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Distinguished neurologists Dr. Jonah Chan and Dr. Stephen Hauser confer at the UCSF Weill Institute for Neurosciences, an umbrella organization that links the clinical and basic neurosciences at UCSF to accelerate research against neurologic diseases including multiple sclerosis.

The problem

Multiple sclerosis (MS) is a complex illness in which the immune system injures the brain and spinal cord. The National MS Society estimates that nearly 1 million people in the United States and 2.3 million people globally live with MS.

The research, and progress to date

The UCSF EPIC and ORIGINS studies have carefully followed over 800 people with MS since 2004 with the purpose of understanding what triggers the disease, what causes it to progress, and how to prevent, remediate, and cure it.

The work has led to significant gains in the field’s understanding of how MS progresses over time.

Most importantly, the work has led to medical breakthroughs that have dramatically improved the quality of life for MS patients. The development and approval of new “B-cell” therapies to treat MS have proven to be extremely effective in preventing MS relapses. Double-blind studies demonstrate that these drugs (rituximab, ocrelizumab, and ofatumumab) stop development of new myelin scars responsible for MS relapses by 99%. Hal Barron, the Chief Medical Officer of Genentech at the time, described this near complete eradication of inflammation as “almost unbelievable…a treatment effect unequaled in modern therapeutics.”

These drugs have also proven to be effective in slowing the underlying progression of MS over time, reducing disability progression by ~30-40%.

“UCSF has been a driving force in the spectacular advances that have occurred for patients with multiple sclerosis. The EPIC and ORIGINS studies are the best example I know illustrating the power of connecting carefully studied patient cohorts with world class science. These studies have been central to identifying B cells as key actors in MS, transforming the field and leading to development of new life-changing therapies.”

Howard L. Weiner, MD, Robert L Kroc Professor of Neurology, Harvard Medical School, Director, Partners MS Center, Co-Director, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Boston, MA

What’s next

Moving forward, the UCSF team is focused on how to stop the residual progression of MS that can continue in some patients despite B cell therapy. The team is conducting trials to treat patients just as MS begins, before B cells establish permanent residence in the brain. Also, studies using higher doses of ocrelizumab and a new class of drugs (BTK inhibitors) are underway to measure the effect on progression.

The team is simultaneously seeking to understand what causes MS. They believe that a combination of environmental factors triggers an immunological cascade in genetically susceptible individuals that results in the clinical manifestations of MS. To find the triggers, they are studying a large cohort of individuals who are presenting with MS symptoms for the first time and using state of the art tools to identify the causative genetic, infectious, and immune factors.