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The body's main line of defense against invasion by infectious organisms is the immune system. To succeed, an immune system must distinguish the many cellular components of its own body (self) from the cells or components of invading organisms (nonself). "Nonself" should be attacked while "self" should not. Therefore, two general types of errors can be made by the immune system. If the immune system fails to quickly detect and destroy an invading organism, an infection will result. However, if the immune system fails to recognize self cells or components and mistakenly attacks them, the result is known as an autoimmune disease.
In recent years, researchers have contemplated the use of stem cells to treat autoimmune disorders. The immune-mediated injury in autoimmune diseases can be organ-specific, such as type 1 diabetes which is the consequence of the destruction of the pancreatic beta islet cells or multiple sclerosis which results from the breakdown of the myelin covering of nerves. These autoimmune diseases are amenable to treatments involving the repair or replacement of damaged or destroyed cells or tissue. In contrast, non-organ-specific autoimmune diseases, such as lupus, are characterized by widespread injury due to immune reactions against many different organs and tissues. No specific antigen has been located as the cause of stiff-person syndrome except for a connection to anti-glycine receptors in the startle response and those antigens associated with paraneoplastic syndrome and PERM. Patients have shown mixed response to IVIG and immunotherapy and SPS is still considered to be autoimmune in nature.
The objective of hematopoietic stem cell therapy is to destroy the mature, long-lived, and auto-reactive immune cells and to generate a new, properly functioning immune system. In most of these trials, the patient's own stem cells have been used in a procedure known as autologous hematopoietic stem cell transplantation. If the stem cells are not autologous (donated by the patient) the patient would require anti-rejection medications which carry their own risks.
First, patients receive injections of a growth factor, which coaxes large numbers of hematopoietic stem cells to be released from the bone marrow into the blood stream. These cells are harvested from the blood, purified away from mature immune cells, and stored.
After sufficient quantities of these cells are obtained, the patient undergoes a regimen of cytotoxic (cell-killing) drug and/or radiation therapy, which eliminates the mature immune cells. For autoimmune diseases, this can include Carmustine, Cytarabine, Melphalan, and antithymocyte globulin.
The hematopoietic stem cells are returned to the patient via a blood transfusion into the circulation where they migrate to the bone marrow and begin to differentiate to become mature immune cells. The body's immune system is then restored. Nonetheless, the recovery phase, until the immune system is reconstituted, represents a period of dramatically increased susceptibility to bacterial, fungal, and viral infection, making this a high-risk therapy.
National Institutes of Health: HSCT explained in detail.
American Cancer Society: SCT what to expect, side effects, complications, recovery
The cost is extremely high ($300,000 to 700,000 US). As of the end of 2014, stem cell transplants are in the research stage, but do offer hope for one day finding cures for many autoimmune diseases.
As of November 30, 2014 at least eight patients have undergone this procedure for SPS. Two are mentioned in the study #1 below. Three have successfully completed the treatment and are in stages of recovery. One did not survive the treatment, but it is not known if it was the process itself or the state of the patient’s health in general.
“Ms van Meurs was Dr Fedorenko’s first SPS patient, and her husband Mark said she died of a heart attack on July 19. “I do know that Rosemary [Ms van Meurs' aunt and carer in Moscow] felt she received the best possible care, especially from Dr Fedorenko,” he said.”
According to Dr. Atkins of the Ottowa project, the outlook for HSCT treatment of SPS is cautiously optimistic.
There are many fraudulent stem cell “therapies” being offered around the globe. Foreign countries and local clinics that offer to inject cord blood or “pleuripotent stem cells” into your veins are skirting the law by promoting it as “alternative” medicine or cosmetic procedure. These practices are highly dangerous (in some cases illegal) scams. Do not attempt them. The only stem cell therapy for SPS is HSCT. Beware-of-stem-cell-therapy-scams-says-fda
1. Sanders S, Bredeson C, Pringle CE, et al. Autologous stem cell transplantation for stiff person sydrome two cases from the Ottowa blood and marrow transplant Program. Arch Neuro. Published online August 25, 2014. Link to article
“Both patients achieved clinical remission with sustained, marked improvement in symptoms and a return to premorbid functioning, now more than 2.5 and 4.5 years after the procedure. Stiff person syndrome represents a novel indication for auto-HSCT. The resolution of clinical manifestations of SPS despite the persistence of anti-glutamic acid decarboxylase antibodies following auto-HSCT suggests that the antibody does not play a direct role in pathogenesis of SPS.”
2. Clow EC, Couban S, Grant IA. Stiff-person syndrome associated with multiple myeloma following autologous bone marrow transplantation. Muscle & Nerve 2008;38:6, 1649-1652. Link to article
“We report a 31-year-old woman who developed SPS after autologous bone marrow transplantation and subsequent interferon treatment for multiple myeloma. Anti-glutamic acid decarboxylase (anti-GAD) antibody serology was positive. The myeloma remains in remission 10 years posttransplant. This is the second report of SPS in a patient with myeloma and the first description of SPS following autologous transplantation.We speculate that an aberrant posttransplant immune response may have caused both the SPS and an autologous graft-versus-myeloma effect, resulting in prolonged remission posttransplant.
3. Tyndall A.. Successes and failures of stem cell transplantation in autoimmune diseases. Hematology Am Soc Hematol Educ Program. 2011;2011:280-4.
Over the past 15 years, more than 1500 patients have received HSCT, mostly autologous, as treatment for a severe autoimmune disease (AD). An overall 85% 5-year survival and 43% progression-free survival was seen, with 100-day transplantation-related mortality (TRM) ranging between 1% (RA) and 11% (SLE and JIA). Approximately 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution.
4. Hügle T, Daikeler T. Stem Cell Transplantation For Autoimmune Diseases. Haematologica February 201095:185-188; Doi:10.3324/haematol.2009.017038. Link to article
CURRENT CLINICAL TRIALS
Autologous hematopoietic stem cell therapy is still in the investigational stages for SPS. These studies are currently conducted in four locations:
1. Dr. Harold Atkins, Ottowa Research Institute, Ottowa, Canda. email@example.com http://www.ohri.ca/home.asp
Dr. Atkins’ Research http://www.ohri.ca/profiles/atkins.asp
2. Dr. Richard Nash, Colorado Blood Cancer Institute, Denver, Colorado, USA., 80218 (720) 754-4800. Callie Redmand (720) 754-4873.
3. Dr. George E. Georges. Fred Hutchinson Cancer Research Center, Seattle, Washington, USA 98109. (206) 667-6886. Bernie McLaughlin (206) 667-4916.
4. Dr. Denis Fedorenko, The A. A. Maximov Dept of Hematogology and Cellular Therapy, Moscow, Russia. +7 495-603-72-24
For up to date information on current and future clinical trials, visit http://www.clinicaltrials.gov.
2. Tina Ceroni
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