In 2006, he led a preliminary clinical trial of rituximab, a monoclonal antibody medication that had been approved by the FDA for treatment of B cell lymphoma, to test its effectiveness against the ravages of B cells in MS. The trial showed dramatic elimination of inflammation in MS patients, which meant “wonderful protection against brain damage for the nearly one million people in the US and the millions worldwide who have this disease.” Hauser later extended this success by leading a clinical trial for another more advanced monoclonal antibody called ocrelizumab, which displayed even better results, reducing brain inflammation by more than 99 percent. Thanks to Hauser’s work, both drugs are now part of the standard arsenal against MS.

Another important breakthrough made by Hauser was his discovery of how genetic factors play into the roots of MS and how they can help to identify people who may be at particular risk for developing the disease. Hauser began to explore this angle at MIT while working in the lab of Har Gobind Khorana. (Khorana won the 1968 Nobel Prize in Medicine for his work explaining how nucleotide sequences in genes are converted into proteins.) “That was an incredibly important experience for me and led directly to my work of over 30 years in understanding the genetics of multiple sclerosis,” Hauser says. 

Throughout his career, he continued researching how genetics impacts MS, noting that genetics is a vital part of understanding and fighting the disease. “It’s a complex disease, meaning that both genes and environment participate, and many genes play a role,” he says. In fact, Hauser says that more than 230 genes play a role in contributing to MS risk. “Many of these genes work through the cell that I had identified in the lab as critical to MS, the B cell. So, the genetic work and the environmental work and the immunology all came together in the discovery that B cell–based treatments were highly effective for MS patients.”

While Hauser went on to medical school, he is unequivocal about MIT’s influence on his life and career. “There was nothing in my education before or after that came close to the impact that MIT had on me,” he says. “It was life changing.” 

After decades of devoting himself to the study of MS, Hauser says he’s more optimistic than ever about the prospects for a cure. “I think we’re well on the way,” he says. “We first need to have complete disease suppression, and we’re not quite there yet.” However, Hauser noted, researchers have just completed enrollment of the first study testing if MS can be cured by aggressive treatment at the very dawn of disease. “I think everyone in the field is optimistic that this could happen,” he says.

He’s also confident about science making great strides in combating other devastating neurological diseases. “New technologies plus better disease models are opening the door for a better understanding and realistic prospects for therapies, preventions, repairs, and cures for people with brain diseases,” he says.

Photo illustration: Alumni Association staff; images Shutterstock.com/Dmytro Zinkevych.