Multiple sclerosis can vary widely in its course of progression. All manifestations of the disease have one thing in common: medications cannot cure the disease. They cannot stop the MS, but at best can slow down its course of progress. In advanced stages, medications as a rule are no longer effective at all.
Using an extreme new form of treatment, researchers have now however succeeded in breaking that pattern: in a study [Paywall] which has now been published in the Lancet, they were able to stop multiple sclerosis in a small group of patients. One subject died however as a result of the radical treatment. The scientists at the University of Ottawa tested a method which is otherwise used in the therapy of forms of leukaemia: they inactivated the immune system of the patient, and then transplanted the patients’ own haematopoietic stem cells, which they had taken previously, back into them.
Suppressing the immune system
As part of the treatment of multiple sclerosis, suppressing the immune system has been a long sought aim. And over that entire time there has been the ever-present problem of keeping side effects under control. The Canadian researchers have now gone even further in their studies: they virtually killed off the entire immune system in the patients undergoing chemotherapy before they transplanted the autologous stem cells into them.
Subjects with poor prognosis
For their experiments taking part in three Canadian hospitals, the researchers chose subjects with MS who had a poor prognosis, and were already affected by the disease. According to the Expanded Disability Status Scale (EDSS) the subjects had a disability level of 3-6 and were between 18 and 50 years old. They first had bone marrow removed and this was preserved as a reserve. The researchers then stimulated the subjects’ haematopoietic stem cells to circulate, in order to obtain them from their blood. Finally they also freed the obtained stem cell transplant from mature immune cells by using CD34-antibodies. The aim was to delete the immunological memory of the patient, such that the immune system would stop destroying myelin. The study subjects were then over several days given the cytostatics busulfan and cyclophosphamide as well as antithymocytic globulin (ATG) from rabbits, an antibody mixture active against immune cells. 48 hours after the last dose of chemotherapy the subjects received their own stem cells as a transplant.
Trial participant died of liver necrosis
For some of the test participants, the treatment was successful. MS came to a standstill for sixteen of them. Within a follow-up period running an average of six and a half years, they had no clinical relapses and no new foci of inflammation in the brain. For some, the impairments involved in and acquired through MS were even partially rebuilt. In seven patients, however, the disease progressed despite treatment.
One subject did not even survive the radical cure. Through a toxic liver injury, his hepatic veins were blocked – a common complication in treatment when using cytostatics. He also suffered a Klebsiella-based sepsis. Two months after treatment, the subject died due to massive liver necrosis. Another subject – in this case also due to liver damage – needed to be treated in intensive care, but nevertheless survived. Many further patients developed partly severe side effects. The “survival rate” sits within the usual limits of bone marrow transplantation, the authors add, and that the risks had been known.
Too hazardous for application
Even though the successful healing of some subjects seems remarkable – as far as clinical application goes, the method is unsuitable. The price which the patients would have to pay for possible treatment success would be too high. They would have to risk their lives – even though the cure would not even be guaranteed. MS, unlike leukaemia, is usually not a fatal disease. One can even find it questionable that such a risky procedure had been employed here at all.
In addition, the progress of MS is difficult to predict. Because it is diversely expressed in every patient, it is also referred to as a disease of 1,000 faces. With their subjects, the scientists merely assumed that the disease would progress significantly within the next 10 years. It is not able to be safely said whether their quality of life would deteriorate so much that employing anticipatory life-threatening measures would be justified. For the patients themselves as well this is something of a somewhat inestimable, profoundly difficult, individual decision. Theoretically, one could indeed investigate efforts to make the approach more compatible. On the other hand the radical nature of the method had indeed led to the successes.
Because of the long follow-up period, the extreme treatment approach, it must be added, dates back to another era: the researchers already began their study in 2000. Meanwhile, conventional MS treatment options have clearly improved. Thus, treatment using a fumaric-esther (approved in Europe since 2004) can halve the frequency of relapses. As MS research makes steady progress, we are allowed to expect further innovation over the coming years.
The future of MS treatment is therefore likely to lie in the development of other, better tolerated drugs.