Radical MS chemo

A new Canadian trial published in The Lancet may have found a radical way to halt the acceleration of multiple sclerosis symptoms, but even its authors are wary about its potential dangers.

Dr Harold L Atkins and Dr Mark S Freedman of the University of Ottawa conducted the phase 2 clinical trial on 24 Canadian MS patients whose conditions did not respond to the standard immunosuppressive therapy. After 7.5 years, eight of the surviving 23 patients had a sustained improvement in their disability.

Around two million people worldwide are afflicted with MS, which is one of the most common chronic inflammatory diseases that attacks the central nervous system.

The standard treatment, which the test subjects had not responded to, involves chemotherapy followed by autologous haematopoietic stem cell transplantation (aHSCT). The patients’ own bone marrow is harvested for stem cells that are reintroduced following suppressive chemotherapy in order to ‘reset’ the body’s immune system. This new trial went one step further, completely destroying the body’s immune system with chemotherapy before reintroducing the stem cells, in an effort to reduce the relapse rate and increase long-term disease remission.

The chemotherapy regimen included busulfan, cyclophosphamide and rabbit anti-thymocyte globulin. This form of chemotherapy is known to be very effective at crossing the blood-brain barrier.

After three years, 69.6% of the trial subjects enjoyed multiple sclerosis activity-free survival. One patient died from complications caused by the chemotherapy. Of the surviving 23, there were no relapses, compared with an average of 1.2 relapses per year prior to the treatment. The progressive brain deterioration associated with MS was halted in nine patients while eight showed sustained improvement and six were able to return to work or study.

While the data is promising, Dr Freedman is cautious in his summation.

“The sample size of 24 patients is very small, and no control group was used for comparison with the treatment group. Larger clinical trials will be important to confirm these results. Since this is an aggressive treatment, the potential benefits should be weighed against the risks of serious complications associated with aHSCT.”

He believes future research should determine which MS patients are most likely to benefit from such radical treatment as well as finding ways to reduce associated risks.

In a response to this trial, Dr Jan Dörr, from the NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, said this study is unlikely to change current approaches to MS treatment in the short term.

“Over the longer term [and] in view of the increasing popularity of using early aggressive treatment, there may be support for considering aHSCT less as a rescue therapy and more as a general treatment option, provided the different protocols are harmonised and optimised, the tolerability and safety profile can be further improved, and prognostic markers become available to identify patients at risk of poor prognosis in whom a potentially more hazardous treatment might be justified.”

Image courtesy of Feggy Art under CC BY-NC-ND 2.0