Multiple sclerosis is a systemic autoimmune disease that affects the central nervous system, which includes both the brain and spinal cord.
In patients with MS, the immune system attacks the myelin sheath that protects nerve endings and connections. These inflammatory lesions are often visible on MRI scans and progressively impair communication between nerves and motor cells. This disease is particularly feared because it leads to the gradual loss of limb function and movement.
The exact symptoms experienced by a patient with multiple sclerosis vary depending on the areas affected by the autoimmune inflammatory process. However, as demyelinating lesions accumulate, the frequency and severity of disease flare-ups also increase. Over time, patients often develop secondary intractable disease.
Multiple sclerosis (MS) is primarily treated with conventional oral medications or injectable drugs.
Some patients with relapsing-remitting MS respond to these treatments and are able to reduce the frequency of recurrent attacks or prevent them altogether. Unfortunately, those with non-responding disease, as well as the majority of patients with primary or secondary progressive MS, do not respond to conventional therapies. Such patients are often considered incurable.
Autologous Hematopoietic Stem Cell Transplantation (HSCT)
Patients with severe or worsening multiple sclerosis (MS) who do not respond to standard treatments may benefit from immunosuppressive therapies. These treatments sometimes include intense conditioning to remove all mature lymphocytes, including those attacking the body’s own tissues. This process is often paired with autologous hematopoietic stem cell transplantation (HSCT). After the procedure, the patient’s immune system can rebuild itself with newly generated T cells that are trained to tolerate the body’s tissues, potentially stopping the progression of the disease. This process is similar to how self-tolerance is developed in early embryonic stages. However, HSCT is a highly complex treatment and carries significant risks, which limits its use.
Some combination therapies offer similar benefits. These approaches may use immunosuppressive treatments to decrease harmful lymphocytes, followed by growth factors to stimulate the release of stem cells from the bone marrow. These stem cells, along with newly developed healthy T cells, offer a less risky option compared to HSCT, often called “micro-HSCT.”
Mesenchymal Stem Cells in the Treatment of Multiple Sclerosis
Mesenchymal stem cells (MSCs) offer a safer alternative for treating multiple sclerosis due to their ability to reduce inflammation and regulate the immune system. These cells can be obtained from the patient’s own body or from donated placenta and umbilical cord tissue. MSCs are versatile and can potentially transform into oligodendrocytes, the cells responsible for producing myelin, which helps repair damaged nerves. Additionally, nanoparticles released by MSCs may encourage the patient’s own MSCs to repair myelin.
Innovative targeting methods enhance the potential of circulating MSCs to reach the central nervous system (CNS). For example:
- Acoustic Shockwave Therapy (AST): Non-invasive low-energy shockwaves dilate blood vessels, increasing the flow of regulatory cells to the CNS.
- Low-Level Laser Therapy (LLLT): Multi-color laser light stimulates circulating MSCs, enhancing their regenerative properties.
- Deep Transcranial Magnetic Stimulation (dTMS): This device can complement MSC-based therapies to optimize patient outcomes.
The combination of these supportive technologies — AST, LLLT, and dTMS — can be applied to both patients receiving MSCs expanded ex vivo and those treated with enriched autologous multipotent stem cells.
Based on preclinical studies and clinical experience, a significant number of MS patients who were unresponsive to conventional treatments have shown improvement and, in some cases, were even cured with MSC-based outpatient therapies.
However, regulatory challenges remain. The use of MSCs enriched ex vivo in cell-processing centers is not yet approved by many regulatory authorities. As a result, mesenchymal stem cells for MS and other resistant autoimmune diseases can currently only be performed in our satellite clinics located in countries with more permissive regulations.
Our Scientific Research and Patents on Stem Cell Treatments
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Karussis D, Grigoriadis S, Polyzoidou E, Grigoriadis N, Slavin S, Abramsky O.
Neuroprotection in multiple sclerosis. Clin Neurol Neurosurg. 2006 Mar; 108(3):250-4. -
Burt RK, Cohen B, Rose J, Petersen F, Oyama Y, Stefoski D, Katsamakis G, Carrier E, Kozak T, Muraro PA, Martin R, Hintzen R, Slavin S, Karussis D, Haggiag S, Voltarelli JC, Ellison GW, Jovanovic B, Popat U, McGuirk J, Statkute L, Verda L, Haas J, Arnold R.
Hematopoietic stem cell transplantation for multiple sclerosis. Arch Neurol. 2005 Jun; 62(6):860-4. (Review) -
Slavin S, Kurkalli BG, Karussis D.
