World Multiple Sclerosis Day: insights, developments and current regenerative prospects
Multiple Sclerosis (MS), a prevalent disease of the central nervous system (CNS), affects more than 2.8 million people around the world. Established by the MS International Federation, World Multiple Sclerosis Day takes place every year on 30 May, aiming to raise awareness and bring together the global MS community. Here, we highlight key developments in MS research and explore current and emerging regenerative prospects that may improve treatment options for MS patients.
Multiple sclerosis – an unpredictable autoimmune disease
The CNS serves as the body’s control center, responsible for receiving, processing and responding to sensory information, as well as coordinating all bodily functions. Nerve cells within the CNS transmit messages between the brain, spinal cord and the rest of the body. These nerve cells are delicate in nature and are protected by a myelin sheath – a fatty protective layer that helps messages travel quickly along the nerves. Damage to the myelin can slow down or block nerve signals, leading to a variety of symptoms, such as numbness, paralysis and problems with vision and memory. In patients with MS, the body’s immune system mistakenly attacks the myelin sheath, resulting in inflammation and damage. Although the exact cause of MS is unknown, it is considered a complex autoimmune disease, likely influenced by a combination of genetic, autoimmune and environmental factors contributing to its development [1].
Current regenerative cell-based approaches
Decades of research have transformed MS from a poorly understood condition into one with a range of effective treatment options. While current therapies manage symptoms and reduce disease activity, they do not reverse the damage. Regenerative medicine is now offering new possibilities, particularly through cell-based therapies that aim to repair myelin and restore immune balance, providing a more adaptable strategy for addressing both immune dysfunction and tissue repair. Below, we explore the current and emerging regenerative cell therapies for MS, as well as the potential applications of gene therapy in treating this condition.
A targeted therapy
Developed by Abata Therapeutics (MA, USA), ABA-101 is an investigational therapy designed to target chronic inflammation in the central nervous system of MS patients. This approach uses the patient’s regulatory T (Treg) cells, genetically modified to express a T cell receptor that specifically recognizes immunogenic myelin fragments in the CNS. By directing Tregs to these fragments, ABA-101 aims to deliver localized anti-inflammatory effects at the site of the disease, potentially promoting myelin repair and reducing neurodegeneration associated with progressive MS.
After receiving both Investigational New Drug clearance and Fast Track designation in mid-2024, the company announced its intentions to begin a Phase I trial at the end of 2024 (NCT06566261).
Enhanced g-NK cell therapy
In August 2024, the FDA approved Indapta Therapeutics‘ (TX and WA, USA) Investigational New Drug application to study IDP-023, a gamma-delta natural killer (g-NK) cell therapy, in combination with interleukin-2 and ocrelizumab. IDP-023 aims to enhance the immune system’s ability to identify and target autoreactive immune cells that contribute to autoimmune diseases such as MS. The g-NK cells used in this therapy occur naturally in the body and are generated from epigenetic changes that follow exposure to cytomegalovirus, a common and typically harmless virus.
The company is expected to assess IDP-023’s safety, tolerability and biologic activity on autoreactive immune cells in patients with refractory progressive MS in a Phase Ib study (NCT06677710).
The potential of gene therapies
Gene therapies for MS are in the early stages of exploration. Despite this, there have been encouraging findings from experimental mice models of MS showing the potential of gene therapy approaches [2]. For example, researchers at the University of Edinburgh (Scotland) have used CRISPR gene-editing techniques to boost the repair of nerve cells damaged in an MS mouse model [3].
Novel biologics and disease-modifying therapies
The central nervous system is a delicate and complex network, making it especially challenging to treat neurological conditions like MS. While research into cell and gene therapies continues to evolve, several novel biologics and disease-modifying therapies are already available. At the same time, emerging technologies are opening new pathways for advancing regenerative therapies, offering new hope for more effective treatments. Below are some novel biologics and disease-modifying therapies that have caught our eye.
AHSCT – rebuilding the immune system
Autologous hematopoietic stem cell transplantation is a treatment option for relapsing-remitting MS that aims to reset the immune system. This procedure involves collecting stem cells from the bone marrow, administering chemotherapy to eliminate the existing immune cells and then reintroducing the stem cells to rebuild a new immune system. The collected stem cells are infused back into the bloodstream, where they differentiate into new immune cells [4]. This procedure halts or significantly slows MS progression by eliminating the dysfunctional immune cells responsible for attacking the CNS and replacing them with the newly generated immune cells.
Ocrelizumab – selective targeting
Ocrelizumab, a disease-modifying therapy, is approved for various types of MS, including clinically isolated syndrome, relapsing-remitting, progressive and primary progressive MS. Ocrelizumab selectively targets and depletes B cells, reducing the immune system’s attack on myelin and slowing the progression of MS. Studies have shown that ocrelizumab can reduce relapse rates and slow disease progression in early primary progressive MS [5]. Ocrelizumab will be used alongside IDP-023 in a Phase Ib study.
Fractalkine – a promising approach
In 2023, researchers from the University of Alberta (Edmonton, Canada) discovered that fractalkine, a chemokine widely expressed in neurons, promotes myelin repair. The researchers injected fractalkine into mice with chemically induced MS. Their study results demonstrated the potential of fractalkine to enhance the production of new oligodendrocytes (myelin-producing cells) and to stimulate remyelination from reactivated oligodendrocyte precursor cells in the mice’s brains. Additionally, the findings indicated that fractalkine reduced inflammation, which may help minimize damage to myelin and oligodendrocytes. This suggests that fractalkine could be a candidate for therapeutic development.
Looking ahead
Although current treatment options, such as cell-based therapies, biologics and disease-modifying treatments, do not provide a cure for MS, they have significantly improved symptom management and slowed disease progression. These continual scientific advances are steadily expanding the therapeutic landscape, bringing the field closer to more effective, personalized treatments for people living with MS.
Resources for MS