By Ajay Macherla, Downingtown STEM Academy, Downingtown, Pennsylvania, USA
Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system and the brain. The immune system, during MS, mistakenly attacks the protective myelin sheath of neurons, leading to demyelination and inflammation. Without this protective layer, neurons cannot send signals effectively to other parts of the body, leading to frequent cramps, vertigo, muscle spasms, urination problems, gait, and vision loss. Unfortunately, as of now, no definitive cure has been discovered to completely eliminate the effects of MS (Ghasemi et al., 2017).
Although MS rarely kills, it drastically reduces quality of life and serves as a catalyst for more fatal diseases in a snowball effect. Furthermore, according to the National Multiple Sclerosis Society, over 2.8 million people worldwide suffer from MS as of September 2020 (Updated Atlas, 2020).
Figure 1. Global prevalence of MS per 100,000 inhabitants (Goodin, 2014).
Figure 1 provides an interesting perspective on the concentration of MS in the United States, Canada, and Europe. This clustering may be attributed to genetic risk predispositions, although details still need to be further researched (Waubant et al., 2019). Environmental factors, such as climate, may explain the clustering of MS prevalence in these countries. A study published in 2017 found a correlation between the level of serum vitamin D, which is influenced by the amount of available sunlight, and MS risk (Sintzel et al., 2017). As northern countries may have less sunlight available than southern ones, it could mean that northern patients typically have less vitamin D than their southern counterparts.
Clearly, a viable and effective treatment for MS is much needed.
Fortunately, recent advancements in stem cell research may be pointing in the right direction. The implementation of autologous hematopoietic stem cell transplantation (aHSCT) has been discovered to be more effective in alleviating the symptoms of MS compared to other treatments available. In essence, the treatment aims to “reprogram” the immune system in the effort to eliminate the autoimmune nature of MS (Snowden et al., 2018).
The first step in administering this therapy is to harvest the autologous hematopoietic stem cells (aHSC), which can be gathered from the bone marrow or peripheral blood using leukapheresis. This allows scientists to extract and isolate aHSC from the blood, which can then be stored in cell banks and other storage units for use when necessary (Gavriilaki et al., 2019).
When a patient is admitted to a healthcare facility, a series of conditioning steps must be conducted. First, chemotherapy or immunoablation may be administered, along with therapeutic antibodies such as antithymocyte globulin (ATG). Once these procedures are completed, the patient is ready to have aHSC infused (Ismail et al., 2019).
Once the stem cells are infused into the patient, a period known as the aplastic phase occurs. This is when the patient’s immune system is too weak to perform its usual functions. Physicians must administer therapeutic antibiotics, intense care, and monitoring two weeks post-transplantation. This will ensure that the patient does not experience any negative side-effects due to either the chemotherapy, immunoablation, or the aHSC infusion (Cuascut & Hutton, 2019).
Figure 2. Diagram detailing the process of aHSCT (Roberts et al., 2020).
Clinical and experimental studies into the application of aHSCT in autoimmune diseases have been conducted since the 1990s, but recent evidence has shown its potential feasibility in the treatment of MS.
As scientists continue to tackle the now year-old COVID-19 pandemic, it is important that we are also making advancements in diseases that have haunted us for years. Hopefully, aHSCT will be effective in treating and possibly curing MS.
However, this is not to say that the aHSCT comes without limitations. Physicians must consider the disadvantages of any treatment they administer to their patients. For one, there could be safety and toxicity concerns with aHSCT, primarily due to the chemotherapy procedure that is necessary for conditioning the patient for the aHSC infusion.
Luckily, the same review reports that “acute toxicities such as alopecia, infections, mucositis, and gastrointestinal symptoms [due to chemotherapy in aHSCT] are addressed by proper supportive care” (Gavriilaki et al., 2019). The need for constant supervision and care for MS patients during aHSCT must be stressed.
Transplant units in some facilities may not have access to the proper medical equipment in order to effectively execute the procedure. This will mean that some areas, particularly neighborhoods of low socio-economic status, may not have adequate access to aHSCT. Furthermore, issues in regards to healthcare reimbursements, which varies based on the healthcare system, need to be addressed (Gavriilaki et al., 2019).
