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Stem Cells in Focus

Hematopoietic Stem Cells: a New Transplant Paradigm for Multiple Sclerosis?

Expert Contributor: Harold L. Atkins, MD

For years now, bone marrow transplants have been used to treat patients with leukemia and other blood disorders. The hematopoietic (blood-forming) stem cells present in bone marrow can restore a patient’s blood system after it has been devastated by chemotherapy or radiation. This same approach is now being tested in clinical trials for people with multiple sclerosis (MS) and other autoimmune diseases in the hope that providing brand new blood cells will reset the immune system to a healthy state.

Dr. Harry Atkins, from the Ottawa Hospital Research Institute (OHRI), is one of the scientists working in this field. Previously, he had been exploring ways to manipulate the immune system in leukemia patients to be able to give them highly mismatched donor stem cell transplants, and one of his colleagues wondered if the approach might also work for autoimmune diseases. At about the same time, he met Dr. Mark Freedman, also at the OHRI, and together they discussed which autoimmune disease to focus on. They chose MS. 

There is still no cure for MS. When the body’s own immune system attacks parts of the central nervous system (brain and spinal cord), two crucial elements are damaged: myelin and nerve axons. Myelin is layered in a protective sheath made by specialized brain cells, the  oligodendrocytes (Oligo) that wind around nerves much the same way that insulation winds around electrical wires (as shown in the figure). Without myelin, nerve impulses are too slow to be useful. Axons are the long nerve extensions that transmit electrical impulses from one nerve cell to the next. During MS, the pockets of damage (lesions) to myelin and nerve axons inevitably lead to slower and slower nerve conduction, short circuits, and irreversible nerve damage. The resulting disabilities may be fleeting at first, but repeated attacks render the central nervous system incapable of long-lasting repair, and individuals are left with permanent nerve damage and chronic disabilities.

But is there any reason to think that hematopoietic stem cell transplants (HSCT) could ‘reset’ the immune system in MS? Keep in mind that these are the stem cells that power the blood and immune systems, churning out billions of blood cells every day.

Dr. Atkins explains some of the main pillars of scientific evidence. Scientists first tested the approach in animals with an MS-like disease and showed that radiation or chemotherapy followed by a bone marrow stem cell transplant could help to control the immune system. At the same time, there were reports that patients who had received bone marrow transplants for leukemia, who also had MS, had some improvements in their MS. And when clinicians started to do autologous (using the patient’s own cells) bone marrow transplants in people with other autoimmune diseases, such as rheumatoid arthritis, and those patients improved, that was enough evidence for researchers to start thinking about whether the same approach could reset the immune system in patients with MS. After rigorous pre-clinical testing, the approach was cautiously introduced into clinical trials in the late 1990s.

Since then, people with certain forms of MS have received autologous hematopoietic stem cell transplants in clinical trials worldwide, and many lessons have been learned along the way. For example, in their phase II trial with 24 patients who failed conventional therapy, Drs. Atkins and Freeman found that a very high dose of chemotherapy followed by purified autologous hematopoietic stem cell transplants appeared to have the most impact on preventing ongoing inflammatory activity and progression in these patients. In some cases, disabilities even improved, suggesting that parts of the brain were being repaired. In fact, one patient who received the treatment twelve years ago is still in remission.

But this treatment is not for everyone with MS, and most patients will benefit more from conventional drug therapies. There are very significant risks and side effects of the chemotherapy and transplant regime, including long hospitalization and serious toxicity.

Dr. Atkins highlights a few priorities for better understanding how to use hematopoietic stem cells transplants for MS. The first is finding the minimal dose of chemotherapy that will effectively destroy the immune system without being too toxic, and the second is to understand which patients could benefit most from this therapy and whether it would be better to start the therapy earlier during the treatment pathway. It is also necessary to benchmark this approach against conventional therapies.

This is the next step for Drs. Atkins and Freeman who are organizing a phase III randomized clinical trial to compare the hematopoietic stem cell transplant approach in people with MS who have highly active disease, and who have failed one or two conventional drugs, against individuals with MS who are treated with the best available, approved drug therapy. 

In the future, Dr. Atkins suggests that it might also be worthwhile to combine multiple hematopoietic stem cell treatments to replace the immune system, along with stem cells that can make the brain cell types that repair damaged myelin. His dream is to someday find a way to identify and knock out just the autoimmune cells in MS and encourage the patient’s own stem cells to repopulate the immune system, without actually having to do a transplant. This could become a new treatment paradigm for MS – one where the immune system is repaired rather than suppressed – and it could offer real hope for patients who suffer from the most aggressive forms of the disease.

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  11. Sariah | Oct 18, 2017
    This article is extremely helpful! My grandpa just died of cancer and we couldn't do anything to prevent it despite the many operations over the years. It's good to know that there are clinicians who already performed Autologous Stem Cell Transplantation which resulted in an improved state of patients. I wish we had heard of this sooner. http://regenerativecellinstitute.com/stemcelltherapy.html 

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