The potential use of adult stem cells for the treatment of multiple sclerosis and other neurodegenerative disorders.Clin Neurol Neurosurg. 2008 Nov; 110(9):943-6. -
Karussis D, Kassis I, Kurkalli BG, Slavin S.
Immunomodulation and neuroprotection with mesenchymal bone marrow stem cells (MSCs): a proposed treatment for multiple sclerosis and other neuroimmunological/neurodegenerative diseases. J Neurol Sci. 2008 Feb 15; 265(1-2):131-5. -
Kassis I, Grigoriadis N, Gowda-Kurkalli B, Mizrachi-Kol R, Ben-Hur R, Slavin S, Abramsky O, Karussis D.
Neuroprotection and immunomodulation with mesenchymal stem cells in chronic experimental autoimmune encephalomyelitis. Arch Neurol. 2008; 65(6):753-761. -
Karussis D, Karageorgiou C, Vaknin-Dembinsky A, Gowda-Kurkalli B, Gomori JM, Kassis I, Bulte JW, Petrou P, Ben-Hur T, Abramsky O, Slavin S.
Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol. 2010 Oct; 67(10):1187-94. -
Freedman MS, Bar-Or A, Atkins HL, Karussis D, Frassoni F, Lazarus H, Scolding N, Slavin S, Le Blanc K, Uccelli A.
The therapeutic potential of mesenchymal stem cell transplantation as a treatment for multiple sclerosis: consensus report of the International MSCT Study Group. Mult Scler. 2010 Apr; 16(4):503-10.
Successful treatment of autoimmune disease in (NZB/NZW)F1 female mice using fractionated total lymphoid irradiation. Slavin S. Proc Natl Acad Sci USA. 1979;76:5274-5276.
The use of total lymphoid irradiation (TLI) as immunosuppressive therapy for organ allotransplantation and autoimmune diseases. Fuks Z, Slavin S. Int J Rad Oncol Biol Phys. 1981;7:79-82.
Regulation of the immune response in experimental models of autoimmune disorders. Part 1: Immunocompetence and transplantation tolerance in (NZB x NZW)F1 hybrid mice immunosuppressed with total lymphoid irradiation and in reconstituted bone marrow chimeras. Moscovitch M, Slavin S. J Clin Lab Immunol. 1983;4:185-191.
Regulation of the immune response in experimental models of autoimmune disorders. Part 2: Induction of suppressor cells of the mixed lymphocyte culture in adult (NZB x NZW)F1 mice using total lymphoid irradiation. Moscovitch M, Slavin S. J Clin Lab Immunol. 1983;11:67-74.
Successful treatment of autoimmune manifestations in MRL/1 and MRL/n mice using total lymphoid irradiation (TLI). Moscovitch M, Rosenmann E, Neeman Z, Slavin S. Exp Molec Pathol. 1983;38:33-47.
Total lymphoid irradiation prevents diabetes mellitus in the bio-breeding/Worcester (BB/W) rat. Rossini AA, Slavin S, Woda BA, Geisberg M, Like AA, Mordes JP. Diabetes. 1984;33:543-547.
The use of total lymphoid irradiation (TLI) for the treatment of autoimmune disorders. Slavin S. Isr J Med Sci.1988;24:375-8.
Induction of tolerance to allo- and self-antigens with syngeneic bone marrow transplantation. Slavin S, Karussis DM, Weiss L, Karussis-Vourka U, Abramsky O. Transpl Proc. 1993;25:1274-1275.
Immunomodulation of autoimmunity in MRL/1pr mice with syngeneic bone marrow transplantation (SBMT).Karussis DM, Vourka-Karussis U, Lehmann D, Abramsky O, Ben-Nun A, Slavin S. Clin Exp Immunol.1995;100(1):111-117.
Induction of tolerance to experimental anti-phospholipid syndrome (APS) by syngeneic bone marrow cell transplantation. Blank M, Tomer Y, Slavin S, Shoenfeld Y. Scand J Immunol. 1995;42:226-234.
Autologous and allogeneic stem cell transplantation for the treatment of autoimmune diseases as a potential new approach. Slavin S. In: The Decade of Autoimmunity. Yehuda Shoenfeld (Ed.), Elsevier, 1999:399-408.
Bone marrow transplantation for cancer and autoimmunity. Slavin S, Nagler A. In: Cancer and Autoimmunity. Y. Shoenfeld, E. Gershwin (Eds.), Elsevier, 2000:409-421.
Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: Getting closer to a cure? Burt RK, Slavin S, Burns WH, Marmont AM. Blood. 2001;99(3):768-784.
