Autoimmune Disorders and Stem Cells
Autoimmune Disorders and Stem Cells
Autoimmune disorders are those in which the body’s immune system turns on the body and treats it as foreign, rather than recognizing it as self. This can lead to the destruction of important tissues. Examples of such disorders are lupus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis; there are others. Some are organ specific, while others are widespread and generalized throughout the body. Since the white blood cells which attack the “intruder” originate in the bone marrow, it has been proposed that bone marrow transplants or treatment with stem cells from bone marrow might help cure these diseases. So what is the status?
Overview
The NIH report on stem cells and autoimmune disorders concludes that there is “enormous potential” but significant research still needs to be done. NIH reports specifically on stem cell treatment for patients with lupus. In this research, patient have had the growth of their own stem cells stimulated with growth factors, and then the stem cells are harvested. Other drugs or radiation are then used to kill the existing white blood cells which are mistakenly attacking the body. The harvested stem cells are then transplanted back into the patient, where they mature and restore the immune system. In one study, published in 2000, the researchers did 1 to 3 year follow-ups of 7 patients with lupus who underwent this procedure and found that the patients remained free of active lupus and did not require medication. Further, they had much more diversity of T-cells than patients with lupus usually do.
NIH also reports that there are several risks associated with this procedure (known as autologous transplant). First, the autoimmune disease may flare up because of the use of growth factors; the problem cells can also increase in number. Second, the stem cells that are derived from the patient may be contaminated to some extent by the defective immune cells. Using uncontaminated stem cells derived form another person, whether umbilical cord blood, bone marrow, or embryonic, could cause an immune system response against those cells. The NIH does say that a much better genetic match could likely be obtained with embryonic stem cells than with adult stem cells.
Adidtionally, it has been found in cancer patients who received stem cell transplants that they were more likley to suffer from a number of other non-life threatening ailments such as bone loss or fatigue than patients who had not had transplants. See Blog Post of 9/18/05, Stem Cell Recipients Mostly Healthy 10 years later. I am not aware of such studies being done with people with autominnune disorders, probably because the transplant itself is still unusual.
A study published in Nature in July of 2005 found that studies in animal models found that treatment with stem cell transplants could reverse autoimmunity.
Gene therapy, or modification of some stem cells, is in the research stage in animals but is not available in humans yet.
Treatment
Patients must be able to tolerate the treatment. The full procedure is known to be potentially life-threatening, because of the high levels of toxic drugs that must be used to kill the defective cells. It is still considered “experimental.” This means your insurance company probably won’t pay for it. Here is what Aetna has to say as of November 22, 2005:
Thus far, results have been encouraging; however, they need to be confirmed by
well-designed randomized, controlled studies in view of the well-known difficulty of judging objectively the effect of a treatment in patients with these diseases. Optimization of mobilization, conditioning regimen, as well as graft manipulation is needed to maximize effectiveness without increasing mortality and morbidity. The use of maintenance therapy after autologous stem cell transplantation to prevent relapse needs to be investigated. Furst (2000) noted that stem cell transplantation for the treatment of systemic sclerosis is showing some apparent effectiveness, but its use is only in the pilot stages.
The National Cancer Institute http://www.clinicaltrials.gov/ct/gui/show/NCT00076752 gives a description of the procedure for lupus patients in a clinical trial. I have summarized it below:
The selected patients will have blood drawn seven times from their arm in order to collect the stem cells. They will also receive intravenous administration of three medications (methylprednisolone, rituximab, and cyclophosphamide) to control the lupus, and have a growth factor drug injected under the skin for several days. After the stem cells have been collected, the patient is admitted to the hospital for 8 days of treatment with rituximab, fludarabine, and cyclophosphamide to kill all existing white blood cells. Then the collected stem cells are infused back in. The patient is discharged when he or she feels better and the cells have engrafted and the bone marrow has recovered, usually 2-3 weeks later. There are then frequent follow-up visits.
