Multiple sclerosis research is entering an important new chapter, and Dr. Jiwon Oh is helping lead the field toward it.
As Medical Director of the BARLO MS Centre and the Waugh Family Chair in Multiple Sclerosis at St. Michael’s Hospital, Dr. Oh is at the forefront of international efforts to understand BTK inhibitors, a new class of MS treatments that may help address one of patients’ greatest unmet needs: slowing disease progression, especially for people whose disease continues to worsen even when they are no longer having obvious relapses.
Today, many MS treatments are effective at reducing relapses. But for too many people, MS can still progress quietly in the brain and spinal cord, gradually affecting mobility, independence, cognition, and quality of life. This slow, hidden progression remains one of the hardest challenges in MS treatment.
BTK inhibitors are exciting because some may be able to reach immune activity inside the central nervous system—the brain and spinal cord—where progressive MS is believed to take hold. By targeting immune cells involved in MS, including B cells and microglia, these treatments may help researchers address disease processes that have been difficult to reach with existing therapies.
As lead author of both a major recent review in The Lancet Neurology and a 2025 study in The New England Journal of Medicine examining the BTK inhibitor tolebrutinib in people with relapsing MS, Dr. Oh has helped advance international understanding of this emerging class of treatment. Together with international, Dr. Oh is examining the latest evidence—including what clinical trials have shown so far, why results may differ across drugs and patient groups, and what questions remain before BTK inhibitors can become part of everyday MS care.
The findings are promising but still evolving. And with support from BARLO’s extraordinary community of donors, Dr. Oh is helping answer one of the most urgent questions in MS care: how do we protect people from relapses and from the slow progression that can change the course of their lives?
In a Q&A, Dr. Oh shares her thoughts about what her latest findings mean about the future of MS treatments and what keeps her motivated in her work.
What led you to the field of neurology and MS in the first place?
From early on in medical school, I was drawn to the study of the brain and nervous system because it is such a complex and intricate organ. It remains a bit of a mystery.
I ended up being drawn to the field of MS for a few reasons. It is a chronic disease that affects many young people in Canada and around the world, and there is a major unmet need to figure out how to treat MS more effectively. It is also a very dynamic field, with a lot of scientific activity and constant change and improvement. This greatly appealed to the academic and scientific side of me, while the potential for hope greatly appealed to the clinician side of me.
Finally, because my mom had been affected by vasculitis that led to a stroke, leaving her with significant neurological disability when I was a child, MS was a field that hit close to home. I grew up understanding the struggles my mom experienced as someone affected by a chronic inflammatory neurological disorder, and I felt I could make the greatest difference clinically and scientifically in such a field.
How does your work as both a clinician and scientist shape your research, and how does seeing patients with progressive MS influence your sense of urgency?
I love being both a clinician and scientist and would never give up either aspect of my job, as each feeds into the other and makes me better at both.
Being a clinician keeps me close to the needs of my patients and helps me understand the most important questions and needs for people living with MS. It also constantly allows me to identify new questions that can be answered using science. Seeing the struggles of patients who experience ongoing neurological progression makes me realize that this is truly the greatest unmet need in MS.
Being a scientist allows me to be original and creative in my work and keeps me close to cutting-edge developments and the latest evidence that helps me care most meaningfully for my patients.
What does disability progression look like in daily life, and why has progressive MS been so difficult to treat?
Disability progression that is independent of relapsing activity is extremely common in people with MS, regardless of disease type or stage. This is something that even people living with early relapsing MS report, and it can manifest in many different ways.
For some people, it may increase fatigue. For others, it can increase difficulties with memory, concentration, or word-finding. It can also mean increasing limitations with physical functioning. We do not yet have a complete understanding of all the mechanisms underlying progression in MS, which is one major reason it has been so difficult to treat.
It is also very difficult to measure subtle progression in people with MS. In contrast, it is much easier to measure relapses, and we have MRI measures that can reflect relapsing disease biology. We do not have similar MRI measures for progression in MS.
What drew you to studying BTK inhibitors, and why are they being investigated in MS?
One of the biggest gaps in MS treatment is finding a therapy that can slow the disease from getting worse even when a person is not having obvious relapses.
BTK inhibitors are promising because they are small enough to enter the brain and spinal cord. Once there, they can affect immune cells involved in MS both inside and outside the central nervous system.
BTK is a protein that helps certain immune cells, especially B cells, develop and function. Scientists first understood its importance after discovering that changes in the BTK gene cause a rare inherited immune disorder. Drugs that block BTK were later developed to treat cancers involving abnormal B cells and have been used for this purpose for many years.
Because B cells also contribute to autoimmune diseases, researchers are now studying BTK inhibitors in MS and several other conditions.
In MS, these drugs may be particularly useful because they influence both B cells and microglia—immune cells in the brain and spinal cord that may contribute to ongoing inflammation and disease progression. As a result, there has been a flurry of BTK inhibitor development in MS over the past decade, resulting in the simultaneous evaluation of six BTK inhibitors in phase 2 and phase 3 clinical trials.
Why is the blood-brain barrier such an important obstacle, and what does it mean if a treatment can reach immune activity within the central nervous system?
The vast majority of our existing MS therapies cannot easily cross the blood-brain barrier and get into the central nervous system.
The central nervous system is where the cells and cellular processes that mediate progressive disease occur, so it is essential that a treatment designed to address progressive disease biology can cross the blood-brain barrier.
Immune activity mediated by B cells and microglia in the central nervous system is known to be a major driver of progressive disease biology.
Why is this considered a potential new era for progressive MS, and what could these findings mean for patients who currently have few treatment options?
BTK inhibitors are small molecules that modulate both B cells and microglia. These are cells in the central nervous system that we know play a dominant role in mediating progressive disease biology. They can also get into the central nervous system easily.
Based on this, as well as the results observed in clinical trials of BTK inhibitors in both progressive and relapsing MS, it seems very likely that BTK inhibitors are addressing progressive disease biology that our current therapies are not adequately targeting. This is why it is a new era for the treatment of progressive MS.
People with MS who experience slow progression that is independent of relapsing disease do not currently have any effective treatment options.
In addition, data from fenebrutinib suggest that it is highly effective against relapsing disease activity, suggesting that it may be a new oral treatment that is highly effective against relapsing disease activity.
What message would you share with people living with progressive MS today?
There is hope!
And what gives you that hope right now?
Data from BTK inhibitors make me hopeful that we are entering a new era of treatments in MS that can finally address some of the mechanisms underlying progression that is independent of relapsing activity. In addition, there are many experimental therapies in the early stages of development that offer hope for new treatments for progression in MS.
How has support from BARLO’s donor community helped advance your work and research at BARLO?
Donor support has been transformative for my career. It has also been crucial in establishing the BARLO MS Centre as the Centre of Excellence in clinical care, research, innovation, and education that it is today. None of this would have been possible without our donor community.
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