Aggressive Multiple Sclerosis: Is stem cell therapy the answer?

Multiple sclerosis (MS) is often described as unpredictable. For many patients, it follows a relapsing-remitting course with periods of stability. But for a significant subset, MS is aggressive from the outset, causing rapid neurological decline, early disability, and irreversible loss of function. For these patients, conventional therapies aimed at simply slowing progression may not be enough.

MS is an autoimmune disorder in which the immune system attacks myelin, the protective covering of nerve fibres in the brain and spinal cord. Over time, repeated inflammatory attacks lead to axonal damage and permanent neurological deficits. Disease-modifying therapies (DMTs) have undoubtedly improved outcomes, but they largely work by suppressing immune activity rather than correcting the underlying immune dysfunction.

To understand where advanced interventions like autologous hematopoietic stem cell transplantation (AHSCT) fit in, it is important first to recognise what makes MS aggressive.

Clinical experience and global data consistently point to four factors associated with aggressive disease:

1. A high relapse frequency early in the disease, particularly multiple disabling relapses within the first two to three years. Early inflammatory activity is a strong predictor of long-term disability. 

2. Incomplete recovery from relapses: When neurological deficits persist after an attack, it signals ongoing axonal injury rather than reversible inflammation. 

3. Rapid accumulation of disability, often measured by a quick rise in Expanded Disability Status Scale (EDSS) scores, especially within the first five years of diagnosis. 

4. High disease activity on MRI, including a large lesion burden, multiple gadolinium-enhancing lesions, or early involvement of the spinal cord and brainstem.

When these factors are present, MS behaves less like a chronic, manageable illness and more like a relentless neuro-immunological emergency. Delay in effective intervention during this inflammatory window can permanently narrow therapeutic possibilities.

This is where Allogeneic Hematopoietic Stem Cell Therapy (HSCT) represents a transformative shift. 

Unlike standard therapies that continuously dampen immune responses, AHSCT works by rebooting the immune system. The process involves collecting the patient’s own hematopoietic stem cells, followed by immunoablation to eliminate autoreactive immune cells. The stored stem cells are then reinfused, allowing a new immune system to regenerate—one that no longer recognises myelin as a target.

The scientific rationale is clear: MS is driven by immune memory. AHSCT erases that memory and allows immune tolerance to re-establish.

Over the past decade, robust international studies and registry data have demonstrated that, in appropriately selected patients with highly active relapsing-remitting MS, AHSCT can induce long-term, treatment-free remission. Many patients remain relapse-free for years, show no new MRI activity, and experience stabilisation—or even improvement—in neurological disability. Importantly, this remission is achieved without the need for ongoing immunosuppressive therapy.

From a health-economics perspective, the cumulative, year-on-year cost of lifelong high-efficacy disease-modifying therapies often far exceeds that of a single, time-limited AHSCT procedure, which is delivered as a one-time intervention rather than an indefinite financial and therapeutic commitment.

Timing and selection are critical. Outcomes are best in younger patients, those with shorter disease duration, active inflammatory disease, and preserved neurological reserve. Once MS enters a purely progressive phase dominated by neurodegeneration rather than inflammation, the benefits are less predictable. This reinforces the importance of early recognition of aggressive disease and timely referral.

Safety concerns, historically a major deterrent, must be viewed in light of current practice. With refined conditioning regimens, better infection control, and experienced transplant teams, transplant-related mortality has fallen dramatically and is now comparable to many high-efficacy immunotherapies used routinely in neurology. In centres with established expertise, AHSCT has a well-defined and increasingly favourable risk–benefit profile.

Yet, access remains uneven. Many patients are never informed about AHSCT as a therapeutic option, often because it sits at the intersection of neurology and haematology. This gap is not scientific; it is structural. Bridging it requires collaboration, updated guidelines, and informed discussions that prioritise long-term neurological outcomes over therapeutic conservatism.

India has a unique opportunity. With advanced transplant infrastructure, skilled clinicians, and significantly lower costs compared to Western countries, it can emerge as a leader in AHSCT for MS, provided awareness, patient selection, and ethical clinical governance are strengthened.

Aggressive MS does not wait. Every relapse leaves a footprint. AHSCT offers something rare in autoimmune neurology: the possibility of durable remission by addressing disease biology at its root. For carefully selected patients, that can mean halting progression before disability becomes destiny.

As clinicians, our responsibility is not only to slow disease, but to intervene decisively when science allows us to change its course.

The writer is a paediatric haematologist and a bone marrow transplant specialist in New Delhi. He is also a researcher innovating cell therapy solutions.

The opinions expressed in this article are those of the author and do not purport to reflect the opinions or views of THE WEEK.