Shedding a light on progression in MS

Can you remember what you ate for dinner last Tuesday? How about the clothes that you wore on this day two weeks ago? Chances are that you can’t. This is how it can feel to the many people living with chronic diseases who may have months to a year between physician visits when they might be asked to recall changes in their symptoms. As the understanding of lifelong diseases such as multiple sclerosis (MS) grows, we are working to help people and their doctors identify and track how the disease might be progressing.

Cristina Costantino, PhD, MBA, Group Global Medical Science Director at Roche, “We are developing new ways to measure MS, a disease which can hide in the shadows of the brain and central nervous system. If we can accurately measure what is happening in the brain, we can use this information to inform people living with MS about their disease, while working together with neurologists and the MS community to develop new approaches to slow down, or even prevent, disease progression.”

We have been at the forefront of diagnostics and disease monitoring for decades. In the early 1980's, we were one of the first companies to develop an at-home, automated self-monitoring blood glucose meter for people with diabetes. Much like high boold sugar that can seriously damage the body over time if not noticed, underlying MS disease activity can lead to permanent damage in the brain and irreversible disability.

And most people living with MS, their care partners and their physicians will tell you it’s very hard to rely on the recall of symptoms to measure progression. Not only will symptoms be forgotten, but it is difficult to understand the potential importance of symptoms on progression or notice small increases in disability that are accumulating slowly over time.

We are not just committed to advancing science; we believe more is needed to help transform the way MS is measured and managed. One such approach is to make precision monitoring a reality for people with MS and their physicians with MS-specific tests using a smartphone, which most people now carry with them at all times.

“Using their own smartphone, sensor-based measures and patient-reported outcomes, people living with MS can create a personalised record of their status between infrequent clinical visit. This means patients aren’t required to remember and take note of symptoms in between visits to the neurologist. Objective and quantitative measures of changes that may not even be noticed by a patient or their neurologist can provide a more comprehensive picture of disease progression, which may help inform future clinical decisions”, said Costantino.

To fully understand the exciting areas of research that could take the measurement of MS progression to new levels, we first must understand the biology of the disease. In MS, the immune system attacks the insulation around nerve cells in the brain, spinal cord and/or optic nerves, causing inflammation and damage, called lesions. Lesions are visualised with a brain scan called MRI. Conventional MRI measures usually include the total number of overall lesions including active, acute lesions, also known as acute disease activity. It was known for more than 20 years that acute lesions, once formed, may continue to ‘evolve’ and have a chronic life of their own.1 Such lesions are called smouldering plaques and are more frequent in progressive forms of MS.2 So far, smouldering plaques had only been measured in brain tissue after death.

“In recent years, we’ve developed models that are able to automatically measure slowly evolving lesions (SELs) in the brain of MS patients using conventional MRI that could be performed during a regular neurologist visit”, said Costantino. “This is important because SELs may be associated with signs of chronic accumulation of brain tissue damage.”

SELs may provide a marker of chronic disease activity that is not captured by conventional measures of acute MS lesions.

In the past, worsening disability has been shown to be moderately related to the accumulation of acute lesions. However, people with primary progressive MS (PPMS), which is characterised by steady progression of disability, have both acute and chronic lesions.

The most common form of MS is relapsing MS (RMS), characterised by flare-ups of MS symptoms called relapses. In many cases, RMS disease progression is measured by how many relapses a person experiences in a year and/or by the worsening in overall disability which is thought to be related to relapses in this disease form. “Relapses are only part of the picture in terms of progression in RMS”, said Costantino. “Similar to validating SELs as a measure of disease activity, Roche is also validating Progression Independent of Relapse Activity as a new clinical measure of disability progression in RMS.”

Progression Independent of Relapse Activity (PIRA) is a measure of the disability progression that may occur outside of the influence of relapses. Identifying disease progression that is not related to relapse activity is important for people with RMS because this type of progression may cause irreversible decline in mobility and day-to-day quality of life.

We are at the forefront of helping to usher in a new era where physicians are using novel more sensitive quantitative measures and patients are empowered to self-monitor their disease. As we learn more about the biology of MS, it’s becoming clear that a better way to measure disability and monitor the disease is needed to shed light on the entire picture of MS and help the 2.8 million people around the world live their best lives with this disease. It’s possible that in the near future, monitoring MS might be as easy as measuring a person’s blood sugar.

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