Clinical Trials
ClinicalTrials.Gov lists the following stem cell trials which are currently recruiting. You can search the website by the study Identifier number to get more information. You can also browse by a specific disease. Many are Phase I Safety Trials.
Hematopoietic Stem Cell Transplantation in Autoimmune-Related Retinopathy(ARRON)
Verified by Northwestern University January 2006
Sponsored by:
Northwestern University
Information provided by:
Northwestern University
ClinicalTrials.gov Identifier:
NCT00278486
Purpose
ARRON is disease believed to be due to immune cells, cells which normally protect the body, but are now attacking the tissue in the retina and/or optic nerve. In addition, the disease may affect the nerves in the ear or other parts of the body .
Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier NCT00278486
Illinois Northwestern University, Feinberg School of Medicine, Chicago, Illinois, 60611, United States; Recruiting
Kimberly Yaung, R.N 312-908-0059 mailto:k-yaung@northwestern.edu?subject=NCT00278486,%20DI%20ARRON%2004:%20-%20%20Hematopoietic%20Stem%20Cell%20Transplantation%20in%20Autoimmune-Related%20Retinopathy(ARRON) Yu Oyama, MD, Principal Investigator
Allogeneic Stem Cell Transplantation in Systemic Lupus Erythematosus
Verified by Northwestern University January 2006
Sponsored by:
Northwestern University
Information provided by:
Northwestern University
ClinicalTrials.gov Identifier:
NCT00278590
Purpose
Systemic lupus erythematosus (SLE) is a multi-system, inflammatory disorder characterized by the production of antibodies that react with many different self-antigens.
Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier NCT00278590
Kimberly Yaung, R.N. 312-908-0059 mailto:k-yaung@northwestern.edu?subject=NCT00278590,%20DI%20SLE.Allo2004:%20-%20%20Allogeneic%20Stem%20Cell%20Transplantation%20in%20Systemic%20Lupus%20Erythematosus
Illinois Northwestern University, Feinberg School of Medicine, Chicago, Illinois, 60611, United States; Recruiting
Kimberly Yaung, RN 312-908-0059 mailto:k-young@northwestern.edu?subject=NCT00278590,%20DI%20SLE.Allo2004:%20-%20%20Allogeneic%20Stem%20Cell%20Transplantation%20in%20Systemic%20Lupus%20Erythematosus Richard Burt, MD, Principal Investigator
Lymphocyte Depletion and Stem Cell Transplantation to Treat Severe Systemic Lupus Erythematosus
Verified by National Institutes of Health Clinical Center (CC) October 31, 2005
Sponsored by:
National Cancer Institute (NCI)
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00076752
Purpose
This study will examine a new approach to treating patient with severe systemic lupus erythematosus (SLE) that involves collecting stem cells (cells produced by the bone marrow that develop into blood cells) from the patient, completely shutting down the patient's immune system, and then giving back the patient's stem cells. SLE is a chronic, inflammatory disorder of the immune system that can affect many organs.
Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier NCT00076752
Maryland National Cancer Institute (NCI), 9000 Rockville Pike, Bethesda, Maryland, 20892, United States; Recruiting
Patient Recruitment and Public Liaison Office 1-800-411-1222 mailto:prpl@mail.cc.nih.gov?subject=NCT00076752,%20040095:%2004-C-0095-%20%20Lymphocyte%20Depletion%20and%20Stem%20Cell%20Transplantation%20to%20Treat%20Severe%20Systemic%20Lupus%20Erythematosus TTY 1-866-411-1010
More Information
Detailed Web Page
Pilot Study of Total Body Irradiation in Combination With Cyclophosphamide, Anti-Thymocyte Globulin, and Autologous CD34-Selected Peripheral Blood Stem Cell Transplantation in Children With Refractory Autoimmune Disorders
Verified by Office of Rare Diseases (ORD) September 2005
Sponsored by:
Fred Hutchinson Cancer Research Center
Information provided by:
Office of Rare Diseases (ORD)
ClinicalTrials.gov Identifier:
NCT00010335
Purpose
OBJECTIVES: I. Determine the safety and long term complications of total body irradiation in combination with cyclophosphamide, anti-thymocyte globulin, and autologous CD34-selected peripheral blood stem cell (PBSC) transplantation in children with refractory autoimmune disorders.
