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First Successful Therapy for Multiple Sclerosis: Stem Cells Lead the Way



Review of “Association of Non-myeloablative Hematopoietic Stem Cell Transplantation with Neurological Disability in Patients With Relapsing-Remitting Multiple Sclerosis” from JAMA by Stuart P. Atkinson

Multiple sclerosis (MS) is a debilitating disease of the nervous system, associated with inflammation and damage of the myelin sheaths which protect nerve cells. Most patients require assistance to walk at 15 years or are unable to walk by 25 years, and at this time, no therapy exists which can reverse the neurological effects or improve quality of life. In a widely reported study published in JAMA, researchers have now assessed the effectiveness of non-myeloablative hematopoietic stem cell transplantation (HSCT), used to reset and not suppress the immune system [1-3], encompassing a previous trial which displayed some improvement in neurological disability and quality of life [4]. They now show that HSCT is associated with an improvement in neurological disability and other clinical outcomes, representing the first successful treatment for MS [5].

The study analyzed 145 patients who received HSCT, with a median age of 37 and followed up for a median of 2 years. The Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis, and represented the primary endpoint of the study. Encouragingly, EDSS scores improved significantly in 41 patients at 2 years and 23 patients at 4 years. Encouragement positive signs were also observed in the multiple secondary end points of the trial:

  • Four-year Kaplan- Meier estimated relapse-free survival was 80% and progression-free survival was 87%. 
  • Neurologic Rating Scale (NRS), developed for the clinical assessment of patients with MS, improved significantly at 2 and 4 years.
  • Multiple Sclerosis Functional Composite (MSFC) score, a three-part, standardized, quantitative, assessment instrument for use in clinical trials of MS, improved at 2 and 4 years (includes improved ambulation, arm function and cognitive function)
  • Total quality-of-life scores significantly improved at a median follow-up of 2 years.
  • Significant decrease in MS-associated brain lesion volume at the last post-transplant assessment.
  • Significant improvements in both physical and mental health noted from patients SF-36 multi-purpose, short-form health survey. 

Post Hoc Analysis (looking at the data after the experiment has concluded for patterns that were not specified a priori) found that sex, age, baseline EDSS score, and prior number of immune drugs were not significantly associated with post-transplant EDSS scores, although EDSS scores did not significantly increase in those patients with secondary MS (as opposed to relapsing remitting MS), a disease duration of disease of more than 10 years, and those who had suffered sustained fever during HSCT. 

The authors note that this is the first treatment to improve EDSS score in relapsing-remitting MS, linking non-myeloablative HSCT with improvement in neurological and other clinical outcomes. This is in comparison to various other completed clinical trials (AFFIRM, SENTINEL, TOP, CARE-MS I, and CARE-MS II) which showed no improvements associated with any treatment type. The authors do note several limitations to their study, including study completion at only one institute, lack of long-term follow-up in a substantial proportion of patients, and as the fact that the trial was an observational cohort without a control group, meaning that definitive conclusions will require a randomized trial, which this excellent study provides the basis for.


  1. Burt RK, Loh Y, Pearce W, et al. Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases. JAMA 2008;299:925-936.
  2. Abrahamsson SV, Angelini DF, Dubinsky AN, et al. Non-myeloablative autologous haematopoietic stem cell transplantation expands regulatory cells and depletes IL-17 producing mucosal-associated invariant T cells in multiple sclerosis. Brain : a journal of neurology 2013;136:2888-2903.
  3. Muraro PA, Douek DC, Packer A, et al. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. The Journal of experimental medicine 2005;201:805-816.
  4. Burt RK, Loh Y, Cohen B, et al. Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. The Lancet. Neurology 2009;8:244-253.
  5. Burt RK, Balabanov R, Han X, et al. Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsing-remitting multiple sclerosis. JAMA 2015;313:275-284.