World MS Day: Tackling Progressive Disease


Kathy Zackowski, PhD, OTR, associate vice president of research at the National MS Society, provided insight on the ongoing efforts to treat progressive MS, including strategies to develop remyelinating treatments.

Kathy Zackowski, PhD, OTR, associate vice president of research, National MS Society

Kathy Zackowski, PhD, OTR

World MS Day, held May 30th, is a global initiative bringing the multiple sclerosis (MS) community together to share stories, raise awareness, and campaign with those affected by the disease. MS, a disease that affects an estimated 2.5 million people worldwide, is categorized into 4 main types: relapsing-remitting (RRMS), primary progressive (PPMS), secondary-progressive (SPMS), and progressive-relapsing. The exact cause of MS is unknown, but research suggests it develops when an individual’s immune system attacks a substance called myelin.

One medication—ocrelizumab (Ocrevus; Genentech) has been approved by the FDA for the treatment of PPMS, as well as for relapsing forms of MS, including clinically isolated syndrome, RRMS, and SPMS. It remains the only disease-modifying therapy approved for this condition. In addition to other off-label options, there are symptom management and rehabilitation strategies that patients with PPMS and their healthcare teams use to manage the disease.

To learn more about the ongoing challenges of progressive MS, and ways in which the clinical community is working towards tackling this condition, NeurologyLive® sat down with Kathy Zackowski, PhD, OTR. Zackowski, associate vice president of research at the National MS Society, provided insight on the advances in research for progressive MS, the difficulties with developing therapies and conducting clinical trials, and the future outlook of the disease and how its treated.

NeurologyLive®: What are some of the changes and perceptions in progressive MS?

Kathy Zackowski, PhD, OTR: We know now that people with progressive MS tend to have fewer brain lesions with fewer inflammatory cells than people who with relapsing-remitting MS. That may account for the differences in symptoms that we see. Patients with progressive MS also tend to have more spinal cord lesions than brain lesions. There are certain genetic factors associated with the risk of MS, but none of them have been shown to predict the type of MS someone may develop. According to one study, factors like age, and even Epstein-Barr virus, which has gotten a lot of notice, are probably important risk factors for people with progressive MS. In recent years, it's also become increasingly clear how important a general wellness program is for people with progressive MS. It's important not to smoke, to maintain a healthy body weight, to do regular exercise, and to make sure you're not deficient in vitamin D.

What are the complexities with developing therapies for progressive MS?

Progressive MS is hard to study for many reasons. For many people with MS, the treatment is focused on preventing and managing relapses and acute symptoms that are often absent for long stretches of time. There's often no initial relapse that heralds the onset of progressive MS, it's just kind of a gradual appearance of symptoms. This can make progressive MS difficult to identify and to treat. Additionally, patients with progressive MS tend to be older than those with relapsing MS, to the point that he average age of diagnosis of progressive disease is about 10 years later from an initial diagnosis of MS. The reason for this later onset isn't fully understood, but probably reflects neurodegeneration that's accumulating over time.

With the advent of older age, comes the addition of comorbidities like diabetes, and hypertension, which all require their own treatment. The interaction treating those comorbidities with the changes that happen with MS is very hard to parse out. This aging process is something that's gaining a lot of new interest right now in research, and I think will be important. The clinical consequences of progressive MS are varied and cumulative, they can range from mild sensory changes or visual symptoms to profound cognitive and motor impairments. That heterogeneity alone makes it hard to study because when you design a trial, you look for some homogeneity to make your groups similar. It's hard to do when there's such variability.

Lastly, for the research that examines disease-modifying therapies, the weight of evidence comes from studies that predominantly involve people with relapsing-remitting MS. A primary thing we need to do is collect more data with specifically people with progressive MS to allow for more accurate, nuanced picture of these symptoms, and to assure ourselves that there are some differences in how progressive symptoms progress relative to symptoms of people with relapsing remitting MS.

Do you envision the clinical community doing away with the phases of MS?

That's is definitely a hot topic. The way the National MS Society has approached this is to look at kind of a spectrum of disability. Even going from a window of risk—an area where you might not even have obvious symptoms but we know that there's this prodromal stage where there are changes biologically happening—is there a way that we could highlight that time so that people don't even get diagnosed with MS? I feel like instead of talking about it in phases, it might be really advantageous to think of it as a spectrum and highlight or study different periods along that spectrum from this prodromal or subclinical time to the early clinical, diagnosis stage, and even the later stages.

The National MS Society has this roadmap where we're trying to address all those different levels of progression along the spectrum. I don't think there's a right or wrong answer. It's more important that we try to give interventions that occur earlier for people that don't have it (MS) yet, and currently, for people who have MS, to try to repair the myelin, because that's really what is missing in all our treatments. There are no remyelinating medications or interventions that we are clear on at this point.

Transcript edited for clarity.

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