Multiple Sclerosis (MS) is a debilitating autoimmune disease in which the immune system attacks elements of the central nervous system. There are different types of MS, but more progressive cases can leave patients unable to walk and may require rather extreme immunosuppressive treatments that can predispose a patient to illness and cancer.
However, a new study that was published in the journal Neurology has shown that stem cell transplantation could be a more effective therapy in severe cases of multiple sclerosis (MS) than the drug mitoxantrone.
Mitoxanthone is a “type II topoisomerase inhibitor” that disrupts DNA synthesis and DNA repair by inserting between the bases in DNA. Mitoxanthone can cause nausea, vomiting, hair loss, heart damage, and suppression of the immune system. Some side effects may have delayed onset. Heart damage (cardiomyopathy) is a particularly concerning effect with this drug, since it is irreversible. Therefore, because of the risk of cardiomyopathy, mitoxantrone carries a limit on the cumulative lifetime dose, which is based on the body surface area of patients.
Because MS is an immune-mediated disorder, and because immune cells are made by stem cells in the bone marrow, bone marrow transplants (hematopoietic stem cell transplantation), which are routinely used in the treatment of leukemia and lymphoma, are being considered as a treatment for MS.
A clinical trial conducted by Giovanni Mancardi from the University of Genova, Italy designed a randomized phase II clinical trial study that included 21 MS patients, whose average age was 36 and whose disability due to the disease had worsened in the previous year despite the fact that the patients were under conventional medication treatment. The average disability level of the participants was represented by the need of a crutch or cane to walk. The goal of the study was to determine the efficacy of intense immunosuppression followed by either a bone marrow transplant with the patient’s own bone marrow, or mitoxantrone (MTX) in MS disease activity.
All participants in this clinical trial received immune-suppressive medication. MTX was given to 12 of the patients while the remaining 9 received hematopoietic stem cells harvested from their own bone marrow. After treatment with MTX, the stem cells were intravenously reintroduced into their donors and the stem cells migrated back to the bone marrow where they generated new immune cells. All participants were followed-up for a period of up to four years after their treatment.
“This process appears to reset the immune system,” said the lead study author Dr. Giovanni Mancardi. “With these results, we can speculate that stem cell treatment may profoundly affect the course of the disease.”
Mancardi and his team found that treatment of MS patients with robust immunosuppression followed by stem cell treatment resulted in a significantly higher decrease in disease progression in comparison with MTX treatment alone. MS patients under stem cell treatment reduced the number of new areas of brain damage (T2 lesions) by 79% compared to patients under MTX treatment. Another type of lesion seen in MS patients – gadolinium-enhancing lesions – were not detected in patients under stem cell treatment during the study, whereas 56% of patients receiving MTX exhibited at least one new gadolinium-enhancing lesion.
Mancardi and his team concluded that an intense immunosuppression followed by autologous hematopoietic stem cell transplantation is more efficient than MTX to reduce MS activity in severe cases.
“More research is needed with larger numbers of patients who are randomized to receive either the stem cell transplant or an approved therapy, but it’s very exciting to see that this treatment may be so superior to a current treatment for people with severe MS that is not responding well to standard treatments,” concluded study author Dr. Mancardi.