Non-myeloablative stem cell transplantation for autoimmune diseases. Burt RK, Verda L, Oyama Y, Statkute L, Slavin S. Springer Semin Immun. 2004;26:57–69.
Allogeneic hematopoietic stem cell transplantation for autoimmune diseases. Slavin S, Marmont A, Burt R. In: Stem Cell Therapy for Autoimmune Disease. R.K. Burt, A.M. Marmont (Eds.), Landes Bioscience, Texas, USA, 2004:474-478.
Non-myeloablative stem cell transplantation for autoimmune diseases. Burt RK, Verda L, Oyama Y, Statkute L, Slavin S. In: Seminars in Immunopathology. Springer, Heidelberg, Germany, 2004;26:57-69.
Hematopoietic stem cell transplantation for multiple sclerosis. Burt RK, Cohen B, Rose J, Petersen F, Oyama Y, Stefoski D, Katsamakis G, Carrier E, Kozak T, Muraro PA, Martin R, Hintzen R, Slavin S, Karussis D, Haggiag S, Voltarelli JC, Ellison GW, Jovanovic B, Popap U, McGuirk J, Statkute L, Verda L, Haas J, Arnold R. Arch Neurol.2005;62(6):860-864.
1. Patent number: 10421961
Name: Methods, systems, and compositions for neuronal differentiation of multipotent stromal cells
Abstract: Some embodiments of the invention comprise methods, systems, and compositions to selectively induce, whether in vitro or in vivo, the neuronal differentiation of multipotent stromal cells through the application of microRNAs, including but not limited to miRNA-124, miRNA-137 and/or miRNA-9* expression products of those miRNAs, and molecules and compositions containing functional elements of those miRNAs. Some embodiments of the invention also comprise the therapeutic administration and use of such induced cells to treat mammalian injuries and diseases, including but not limited to, nervous system injuries or diseases that may otherwise result in decreased cell or system function.
Type: Grant
Filed: June 10, 2010
Date of Patent: September 24, 2019
Assignee: EXOSTEM BIOTEC LTD
Inventors: Shimon Slavin, Chaya Brodie
Link: https://patents.justia.com/patent/10421961
2. Patent number: 10034902
Name: MicroRNAs for the generation of astrocytes
Abstract: A method of generating a population of cells useful for treating a nerve disease or disorder in a subject, the method comprising up-regulating a level of at least one exogenous miRNA in mesenchymal stem cells (MSCs) and/or down-regulating a level of at least one miRNA using a polynucleotide agent that hybridizes to the miRNA, thereby generating the population of cells useful for treating the nerve disease or disorder. Isolated populations of cells with an astrocytic phenotype generated thereby and uses thereof are also provided.
Type: Grant
Filed: February 21, 2013
Date of Patent: July 31, 2018
Assignees: EXOSTEM BIOTEC LTD., HENRY FORD HEALTH SYSTEM
Inventors: Shimon Slavin, Chaya Brodie
Link: https://patents.justia.com/patent/10034902
3. Patent number: 9803175
Name: Generation of neural stem cells and motor neurons
Abstract: A method of generating neural stem cells or motor neurons is disclosed, the method comprising up-regulating a level of at least one exogenous miRNA and/or down-regulating at least one miRNA using an agent which hybridizes to the miRNA in mesenchymal stem cells (MSCs) or down-regulating Related to testis-specific, vespid and pathogenesis protein 1 (RTVP-1).
Type: Grant
Filed: February 21, 2013
Date of Patent: October 31, 2017
Assignees: EXOSTEM BIOTEC LTD., HENRY FORD HEALTH SYSTEM
Inventors: Shimon Slavin, Chaya Brodie
Link: https://patents.justia.com/patent/9803175
4. Patent number: 9783781
Name: Methods of generating oligodendrocytes and cell populations comprising same
Abstract: A method of generating a population of cells useful for treating a brain disorder in a subject is disclosed. The method comprises contacting mesenchymal stem cells (MSCs) with at least one exogenous miRNA having a nucleic acid sequence at least 90% identical to a sequence selected from the group consisting of SEQ ID NOs: 15-19 and 27-35, thereby generating the population of cells and/or generating neurotrophic factors that may provide important signals to damaged tissues or locally residing stem cells. MSCs differentiated by miRs may also secrete miRs and deliver them to adjacent cells and therefore provide important signals to neighboring endogenous normal or malignant cells.
Type: Grant
Filed: August 14, 2011
Date of Patent: October 10, 2017
Assignee: EXOSTEM BIOTEC LTD.
Inventors: Shimon Slavin, Chaya Brodie
Link: https://patents.justia.com/patent/9783781
