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Session 3: Advances in hot topics
Author/ Session/ 20 September 2025
PCD 2025 “hot topics” are defined as the topics that matter most to people living with MS and related conditions – from everyday challenges such as cognition, to breakthroughs in biomarkers, genetics, and artificial intelligence.
Panellists
- Ali Manouchehrinia, Researcher, University of Manitoba, Canada
- Daniel Ontaneda, Neurologist, Cleveland Clinic, USA
- Jeannette Lechner-Scott, Researcher, University of Newcastle, Australia
- Liliana Patrucco, Neurologist, Centro de Esclerosis Múltiple de Buenos Aires (CEMBA), Argentina
- Mitzi Joi Williams, Neurologist, Joi Life Wellness Group, USA
- Olga Ciccarelli, Researcher, ECTRIMS Vice-President, UK
- Xavier Montalban, Neurologist, Multiple Sclerosis Centre of Catalonia (Cemcat), Spain
Cognition
The majority of people living with MS and related conditions will experience cognitive issues at some point in their patient journey. Cognitive problems include difficulty paying attention, planning, switching between tasks, finding the right word when speaking and memory problems. This can have a huge impact on a person’s employment, social life, and everyday activities.
At this year’s ECTRIMS congress, cognition was the focus of the keynote lecture.
Key learnings:
- Researchers used to think that cognitive issues mainly affected people who had had MS for a long time. Now they know that these issues can arise from the earliest stages of disease.
- Other common symptoms of MS, such as fatigue and low mood, can make cognitive issues worse.
Brain-healthy activities, such as improving sleep quality, eating a balanced diet, engaging in physical activity and quitting smoking, can help ease cognitive issues.
Olga Ciccarelli: “Everyone’s brain ages. But that process is probably faster in people with MS. We have to look after our brain as much as we can, and there are things people can do to maintain healthy ageing.”
Biomarkers
Biomarkers are measurable signals of a normal or abnormal process, or of a particular condition. Doctors may look for biomarkers in the blood, the spinal fluid, or on imaging scans, and use them to understand what is going on inside the body.
There has been a lot of advances in biomarkers in recent years, making them one of the most exciting areas of current research.
Key learnings:
- Biomarkers may be able to help doctors predict who will experience slow worsening of their disease, and measure some of the silent symptoms that people experience. That includes things like cognition issues, fatigue, numbness and tingling.
- One study presented at ECTRIMS 2025 found a link between a combination of 13 different proteins in the cerebrospinal fluid (CSF) and progression independent of relapse (PIRA). This information may help researchers build tools that can spot people at risk of PIRA, or even guide the development of new treatments.
- Another study found that glial fibrillary acidic protein (GFAP) may be able to tell doctors about disease progression. People with high levels of GFAP in their blood appear to have a slow worsening of MS over time, it said. This finding could lead to new ways to prevent or treat progression.
Mitzi Joi Williams: “Advances in biomarkers will help us better understand what is going on later on in the disease. In earlier disease, MRI is our best measure to determine if people are worsening, because we can see new lesions and inflammation. When we get into the more progressive phase of the disease, there are more subtle things that may be occurring on MRI that we cannot measure in the clinic. Blood tests are really helpful because they can, potentially, help us to measure disease activity and progression in a different way.”
Smouldering MS
Smouldering MS, or MS that gets worse but not because of relapses, was a main focus of ECTRIMS 2025. Smouldering MS describes chronic, or ongoing, inflammation in the central nervous system (CNS).
It is something that researchers are learning more about all the time. They are finding new ways to measure and detect it, and even ways to treat it.
Key learnings:
- Not everyone with MS will experience smouldering MS.
- At ECTRIMS 2025, researchers heard about possible new treatments for smouldering MS. They include Bruton’s tyrosine kinase (BTK) inhibitors and CAR-T cells. These treatments may be able to cross the blood-brain barrier to reach the inflammation in the CNS.
