Multiple sclerosis – the disease of a thousand faces

January 15, 2024

Image: @Jcomp | iStock

Multiple sclerosis (MS) is a disease that impacts the central nervous system, affecting everything we do. For many patients, the main question is: how do I confront this life-changing condition?

In the last 15 years, the therapeutic options for multiple sclerosis (MS) have changed dramatically. Several drugs have been approved that reduce the risk of relapse and show a decrease in disability progression. Disease expert Prof Dr Bart Van Wijmeersch, Professor of Neurology at Hasselt University and the University MS Centre Pelt, discussed with Ann Vanoirbeek, Patient Platform Member of the University MS Centre, about the needs of patients and the development of novel therapies, which will hopefully improve patients’ life quality.

The exact cause of MS is unknown, but we know the immune system attacks the central nervous system (CNS), resulting in damage to the protective nerve fibre coating (myelin) and the formation of lesions through demyelination and disruption of signals to and from the brain. This causes unpredictable symptoms such as numbness, tingling, mood changes, memory problems, pain, fatigue, blindness and even paralysis. For Ann,the worst part is the fatigue, “In my mind, I’m planning things. I think, today I’m going to do this and that, then my body says no. And I must change everything, it’s frustrating. The worst is that each day is different, so it’s a balancing act; sometimes you miss, and you fall.”

Following her diagnosis, Ann was at a loss as her condition worsened rapidly, and four years later, she was in a wheelchair. No one explained to her what the disease entailed or if her body’s reaction to the medication was normal. “18 years ago, when I learned I had MS, the neurologist just gave me a pamphlet for information, and that was it,” commented Ann. “With time, this situation has significantly improved, and now I am well supported at my rehabilitation centre, and there is also the MS Liga, a Belgium association that helps the MS community in this region.”

Relapsing-remitting MS (RR-MS) is the most common form of MS. Up to 85% of people affected receive an initial RR-MS diagnosis. RR-MS is characterised by flare-ups of inflammation in the CNS, which are followed by periods of remission with improved or completely resolved symptoms. (1) The other 10- 15% of patients suffer from what is known as progressive MS, where the neurologic symptoms worsen gradually without relapses or remissions.

The therapeutic landscape of multiple sclerosis

There is currently no cure for MS. Disease modifying therapies (DMTs) in development aim to prevent further tissue damage by blocking the underlying aberrant activity of the immune system. (2)

The greatest challenge for these approaches is that the course of the disease varies greatly between patients, and these symptoms may be temporary or long-lasting. (3) “Some treatments have very severe side effects, which force patients to stop the medication, because it is too aggressive,” explained Ann. “My biggest hope is that, in the future, MS treatment will be personalised, to address each individual’s needs, reducing the side effects.”

Though effective, MS therapies are associated with risks of these side effects and, therefore, require patients to have a risk management plan. This is why current treatment guidelines only recommend high-efficacy DMTs, associated with greater toxicity, to patients with severely active MS where irreversible loss of abilities is evident. Research, however, indicates that the prognosis for MS patients can be significantly improved in the long term through the early use of highly effective therapies.

IMCY-MS-001 trial – an innovative immunotherapy for patients with RR-MS

The MS drug development community is moving very fast to find new and better treatment options for MS patients. “In the last 10-20 years, over 15 DMTs have been approved, and exciting new insights have been discovered to tackle the disease,” highlighted Prof Dr Bart Van Wijmeersch. “However, there is still a long way to go. Many DMTs focus on suppressing the immune system to avoid the formation of new lesions. This type of therapy for young patients can have long-term negative effects. Immunosuppression treatment during 20 to 40 years weakens their bodies, making them more prone to infections and other diseases.”

An interesting approach to tackle MS, is to restore the immune system’s tolerance. That is, correct the part that has a malfunction while leaving the rest intact. “Belgian company Imcyse is taking such an approach,” explained Prof Dr Bart Van Wijmeersch. “With their Imotope technology, they aim to target only the immune cells that are destroying the myelin while leaving the other parts of the immune system functioning – restoring the immune system balance, rather than suppressing it.”

The pathophysiology of MS, with known myelin autoantigens and T cell epitopes which stimulate the immune system to react in unwanted ways, makes this disease a particularly attractive indication for the development of an immunotherapeutic based on Imcyse’s Imotope technology.

Based on a unique mechanism of action, IMCY-0141 is administered as early as possible after diagnosis.
“An interesting aspect of this technology is that, with just a few treatments, early on, you can have long-term control over the disease,” explained Prof Dr Bart Van Wijmeersch. “It may potentially switch-off the autoimmune process and limit the corresponding myelin destruction.”

Before launching any efficacy studies, the safety of IMCY-0141 in MS patients is being evaluated in a phase 1, open-label, dose escalation clinical trial to evaluate the safety of three IMCY-0141 doses. Preliminary data has, to date, found no safety concerns; the final outcome reviewing the effects of the highest dose is expected soon. This study has recently completed recruitment, and the results will help define a phase 2 study, which will aim to assess the immune response of the patients. (4)

What will the future bring?

With no time to lose, many clinical trials are taking place to improve the therapeutic options for MS patients. Even though some of them are not going to be available fast enough, there is hope that new drugs working in new ways will significantly benefit MS patients.

“In the short term, what we need is to have highly efficacious drugs that can be used very early on to stop the disease, of course, with good safety profiles,” said Prof Dr Bart Van Wijmeersch. “Also, therapies that can help patients with advanced MS are in great need. Especially for those suffering from progressive MS. In this area, new targets are being identified that could potentially improve the prognosis of the disease.”

For both Prof Dr Bart Van Wijmeersch and Ann, the most significant achievement would be to stop the disease and repair old myelin lesions, offering a cure for this devastating disease.