Stem-Cell Transplantation Shows Promise in Multiple Sclerosis, but Major Concerns Remain

VBCN - April 2016 Volume 3, No 1

Could stem-cell transplantation prove equally efficacious and more cost-effective than the currently available and expensive drugs for multiple sclerosis (MS)?

Experts weighed in on this topic at ACTRIMS Forum 2016, a recent meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis.

Andrew D. Goodman, MD, Director of the Multiple Sclerosis Center, University of Rochester, NY, began the conversation with the headline from The Economist (January 23, 2016), “Curing Multiple Sclerosis: Stem Cells Are Starting to Prove Their Value as Medical Treatments.”

The topic of stem-cell transplantation, Dr Goodman said, “is much in the public’s mind.”

The article focused on autologous hematopoietic stem-cell transplantation (HSCT), which involves the ablation of the immune system and the reintroduction of stem cells after the immune system is “rebooted.” The therapeutic benefit stems from the immune ablation, not the stem cells.

Other forms of stem-cell transplantation use more “biologically correct” cell-based therapies, according to Dr Goodman. These are derived from mesenchymal stem cells, oligodendrocyte precursor cells, induced pluripotent stem cells, and embryonic stem cells. These approaches may be capable of actually repairing the damaged nervous system, he explained.

Studies are underway with these approaches in relapsing and progressive forms of MS. HSCT is being studied primarily in relapsing MS, whereas progressive MS studies are using the mesenchymal stem cells, oligodendrocyte precursor cells, induced pluripotent stem cells, and embryonic stem cells.

Desperate Patients Susceptible to Hype

Enrollment in stem-cell transplantation clinical trials is much preferred over treatment at clinics that promise to “cure everything,” said Michael K. Racke, MD, Professor of Neurology and Neuroscience, Wexner Medical Center at the Ohio State University, Columbus.

“These are clinics with very slick websites and patient testimonials,” Dr Racke said. “Patients come to me saying they have ‘been approved’ for a transplant and ask if they should go. I say, ‘Approved to pay them $20,000?’”

Other MS experts recounted stories of patients undergoing transplants against their advice, and suffering serious and even fatal complications.

The various cell-based therapeutic strategies under investigation have different risks, benefits, and goals. Some show promise but significant methodological questions need to be answered, according to Dr Goodman.

“The bottom line is that stem-cell transplantation is not yet appropriate for use outside of research settings for the treatment of MS, despite what some of our patients see on the Internet and find in Mexico,” Dr Goodman said.

General Issues Yet to Be Settled

The aim, Dr Goodman said, is for clinical trials to not only assess the safety and efficacy of stem-cell transplantation, but also to answer the following questions:

  • Are the treatments anti-inflammatory, neuroprotective, or reparative?
  • Do the various strategies need to be combined for optimal effect?
  • What is the best route of administration that will target multifocal lesions?
  • Considering disease chronicity, what is the appropriate treatment window?
  • Could transplants paradoxically activate the immune system in a detrimental way?
  • Is the MS nervous system actually hospitable to the concept of introducing cells in an attempt to repair damage?

Studies Completed and Others Planned

The phase 2 HALT-MS clinical trial (Nash RA, et al. JAMA Neurol. 2015;72:159-169) is evaluating whether controlling inflammation earlier in relapsing-remitting MS may lead to prolonged remission and potentially reverse neurologic dysfunction. Results from a 3-year interim analysis showed that after HSCT, nearly 60% of patients were event-free at 5 years, 91% had no progression of disability at 3 years, and the disease in some patients actually improved. This was without additional treatment after transplant. By contrast, the best alternative MS treatments induce much shorter remissions and require long-term use of immunosuppressive drugs that can cause serious side effects.

The article in The Economist suggested that such results “should give drug companies some pause for thought.” Pharmaceutical companies “are already facing criticism for the high prices of MS drugs,” the authors wrote, which can slow the progression of the disease but “cannot do what the stem-cell therapy seems able to, which is to reverse it and improve patients’ quality of life—for example by allowing them to walk again.”

The cost of MS drugs is rising more than 5 times faster than for other prescription drugs, and this does not include the cost of physician visits, magnetic resonance imaging scans, and other monitoring. By contrast, Dr Racke pointed out, HSCT costs approximately $120,000 for potentially a “one off” treatment.

“The government is obviously very interested in the cost of stem-cell transplantation versus the cost for [lifelong] medications,” he said.

Although studies of autologous HSCT have been small and uncontrolled, they have demonstrated “a high level of efficacy, as best we can tell without proper controls, in relapsing patients,” said Dr Goodman.

The best candidates for transplantation seem to be young and still ambulatory, with recent disease onset and relapses despite current treatments.

“But we still need to determine where HSCT fits in, in terms of risk versus benefit, relative to the highly active treatments we now have,” Dr Goodman said, “and how does it stack up in terms of cost-effectiveness?”

More information will come from the phase 3 HALT-MS study, which will randomize patients to receive HSCT or best available comparator. The Bone Marrow Clinical Trials Network has made this study “their number 2 priority,” said Dr Racke.

A phase 1, first-in-human study to be led by the New York State Stem Cell Science program is planned for patients with progressive MS. This study will test transplants involving the glial progenitor cells in 20 patients with secondary progressive MS from 3 New York centers.

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