- Panellists highlighted a phase III clinical trial of a BTK in people with secondary progressive MS with no relapses. It found the drug could delay the progression of disability by 31%, compared to placebo, or a dummy treatment.
Xavier Montalban said of the BTK clinical trial: “If this drug is approved, it will add a new option to our armamentarium,” he said. “There are two or three other BTKs coming, perhaps even more specific, probably efficacious, and perhaps with fewer side effects.”
Artificial intelligence
Artificial intelligence (AI) is playing a key role in the research world, helping investigators to gather and understand more data than ever before. It can combine multiple types of data, such as MRI, genetics, biomarkers, and clinical information, spotting patterns in a way the human brain cannot.
Key learnings:
- AI is being used across the healthcare system. AI-powered transcription tools, for example, can record doctor–patient conversations and generate clinical notes. Some healthcare professionals feel this helps them concentrate on the person they are talking to
- Researchers are using AI to screen thousands of compounds or molecules at a time. It means they can find the most promising, least toxic drug candidates in a fraction of the time.
- In research, the more people involved in studies, the more reliable the results. AI can work with datasets of tens of thousands of people. This makes predictions more accurate. It will be particularly important to ensure that AI systems are trained across a diverse range of participants. Diversity in MS clinical trials has been a hot topic of conversation and this will continue to be important as the role of AI increases in these studies.
- In other diseases, including Alzheimer’s, researchers are using AI to speed up clinical trials. One way they are doing this is by using the technology to find people who are most likely to respond to the treatment being studied.
Genetics
One of the biggest questions people often have is why some people develop MS while others do not. Or why the condition progresses more quickly in some people than in others.
Part of the answer lies in genetics. While no single MS gene exists, researchers have identified hundreds of genetic variations that can slightly increase the risk, and are starting to identify genes that increase the risk of accelerated disease progression.
Ali Manouchehrinia: “It is really important for MS genetics research to bring in a mixture of nations. We need, for example, to bring in African Americans who have been underrepresented in MS genetics. We are hopeful that all this information will help us understand the disease better.”
Key learnings:
- People with certain genes may be predisposed, or more likely in given circumstances, to develop an autoimmune disease. MS is just one example of an autoimmune disease.
- Genetics alone cannot fully predict MS. Lifestyle and environmental factors, such as smoking, low vitamin D, and viral infections such as the Epstein-Barr virus (EBV), also play a role. Researchers call the area where genetics and environmental factors meet epigenetics. Epigenetics may be more predictive than genes alone.
- At ECTRIMS 2025, researchers shared information on new AI-based models that combined genetic information with clinical and biological markers. The aim was to better understand how people develop and experience MS. This could eventually lead to more personalised treatments.
- Many thousands of study participants are needed to move this field of research to the next step. The International MS Genetics Consortium has been incredibly successful at enabling global collaborations, using data from people living MS around the world, to help start to answer these questions.
Jeannette Lechner-Scott: “Epigenetics is much better in predicting your risk of MS than genes alone. It is a combination of your genetic predisposition, your lifestyle factors, and what you experience during your lifetime that makes up that risk.”
Infections and vaccinations
Infections, especially EBV, are strongly linked to the risk of developing MS. At the same time, vaccinations play a crucial role in managing MS safely, particularly when patients are starting treatments that affect the immune system.
Key learnings
- Several trials are underway to develop a vaccine to EBV. Researchers hope that preventing EBV infection could reduce the number of people who develop MS in the future.
- It is important for people with MS to have all recommended vaccines before they begin DMTs. This is because a person’s response to a vaccine may be weaker after treatment begins, as DMTs supress the immune system and can make people vulnerable to infections.
- There is strong evidence to show that vaccination is safe and effective in people with MS.
Liliana Patrucco: “The majority of infections related to the use of high-efficacy therapy are mild or moderate, and we can deal with them perfectly well. The treatments are safe, and vaccines are safe. We need to combine them to achieve good control of the disease activity, and to maintain a good state of well-being.”