A Smoldering Process: A New Way of Thinking about Multiple Sclerosis

Published on: October 4, 2023


Emerging science is changing the way researchers think about MS.
Our understanding of the biology of multiple sclerosis is changing. New research sheds light on a potential hidden reason why disability continues to worsen for many patients, despite available therapies.

Multiple sclerosis is as unpredictable as it is complex, with no two people experiencing the symptoms, severity and stages exactly the same. 1,2 That seems almost impossible to imagine, especially given that nearly three million people are living with this disease worldwide – but it’s true.3

There is one constant in MS, and that is a concern for the future. Important questions weigh on the minds of the people diagnosed: What will my future look like? Will this disease one day take away my ability to walk? The ability to be independent? This is a great unmet need in MS – one that scientific innovation must answer.

What Is Going on Inside the Minds of People Living with MS

The unpredictable nature of MS makes it impossible to know the future. This can understandably cause people living with the disease to experience anxiety and fear, thinking about the unknown. Being able to stop disability in its tracks and give people living with MS hope for an independent future is the ultimate goal.
Amanda Montague, ED.M

Amanda Montague, ED.M

Multiple Sclerosis Association of America (MSAA)

Bruna and her husband, Jaime, both living with MS.

Since the first case of MS was identified 150 years ago, researchers have methodically sought to advance the understanding of this complex disease. 4 In the last 20 years, scientific discovery has led to a greater understanding of this neurological disease and the development of dozens of disease-modifying therapies. So why then, does the disease continue to progress?

Is there something more?

A new paradigm is emerging

It has long been thought that MS goes into periods of remission – times when the disease is not active or causing damage.

But new science is challenging that belief.

A look inside the brain

Deep within the brain of those living with MS, researchers have discovered that there is a ‘smoldering process’ underway. Some areas of MS in the brain remain continually active causing destruction – even in times of remission – when there are no relapses.5,6,7 Similar to slow-burning embers, this smoldering process within the brain is thought to drive disability regardless of where a patient is on the spectrum of disease – RRMS, PPMS, PRMS, and SPMS. 5 This emerging science represents an overlooked hidden driver of disability.

Many current therapies work in the areas outside the brain, and for many people with MS these can have little to no impact on the smoldering process inside the brain that may be driving disease disability.5 The smoldering process in MS is emerging as the disease underneath the disease.

This unseen smoldering process in MS slowly causes harmful effects and is believed to be a major driver of disability progression - a critical unmet need in MS. Our research continues to advance the practice of medicine to deliver innovation that helps to improve people's lives.
Tom Snow

Tom Snow

Sanofi's Global Franchise Head, Rare Blood Disorders and Neurology

Evidence shows that the smoldering process starts early on and continues its destructive work, leading to more and more disability. 5,6 If science can target disability at its source—halting the smoldering process in the brain—that could potentially change the course of this debilitating disease forever.

An endless pursuit for answers

For nearly 20 years, Sanofi has been deeply committed to delivering innovative solutions to address the needs of people living with MS. The big challenge now is finding ways to halt disability.

We are leveraging our deep expertise in neurology to break new ground in the study of MS. Our research teams are seeking ways to control the smoldering process within the brain to ultimately halt disability progression and give people with MS hope for a brighter future.


Explore More

Targeting Neuroinflammation in Multiple Sclerosis


  1. National Multiple Sclerosis Society. (2016). Research Directions in MS: Strategies & Progress. New York, NY.
  2. “Multiple Sclerosis (MS): NHS Inform.” NHS Inform | NHS Inform, www.nhsinform.scot/illnesses-and-conditions/brain-nerves-and-spinal-cord/multiple-sclerosis-ms. Accessed 7 Sept. 2023.
  3. “What Is Ms: Multiple Sclerosis.” MS International Federation, 25 Oct. 2021, www.msif.org/about-ms/what-is-ms/.
  4. Martins, Isaura. “Multiple Sclerosis.” Rare Disease Advisor, 20 Dec. 2021, www.rarediseaseadvisor.com/disease-info-pages/multiple-sclerosis/.
  5. Giovannoni G, Popescu V, Wuerfel J, et al. Smouldering multiple sclerosis: the ‘real MS’. Ther Adv Neurol Disord. 2022;15:17562864211066751. doi:10.1177/17562864211066751.
  6. Häusser-Kinzel, Silke, and Martin S. Weber. “The role of B cells and antibodies in multiple sclerosis, neuromyelitis optica, and related disorders.” Frontiers in Immunology, vol. 10, 2019, https://doi.org/10.3389/fimmu.2019.00201.
  7. “Beyond Relapses and Acute Lesions: Smoldering MS Website.” Smoldering Neuroinflammation | Multiple Sclerosis Education Site, www.smolderingms.com/global-en/beyond-ms-relapses. Accessed 7 Sept. 2023.
MAT-GLB-2304621 v1.0 09/2023