It's been three decades since the first treatment for multiple sclerosis (MS) was approved. In that time, the field has made substantial advances — including the approval of over two dozen medications — but there's still a long way to go to improve care for progressive forms of the disease and make therapies more easily accessible to patients worldwide. That's according to a pair of scientists with the Icahn School of Medicine at Mount Sinai, who published a personal viewpoint discussing the progress that's been made in treating MS, as well as highlighting areas where more work is urgently needed. The paper, "MS becomes a treatable disease: 30 years later," was published in the Multiple Sclerosis Journal. Betaseron's arrival spurred research and pharmaceutical interest in MS. The first disease-modifying treatment (DMT) for MS, Betaseron (interferon beta-1b), was approved in the U.S. in 1993, with approvals quickly following in other countries. This marked a seminal moment, as MS finally became a treatable disease. One of the paper's co-authors, Fred Lublin, MD, was involved in the early clinical trials that led to the therapy's approval, and wrote that this moment "remains the single most exciting event of my professional career." Approval of a first therapy spurred renewed interest in the disease from the pharmaceutical industry, while clinicians and researchers launched initiatives aiming to better characterize and diagnose MS. "International collaborations rapidly developed such that there was a world-wide effort at studying MS and broader aspects of human neuroimmunology, including improved clinical trial design," the researchers wrote. In the 30 years since, more than two dozen therapies have been approved to treat relapsing forms of MS, which are characterized by relapses, or periods where disease symptoms rapidly worsen or new ones appear, followed by periods of remission where symptoms ease. The availability of so many therapies, as well as a greater understanding of disease biomarkers, has meaningfully improved patients' lives. In the absence of treatment, people largely had to wait and hope they might not worsen too quickly. Now it's possible for people diagnosed with relapsing MS and given proper treatment to go years without any disease activity. But the advent of new treatments also created challenges, with clinicians and patients needing to consider the relative risks and benefits of different approaches. "Advancements in MS therapies led a generation of neurologists to truly grapple with risk and benefit ... and forced MS neurologists to become not just skilled diagnosticians but skilled tacticians in equal measure," the researchers wrote. Substantially less success is evident when it comes to treating progressive forms of MS, where symptoms gradually worsen over time independent of relapse activity. With progressive MS, it's 'almost like 30 years ago all over again' Most people who initially develop relapsing-remitting MS will eventually develop secondary progressive MS (SPMS), and a minority of MS patients have disease progression from the time it's first diagnosed, known as primary progressive MS (PPMS). It's thought that active inflammation drives relapse activity, which is why all approved therapies for relapsing MS work by reducing inflammation. However, the mechanisms that drive disease worsening in progressive MS are poorly understood, and treatment options are scant. "For the patient in the clinic with early relapsing MS, the treatment opportunities are numerous, the prognosis optimistic," the researchers wrote. "For the patient with advanced, progressive MS, all of those vaunted successes fall away, and it is almost like 30 years ago all over again. "We must focus our attention and research efforts on the widening chasm — of both mechanistic understanding and treatment efficacy — between these triumphs in relapsing MS and the desolation of MS progression, which still remains largely beyond our grasp," they added. Disease fundamentals also are continuing topics of debate, from the specific immune cells — like T- or B-cells — that drive MS to the role of the Epstein-Barr virus or other viral infections in disease development. "How could we have accomplished so much and still have such foundational questions remain unanswered?," the scientists wrote. In addition to these fundamentals and the gap in care between relapsing and progressive MS patients, the researchers noted that access to care remains a substantial issue. "Due to their high cost, MS DMTs have been particularly subject to inconsistent and unequal distribution, and the great progress in the treatment of relapsing MS has — unfortunately — largely benefitted those living in high-income countries," they wrote. The scientists called for more efforts to improve the equality of treatment access, writing that "no one with MS should be forced to live in a perennial pre-treatment era."