A research study published June 2016 in the prestigious journal, The Lancet, details a very risky but effective cure for patients with aggressive multiple sclerosis (1). In multiple sclerosis (MS), the immune system attacks its own insulating material called myelin which usually covers nerve cells in the brain and spinal cord. There is currently no cure, but symptoms may be managed through the use of medications that manage inflammation and inhibit the immune system to dampen further demyelinating damage. Symptoms vary among individuals but can include numbness, weakness in the limbs, loss of balance, fatigue, and blurred vision. More severe cases can involve paralysis. The medical procedure described in The Lancet relies on the harvesting of a patient’s own hematopoietic stem cells to be used as grafts after almost completely destroying the patient’s existing immune system. This autologous hematopoietic stem-cell harvest, which selects for CD34+ progenitor cells, is taken from the patient after stimulation (mobilization) to increase the numbers of circulating myeloid stem cells (2). This is done with the chemotherapy drug, cyclophosphamide, and filgrastim, a granulocyte colony-stimulating factor analog which promotes the rapid increase and differentiation of a type of white blood cell called granulocytes. A cure to MS is possible through the ablation of the current faulty immune system of MS, and the subsequent replacement with hematopoietic stem cells that can then become healthy immune blood cells.
The study began in 2000, and the paper describes Phase 2 of the study at three hospitals in Canada. Twenty-four patients participated, and one has died during the study due to liver complications. The treatment is initially quite toxic, and strong chemotherapy drugs are given to destroy the immune cells. After immune cells are rendered null through the use of busulfan, cyclophosphamide, and rabbit anti-thymocyte globulin, the patient is left vulnerable to infection. The chemotherapy is toxic to sperm or eggs, and women enter early menopause. Hair and fingernails fall off. Yet, MS patients desperately searching for a cure have chosen this option and experienced not only a cessation of symptoms, but also some recovery from previous MS-induced damage. Patients were followed up for up to thirteen years after autologous hematopoietic stem-cell transplantation, and even though they were not on any medications, they were found to be free of relapses and without any new brain lesions in MRI scans.
Interestingly, this process of “resetting” the immune system was found to be effective for MS quite accidentally. Initially, people with both leukaemia and MS were being treated for leukaemia, a cancer of the white blood immune cells. This cancer starts in the bone marrow, so autologous blood stem cells from the bone marrow are first collected and rid of any cancerous cells. The cells are then reintroduced into the body as a graft to elicit new, healthy immune cells after the existing, cancer-ridden immune system is destroyed by toxic chemotherapy. The results were found to be effective not only for leukaemia, but for MS as well. It is hoped that a similar approach can be used to cure other autoimmune diseases such as Crohn’s disease, scleroderma, and lupus. The risk associated with deleting a person’s entire immune system is great, but by adjusting the balance between toxicity and maximal therapeutic results, a safer medical intervention can be found. Larger trials can be conducted to determine the best dosage and effectiveness so that hopes can be high for people suffering from MS and other debilitating autoimmune diseases.