Nevertheless, these limitations should only fuel scientists to discover new innovative methods to combat these disadvantages and develop a new treatment with no downsides. Through trial-and-error –– and a lot of time –– we may very well have a cure for MS.
References
Cuascut, F., & Hutton, G. (2019). Stem Cell-Based Therapies for Multiple Sclerosis: Current Perspectives. Biomedicines, 7(2), 26. https://doi.org/10.3390/biomedicines7020026
Gavriilaki, M., Sakellari, I., Gavriilaki, E., Kimiskidis, V. K., & Anagnostopoulos, A. (2019). Autologous Hematopoietic Cell Transplantation in Multiple Sclerosis: Changing Paradigms in the Era of Novel Agents. Stem Cells International, 2019, 1-9. https://doi.org/10.1155/2019/5840286
Ghasemi, N., Razavi, S., & Nikzad, E. (2017). Multiple Sclerosis: Pathogenesis, Symptoms, Diagnoses and Cell-Based Therapy. Cell J (Yakhteh), 19(1). https://doi.org/10.22074/cellj.2016.4867
Goodin, D. S. (2014). The epidemiology of multiple sclerosis. Handbook of Clinical Neurology, 231-266. https://doi.org/10.1016/B978-0-444-52001-2.00010-8
Ismail, A., Sharrack, B., Saccardi, R., Moore, J. J., & Snowden, J. A. (2019). Autologous haematopoietic stem cell therapy for multiple sclerosis: A review for supportive care clinicians on behalf of the Autoimmune Diseases Working Party of the European Society for Blood and Marrow Transplantation. Current Opinion in Supportive & Palliative Care, 13(4), 394-401. https://doi.org/10.1097/SPC.0000000000000466
Mariottini, A., Innocenti, C., Forci, B., Magnani, E., Mechi, C., Barilaro, A., Nistri, R., Fani, A., Saccardi, R., Massacesi, L., & Repice, A. M. (2018). Safety and efficacy of autologous hematopoietic stem‐cell transplantation following natalizumab discontinuation in aggressive multiple sclerosis. European Journal of Neurology, 26(4), 624-630. https://doi.org/10.1111/ene.13866
Roberts, F., Hobbs, H., Jessop, H., Bozzolini, C., Burman, J., Greco, R., Ismail, A., Kazmi, M., Kirgizov, K., Mancardi, G., Mawson, S., Muraro, P. A., Puyade, M., Saccardi, R., Withers, B., Verhoeven, B., Sharrack, B., & Snowden, J. A. (2020). Rehabilitation Before and After Autologous Haematopoietic Stem Cell Transplantation (AHSCT) for Patients With Multiple Sclerosis (MS): Consensus Guidelines and Recommendations for Best Clinical Practice on Behalf of the Autoimmune Diseases Working Party, Nurses Group, and Patient Advocacy Committee of the European Society for Blood and Marrow Transplantation (EBMT). Frontiers in Neurology, 11. https://doi.org/10.3389/fneur.2020.556141
Sintzel, M. B., Rametta, M., & Reder, A. T. (2017). Vitamin D and Multiple Sclerosis: A Comprehensive Review. Neurology and Therapy, 7(1), 59-85. https://doi.org/10.1007/s40120-017-0086-4
Snowden, J. A., Sharrack, B., Akil, M., Kiely, D. G., Lobo, A., Kazmi, M., Muraro, P. A., & Lindsay, J. O. (2018). Autologous haematopoietic stem cell transplantation (aHSCT) for severe resistant autoimmune and inflammatory diseases – a guide for the generalist. Clinical Medicine, 18(4), 329-334. https://doi.org/10.7861/clinmedicine.18-4-329
Updated Atlas of MS Shows Over 2.8 Million People Worldwide Have Multiple Sclerosis -- with Nearly 1 Million in the US. (2020, September 11). National Multiple Sclerosis Society. https://www.nationalmssociety.org/About-the-Society/News/Updated-Atlas-of-MS-Shows-Over-2-8-million-People
Waubant, E., Lucas, R., Mowry, E., Graves, J., Olsson, T., Alfredsson, L., & Langer‐Gould, A. (2019). Environmental and genetic risk factors for MS: An integrated review. Annals of Clinical and Translational Neurology, 6(9), 1905-1922. https://doi.org/10.1002/acn3.50862