September 12, 2016

Early findings from a study could make rebooting the immune system using stem cell transplantation safer as an MS treatment in the future


Hematopoietic stem cells (HSCs) constantly produce new blood and immune cells from deep within the bone marrow, making them the building blocks of the blood and immune system. Since the 1960s, scientists have been refining a stem cell transplantation technique to treat certain types of blood cancers like lymphoma. By destroying a person’s diseased immune system with chemotherapy and transplanting fresh HSCs, scientists are able to rebuild a healthy immune system.

In June of 2016, Drs. Mark Freedman and Harry Atkins published the results of the Canadian BMT Trial, in which they use a combination of chemotherapy and HSC transplantation to successfully reboot the immune systems of 23 people with a highly aggressive form of MS. The treatment halted the brain inflammation associated with MS and, for some, reversed MS-related disabilities. The participants of the study were chosen based on the nature of their MS – aggressive and unresponsive to immune-modulating therapies. The procedure carried a significant degree of risk due to the high dose of chemotherapy necessary to destroy the participants’ existing immune system.

Because of the risks associated with these types of replacement therapies, researchers are constantly looking for better and safer ways to eliminate the disease immune system in preparation for a stem cell transplant. In a study published in Science Translational Medicine, Dr. Judith Shizuru and a team of scientists from Stanford University have made significant inroads in solving this dilemma. Instead of using intensive radiation or chemotherapy, they experimented with using two biological compounds to remove HSCs. In their own words, this research “has the potential to transform the practice of HSC transplantation and enable its use in a wider spectrum of patients”.


Dr. Shizuru’s group used two compounds to eliminate HSCs in mice. The first was an antibody that targeted c-Kit, a protein that is essential for the maintenance and survival of HSCs in the bone marrow. The second was a drug that blocked the function of CD47, a protein found on the surface of HSCs (as well as many other cell types) that sends a “don’t destroy me” signal to the immune system.

By itself, the c-Kit targeting antibody was only able to eliminate HSCs in mice genetically engineered to have weak immune systems, and had little to no effect in mice with a fully functioning immune system. Based on prior evidence that blocking CD47 could enhance the ability of antibodies to help destroy certain types of cells, the researchers tested whether blocking CD47 could improve the c-Kit targeting antibody’s ability to remove HSCs in immune-healthy mice.


By giving the c-Kit targeting antibody in combination with a CD47 blocking compound, the researchers were able to eliminate over 99% of all HSCs in healthy animals. Once the HSCs were removed, the researchers successfully transplanted donor HSCs into the mice. Over the next twenty weeks these donor stem cells gave rise to new blood and immune cells, indicating the HSCs had fully incorporated and begun rebuilding the immune system. Importantly, the procedure had relatively few toxic effects on the mice.


A major limitation of current HSC transplantation procedures is the use of harmful radiation and chemotherapy to destroy stem cells, leading Dr. Shizuru and team to look for an effective and safer solution. The combination of c-Kit targeting antibody and CD47 blocking compound led to extensive removal of HSCs in mice, creating the conditions necessary for transplantation. Dr. Shizuru’s findings could help reduce the risks associated with HSC transplantation procedures, such as the one advanced by Dr. Freedman and Dr. Atkin for the treatment of MS.

This is an early study that has several important limitations. Firstly, the study was done in mice, and it is too early to tell if the drugs tested in the study are safe to use in humans. Secondly, the study did not test whether the procedure could treat MS-like disease activity in mice. More extensive studies in animals with an MS-like disease, followed by clinical trials, will be necessary to determine if the use of these drugs could one day serve as a safe and viable alternative to the use of radiation and chemotherapy in stem cell replacement procedures for people living with MS. The MS Society will closely monitor continued development of this therapeutic approach based on the promising results of this study.


Chhabra A et al. (2016) Hematopoietic stem cell transplantation in immunocompetent hosts without radiation or chemotherapy. Science Translational Medicine. 8(351): 351ra105. doi: 10.1126/scitranslmed.aae0501.