Shedding Light on 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 doctor visits whe n they might be asked to recall changes in their symptoms. As the understanding of lifelong diseases such as multiple sclerosis (MS) grows, Genentech is working to help people and their doctors identify and track how the disease might be progressing.

Shibeshih Belachew, M.D., Ph.D., senior international medical director, with Roche – Genentech’s parent company, is part of a global team working to develop new ways to measure MS. “We hope to shed light on a disease that, for many people, lives in the dark. The challenge we face is finding a way to see exactly what’s going on inside the brain and central nervous system, measure those changes accurately, and then use that information to slow, and hopefully prevent disease progression in people with MS.”

Roche has been at the forefront of diagnostics and disease monitoring for decades. In the early 1980’s, it was one of the first companies to develop an at-home, automated self-monitoring blood glucose meter for people with diabetes. Much like high blood 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.

We may soon be able to use sensors to go beyond the visible, beyond what the neurologist may see and beyond what the patient could consciously experience.

- Shibeshih Belachew, M.D., Ph.D.

And most people living with MS, their support partners and their doctors will tell you it’s very hard to rely on recalling 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.

At Genentech, 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 doctors with MS-specific, active neurological tests and passive monitoring using a hand-held smartphone.

“Having something available that can objectively and quantitatively measure daily disease status without requiring people to remember symptoms is important for successful MS monitoring,” said Belachew. “We may soon be able to use sensors to go beyond the visible, beyond what the neurologist may see and beyond what the patient could consciously experience. Disease progression that could have otherwise gone unnoticed may be identified and managed to increase the likelihood of preventing future disability.”

To fully understand the exciting areas of research that are taking 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 visualized 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.

SELs are an emerging marker of chronic disease activity, which only recently have become identifiable through conventional MRI.

“Recently, we’ve been able to develop a method to automatically measure slowly evolving lesions (SELs) in the brain of MS patients with a new algorithm using conventional MRI that could be performed at a patient’s visit to their neurologist,” said Belachew. “SELs may correspond to smouldering plaques and could 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 characterized by steady progression of disability, have both acute and chronic lesions. “We are working to determine if the unrelenting disability progression mostly seen in PPMS is related to SELs and if specific treatments may reduce this type of disease activity,” said Belachew.

To understand the full picture of progression in RMS, we have to look beyond relapses.

- Shibeshih Belachew, M.D., Ph.D.

The most common form of MS is relapsing MS (RMS), characterized 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.

“To understand the full picture of progression in RMS, we have to look beyond relapses,” said Belachew. “Just like SELs may measure underlying disease activity beyond acute lesions, Genentech is validating a new clinical measure of disability progression in RMS outside of relapses called Progression Independent of Relapse Activity.”

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.

PIRA is a measure of disability progression that may occur outside the influence of acute relapses.

“People living with RMS might immediately notice the effects of a relapse, but are less likely to perceive the gradual progression of disability until it accumulates to a point where it affects daily living,” said Belachew. “Right now, outside of clinical trials, we need a more reliable way to identify and better manage this type of disability progression – before the loss of abilities are irreversible. We are excited to be working on this challenge.”

Genentech is at the forefront of helping to usher in a new era where doctors are using novel, more sensitive 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 2.3 million people around the world live their best lives with this disease.

1. Sethi V et al Mult Scler. 2017 Mar;23(3):464-472.

2. Frischer JM. Clinical and Pathological Insights into the Dynamic Nature of the White Matter Multiple Sclerosis Plaque. Ann Neurol. 2015 November;78(5):710–721.