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MILAN -- A path to a cure for multiple sclerosis (MS) may be on the horizon, a top MS researcher suggested.

The field faces a great opportunity to advance from suppressing the disease to curing it, said Stephen Hauser, MD, of the University of California San Francisco, in the keynote speech at the joint meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

Major advances in treating MS have emerged since neurologists first started holding meetings to discuss research about the disease some 40 years ago, Hauser noted.

Although gains in treating MS have been substantial, three areas hold prospects for progress: treating early; realizing that a cure is realistic, especially in some scenarios; and understanding that MS drivers are heterogeneous and will require targeting multiple cell types, which will be guided by pathology and bedside investigations.

The earlier we treat, the more likely we are to have a large response, Hauser noted. "The autoimmune response is more focused, but we've made little progress thus far in identifying the earliest MS triggers with specificity," he said. "The earlier we can intervene, the greater the likelihood of achieving maximum, and possibly complete, control."

Genetics may contribute incrementally to identifying early MS, but a specific MS signature has been lacking, Hauser said. "There are 230 loci that influence MS susceptibility," he pointed out. However, earlier this year, a newly-identified variant associated with MS severity was identified, rs10191329 in the DYSF–ZNF638 locus, Hauser added.

Intervention at clinical onset is the low-hanging fruit, and intervening at the presymptomatic stage may become possible with new tools and markers.

Treatment benefits have been seen in the earliest MS stages in the ARISE and TERIS studies of radiologically isolated syndrome and the and trials in clinically isolated syndrome, Hauser noted. A subset of MS patients have a humoral immune signature years before diagnosis, and new research has shown that a cluster of MS patients had a over time.

A cure is realistic, especially for some scenarios, but a working definition is needed, he added.

"We have an immense opportunity to advance from partial to complete suppression to cure," Hauser said. "Foremost, I think, is the importance of having biomarkers -- imaging, protein, genetic, and immune biomarkers of cell-type specific myelin damage."

"We should take the lead from cancer therapeutics," he noted. A complete response in B-cell leukemia, for example, is based on no evidence of disease, off-treatment, for 4 years. "A complete response equivalent for MS could be developed, also," Hauser said. "I think a cornerstone of this could be normalization of cerebrospinal fluid."

New markers and tools will help address other clinical questions, including moving beyond disease suppression to defining a cure. Next-generation therapeutics may need to neutralize multiple cell types, including treatment-resistant B cells, microglia, and CD8+ T cells.

"Thanks to our entire community, MS is one of the two or three great success stories of modern molecular medicine," he said. "We're halfway home, but we're not all the way there."

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