II. Determine the efficacy of this treatment regimen in these patients.
III. Determine the reconstitution of immunity after autologous CD34-selected PBSC transplantation in these patients.
IV. Determine engraftment of autologous CD34-selected PBSC in these patients.
Conditions include Systemic Sclerosis, Systemic Lupus Erythematosus, Dermatomyositis, Juvenile Rheumatoid Arthritis, and Autoimmune Diseases
Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier NCT00010335
Washington Fred Hutchinson Cancer Research Center, Seattle, Washington, 98109, United States; Recruiting
Ann Woolfrey 206-667-4453
Hematopoietic Stem Cell Support in Patients With Autoimmune Bullous Skin Disorders
Verified by Northwestern University January 2006
Sponsored by:
Northwestern University
Information provided by:
Northwestern University
ClinicalTrials.gov Identifier:
NCT00278642
Purpose
Autoimmune Bullous Skin Disorders are believed to be due to immune cells, cells that normally protect the body and are now causing damage to the body.
Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier NCT00278642
Kathleen Quigley, R.N., M.B.A. 312-908-0059 k-quigley@northwestern.edu
Illinois
Northwestern University, Feinberg School of Medicine, Chicago, Illinois, 60611, United States; Recruiting
Kathleen Quigley, RN 312-908-0059 k-quigley@northwestern.edu
Richard Burt, MD, Principal Investigator
Joan Guitart, MD, Sub-Investigator
Yu Oyama, MD, Sub-Investigator
Kathleen Quigley, R.N.;M.B.A., Sub-Investigator
Kimberly Yaung, R.N., Sub-Investigator
Hematopoietic Stem Cell Transplantation in Patients With Antiphospholipid Syndrome
Verified by Northwestern University January 2006
Sponsored by:
Northwestern University
Information provided by:
Northwestern University
ClinicalTrials.gov Identifier:
NCT00278616
Purpose
Antiphospholipid syndrome is disease believed to be due to immune cells, cells which normally protect the body, but are now producing the protein which leads to abnormal clotting in the body.
Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier NCT00278616
Kimberly Yaung, R.N. 312-908-0059 mailto:k-yaung@northwestern.edu?subject=NCT00278616,%20NU%20APS%20AUTO%202004:%20-%20%20Hematopoietic%20Stem%20Cell%20Transplantation%20in%20Patients%20With%20Antiphospholipid%20Syndrome
Illinois Northwestern University, Feinberg School of Medicine, Chicago, Illinois, 60611, United States; Recruiting
Kimberly Yaung, RN 312-908-0059 mailto:k-yaung@northwestern.edu?subject=NCT00278616,%20NU%20APS%20AUTO%202004:%20-%20%20Hematopoietic%20Stem%20Cell%20Transplantation%20in%20Patients%20With%20Antiphospholipid%20Syndrome Richard Burt, MD, Principal InvestigatorLaisvyde Statkute, MD, Sub-InvestigatorYu Oyama, MD, Sub-InvestigatorWalter Barr, MD, Sub-InvestigatorKathleen Quigley, R.N.; M.B.A, Sub-InvestigatorKimberly Yaung, R.N, Sub-Investigator
Stem Cell Support in Patients With Rheumatoid Arthritis
Verified by Northwestern University January 2006
Sponsored by:
Northwestern University
Information provided by:
Northwestern University
ClinicalTrials.gov Identifier:
NCT00278551
Purpose
Rheumatoid arthritis (RA) is a chronic illness, immunologically mediated, probably induced by the exposure to an antigen or antigens, to which immunologic tolerance is lost.
Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier NCT00278551
Katie Weppner, RN 312-908-0059 mailto:c-weppner@northwestern.edu?subject=NCT00278551,%20NU%2096RA1:%20-%20%20Stem%20Cell%20Support%20in%20Patients%20With%20Rheumatoid%20ArthritisKathleen Quigley, R.N.; M.B 312-908-0059 mailto:k-quigley@northwestern.edu?subject=NCT00278551,%20NU%2096RA1:%20-%20%20Stem%20Cell%20Support%20in%20Patients%20With%20Rheumatoid%20Arthritis
Illinois Northwestern University, Feinberg School of Medicine, Chicago, Illinois, 60611, United States; Recruiting
Katie Weppner, RN 312-908-0059 mailto:c-weppner@northwestern.edu?subject=NCT00278551,%20NU%2096RA1:%20-%20%20Stem%20Cell%20Support%20in%20Patients%20With%20Rheumatoid%20Arthritis Richard Burt, MD, Principal InvestigatorWalter Barr, MD, Sub-InvestigatorYu Oyama, MD, Sub-Investigator
A Study in Type 1 Diabetic Patients With Repeated Doses of E1 in Combination With G1
Verified by Transition Therapeutics September 2005
Sponsored by:
Transition Therapeutics
Information provided by:
Transition Therapeutics
ClinicalTrials.gov Identifier:
NCT00239148
Purpose
The purpose of the study is to determine whether E1 and G1 are safe and effective in the treatment of type 1 diabetes.
Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier NCT00239148
Alabama Pinnacle Research Group, Anniston, Alabama, 36207, United States; Recruiting
Ruby Fields 256-236-0055 Ayman Zayed, M.D., Principal Investigator
California Diablo Clinical Research, Walnut Creek, California, 94598, United States; Recruiting
John McAdams 925-930-7267 Ext. 225 Richard Weinstein, M.D., Principal Investigator
New York Diabetes - Endocrinology Center of West New York, Buffalo, New York, 14209, United States; Recruiting
Cathy Gamel 716-887-4486 mailto:cgamel@kaleidahealth.org?subject=NCT00239148,%20INT-201:%20-%20%20A%20Study%20in%20Type%201%20Diabetic%20Patients%20With%20Repeated%20Doses%20of%20E1%20in%20Combination%20With%20G1 Paresh Dandona, M.D., Principal Investigator
Texas Diabetes and Glandular Disease Research Associates, San Antonio, Texas, 78229-4801, United States; Recruiting
INT-201 recruiter 210-705-5614 Sherwyn Schwartz, M.D., Principal Investigator
Resources
Note: Many bone marrow and stem cell transplants take place for cancer patients. Not all of this information will be useful for people with autoimmune disorders, but it gives you a start. This is just a handful. To my Non-America Readers, I apologize for the largely US bias, that was what I found most easily. I am sure there are many other sources out there, this is a smattering and should not be considered definitive.
The Bone Marrow Transplant Institute publishes a book by Susan K. Stewart called “Bone Marrow and Blood Stem Cell Transplants,” available for $8.95. http://www.bmtinfonet.org/transplanthandbook.html
Bone Marrow and Stem Cell Transplant Support Group, http://www.bmtsupport.ie/. Based in Ireland.
National Cancer Institute Fact Sheet: http://www.cancer.gov/cancertopics/factsheet/Therapy/bone-marrow-transplant
Siteman Cancer Center in St. Louis: http://www.siteman.wustl.edu/patient/other_specialized/bone_marrow.shtml
Stem Cell Transplant Program at Northwestern in Chicago: http://www.nmh.org/nmh/specialtiesandservices/servicescenters/sct/main.htm
The Seattle Cancer Care Alliance: http://www.seattlecca.org/patientsandfamilies/adultCare/transplant/DiseasesTreated.htm
Tulane Cancer Center Bone Marrow Transplant: http://www.som.tulane.edu/cancer/bmt.html
NIH Database on Blood and Marrow Stem Cell Transplants: info about at http://stemcells.nih.gov/news/bloodDB.asp. Data at http://www.ncbi.nlm.nih.gov/projects/mhc/MHC.fcgi?cmd=init
