A bone marrow or blood stem cell transplant has been an effective but risky way to treat multiple sclerosis (MS) for a few patients, and now researchers know more about why the treatment can reduce autoimmunity and regenerate the immune system. Knowing more about the mechanisms underlying the approach could bring it to more patients in more countries. The findings have been reported in Science Translational Medicine.
In MS, the immune system erroneously attacks the myelin sheath, an insulation that coats many nerve cells. Because neurons in the central nervous system are affected, this disorder can cause debilitating symptoms including fatigue, pain, and paralysis.
Eighty percent of MS patients are free of disease over the long-term, or even forever, after they receive an autologous hematopoietic stem cell transplant, noted senior study author and recently retired Professor Roland Martin of the University of Zurich.
Younger people with aggressive forms of MS benefit the most from the transplant treatment. The University Hospital Zurich (USZ) clinic is the only one in Switzerland that can perform this treatment, which has been found to be highly effective and has a low mortality rate.
The treatment is not without risk. First, bone marrow, containing stem cells that generate immune cells for the blood, is harvested from a patient. Then the immune system must be totally destroyed with various chemotherapy drugs, ablating the cells in the bone marrow that produce immune cells, including a type of T cell that attacks the central nervous system in MS. Patients then get their blood stem cells put back in, which can be used by the body to regenerate the immune system, without the autoreactive cells that attack the myelin sheath of neurons.
This study has answered questions about the process, such as whether any immune cells remained after the chemotherapy, and if autoimmune cells did not return.
The researchers examined 27 MS patients who had undergone the procedure, before, during, and up to two years afterwards. Memory T cells that recall past infections immediately returned after the transplant, but they had actually survived the chemotherapy. They are not thought to pose a risk of MS recurrence.
"They are pre-damaged due to the chemotherapy and therefore no longer able to trigger an autoimmune reaction," explained Martin.
Various types of immune cells were gradually remade in the months after the procedure, with the thymus playing a central role.
"Adults have very little functioning tissue left in the thymus, but after a transplant, the organ appears to resume its function and ensures the creation of a completely new repertoire of T cells which evidently do not trigger MS or cause it to return," said Martin.
More Phase III trials, which are very expensive, will not probably be needed to bring this treatment to more countries.
"Phase III studies cost several hundred million euros, and pharmaceutical companies are only willing to conduct them if they will make money afterward," said Martin. Stem cell therapy does not utilize drugs that are patent-protected, so they don't lead to profits later.
Some MS patients have gone to Israel or Mexico to get this treatment. Hopefully, more patients will be able to access this potential cure soon.