Autologous Hematopoietic Stem Cell Transplant: a new hope for Multiple Sclerosis patients

By Cristina Riquelme Vano

Multiple sclerosis (MS) is an autoimmune disease where the immune system attacks the myelin, the protective sheath that covers nerve fibers of the central nervous system (CNS) causing inflammation. Myelin also helps the nerves conduct electrical signals quickly and efficiently. When the myelin sheath disappears or is damaged in multiple areas, it leaves a scar, or sclerosis which mainly affects the brain, spinal cord, and optic nerves. This can lead to a wide range of symptoms throughout the body such as weakness, tingling in the limbs, chronic pain, blurred vision which in severe MS patients can experience paralysis and vision loss (Brazier, 2019).

The possibility to obtain curative therapy in autoimmune diseases such as MS remains unfeasible. There is no current cure for MS but there are forms of treatment to slow MS progression and relieve the symptoms. Conventional therapies for MS are based on the use of immune-modulating agents (interferons or glatiramer acetate) and anti-inflammatory and immune suppressive drugs (glucocorticoids, methotrexate, and mitoxantrone) approved by the Food and Drug Administration (FDA) (Medications, 2020). However, these drugs are not able to stop the destruction of nerve tissue and have several limitations like the apparition of side effects. Thus, the importance of finding other strategies to treat MS.

Autologous Hematopoietic Stem Cell Transplant (aHSCT) has been recently proposed as treatment of MS, giving patients with MS new hope in halting their disease progression. While the therapy is a form of stem cell transplantation, the stem cells are not the vital part of the process. In fact, the key element is the infusion of chemotherapy drugs to suppress the MS patient immune system (Franks, 2017). Different blood cells are involved in the abnormal immune response seen in MS. Two important types of immune cells are T cells and B cells. T cells become activated in the lymph system and in MS patients, enter the CNS through blood vessels. Once in the CNS, T cells release chemicals that cause inflammation and damage. This results in damage to myelin, nerve fibers and the cells that make myelin. T cells are also important to help activate B cells and call on other immune system cells to participate in the immune attack. T regulatory cells, a type of T cell, turn off inflammation. In MS patients, T regulatory cells do not function correctly and do not effectively turn off inflammation. B cells become activated with the help of T cells. B cells produce antibodies and stimulate other proteins and in MS cause damage in the CNS (Immune-Mediated Disease, 2020). 

Autologous (stem cells received are from the patient itself) HSCT for MS treatment is nonmyeloablative. Nonmyeloablative uses lower-dose, more tolerable chemotherapy drugs to suppress the immune system in contrast to myeloablative aHSCT which uses high-dose chemotherapy drugs to destroy the immune system (e.g in leukaemia and lymphoma treatment). aHSCT for MS treatment works by extracting blood from the MS patient and isolating its hematopoietic stem cells (HSCs) for the later transplant. HSCs are multipotent stem cells that give rise to all blood cells while retaining its self-renewal capacity. Therefore, after low dosage of chemotherapeutic drugs is administered to the MS patient, HSCs are transplanted and can regenerate a new and antigen naive immune system, due to its multipotency (Franks, 2017). 

An extremely high success rate has been claimed for this treatment, but it is still regarded as experimental. Atkins, Atkins et al. reported severely disabled people with MS able to walk, cycle, and even ski after aHSCT (Atkins et al., 2016). The story made newspaper headlines around the world. However, scientists from the University Hospital Basel had previously encountered difficulties with MS patients treated with aHSCT, such as significant morbidity and mortality, therefore not yet standard of care. Whether aHSCT is or not an effective treatment to MS remains unclear but remains as hope for MS patients.

References:

Brazier, Y., 2019. Multiple Sclerosis (MS): Types, Symptoms, And Causes. [online] MedicalNewsToday. Available at: <https://www.medicalnewstoday.com/articles/37556&gt; [Accessed 24 October 2020].

National Multiple Sclerosis Society. 2020. Medications. [online] Available at: <https://www.nationalmssociety.org/Treating-MS/Medications&gt; [Accessed 24 October 2020].

Franks, I., 2017. What Is Hematopoietic Stem Cell Transplantation?. [online] MedicalNewsToday. Available at: <https://www.medicalnewstoday.com/articles/318091#Donor-selection&gt; [Accessed 24 October 2020].

National Multiple Sclerosis Society. 2020. Immune-Mediated Disease. [online] Available at: <https://www.nationalmssociety.org/What-is-MS/Definition-of-MS/Immune-mediated-disease&gt; [Accessed 24 October 2020].

Atkins, H., Bowman, M., Allan, D., Anstee, G., Arnold, D., Bar-Or, A., Bence-Bruckler, I., Birch, P., Bredeson, C., Chen, J., Fergusson, D., Halpenny, M., Hamelin, L., Huebsch, L., Hutton, B., Laneuville, P., Lapierre, Y., Lee, H., Martin, L., McDiarmid, S., O’Connor, P., Ramsay, T., Sabloff, M., Walker, L. and Freedman, M., 2016. Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial. The Lancet, 388(10044), pp.576-585.

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