Alternative Therapies for Multiple Sclerosis ©

By David Steenblock, M.S., D.O.

This review is for educational purposes only and is not intended to be a substitute for your physician's advice.

The "First Cell" (fertilized egg) at the beginning of life is "totipotent," capable of generating every other cell of the body. When this First Cell divides into three embryonic layers (the ectoderm, mesoderm and endoderm), the daughter cells become "multipotent", able to transform into a variety of cell types, but unable to make an entire individual. CD34 (+) is a purified multipotent stem cell found in bone marrow and umbilical cord blood. These stem cells are capable of "homing" to an injured area where they move into the tissue and proliferate into the specific cells needed to repair the tissue. CD34(+) cells, and especially its CD133 subset, are capable of balancing the immune system as well as transforming into neuroprotective glia and myelin-producing oligodendrocytes and astrocytes. Such potency makes CD34+ stem cells a valuable treatment modality in immune disorders of the central nervous system such as Multiple Sclerosis.

Remyelination Studies

Since 1965, Scientists have observed spontaneous myelin repair. However, the many factors involved in promoting a more profound repair than what occurs naturally and maintaining that repair are still being investigated.

In the relapsing-remitting pattern, some remyelination is observed. Spontaneous remyelination is thought to be caused by previously quiescent oligodendrocyte progenitor cells rather than mature oligodendrocytes. Platelet-derived growth factor has been found to stimulate the multiplication and growth of these oligodendrocyte progenitor cells.

In the progressive degeneration pattern, oligodendrocytes are destroyed. Implants of oligodendrocyte progenitor cells into MS patients have been successful. However, while Schwann cells also promote remyelination, their implants have a greater risk of fibroblast overgrowth that subsequently can destroy axonal pathways. Glial cell implants have had good results in creating oligodenrocytes (6).

In an animal study, neural stem cells were transplanted into rats with experimental autoimmune encephalomyelitis (an animal model for MS). The cells migrated into the brain or spinal cord, exclusively into the inflamed white matter but not into adjacent gray matter regions. After two weeks, many transplanted cells had migrated into distant white matter tracts and acquired astroglial and oligodendroglial lineages. The authors conclude that the inflammatory process may attract the migration of transplanted precursor cells into the brain parenchyma (connective tissue network) (5).

The effectiveness of stem cells in treating autoimmune disease was observed in patients who received allogeneic hematopioetic stem cell transplants for leukemia and aplasia who also suffered from severe autoimmune disorders (lupus and rheumatoid arthritis).

In 1998, Burt and coworkers treated 10 patients having autoimmune disease (6 patients with MS, 2 with Lupus, and 2 with rheumatoid arthritis) with autologous hematopoietic stem cells from bone marrow or mobilized from peripheral blood. CD 34+ stem cells were reinfused after either myelosuppressive conditioning with cyclophosphamide, methylprednisolone and antithymocyte globulin or myeloablative conditioning with total body irradiation, methylprednisolone and cyclophosphamide. Regimen-related nonhema-topoietic toxicity was minimal. All patients improved or had stabilization of disease for 5-17 months. The author concluded that T cell-depleted hematopoietic stem cell transplantation can be performed safely in patients with severe and debilitating autoimmune disease (10).

Dr. Ouyang and associates of Nanjing University School of Medicine, China demonstrated positive results in a patient with progressive multiple sclerosis who received an autologous peripheral blood stem cell transplantation. The patient showed clinical remission and there was no relapse at the 6 month follow-up. The authors conclude that auto-Peripheral Blood Stem Cell Transplantation is effective and safe for progressive multiple sclerosis (65).

An MRI study of MS patients who received autologous hematopoietic stem cell transplantations showed disappearance of enhanced T1 brain lesions as well as a reduction in the T2 lesion load 18 months after the transplant. These findings correlated with clinical stabilization in the patients (74).

In a multicenter Phase II study by Fassas and coworkers investigating autologous hematopoietic stem cell transplantation for multiple sclerosis, 85 patients with progressive MS (with a median Extended Disability Status Scale score of 6.5) were treated in 20 European centers. Neurological improvement was seen in 18 patients (21%). Confirmed progression-free survival was seen in 74% of the patients at 3 years. Disease progression was seen in 20%. The authors conclude that autologous HSCT early results are positive and feasible for the management of progressive MS (23).

In a Phase II report by Carreras and associates, the authors used CD34+ cell transplantation in 15 Multiple Sclerosis patients. Patients were selected who had advanced secondary progressive or relapsing-remitting MS or who showed worsening of the extended disability status scale despite interferon and other immunotherapies. They were treated with Cyclophosphamide, granulocyte colony stimulating factor, BCNU, Antithymocyte Globules, Methyl Prednisolone, MESNA, Cipor, Fluconoyol, and Acyclovir, Pentomidine, and Trimethoprim Sulfamethoxzaole Immunoglobins. There were a number of complications from this combination of powerful drugs. At 12 months, the Extended Disability Status Scale had improved in three patients, worsened in two and remained stable in nine. Despite withdrawal of all immunosuppressive therapy, only two patients had relapses. The authors conclude that CD34+ autologous stem cell transplantation using BCNU, Cylophosphamide and Antithymocyte Globules as conditioning regimen has an acceptable toxicity and clearly reduces the progression of Multiple Sclerosis (12).

These results using peripheral blood stem cell mobilization techniques with powerful immune suppressants, antibiotics, antifungals and steroids had a number of side effects with only marginal effectiveness. One factor is that some of these therapies actually inhibit stem cell growth and proliferation. When compared with the case studies to date of umbilical cord CD34+ stem cell transplantation given alone without additional medications, the umbilical cord stem cells show much greater success with virtually no side effects.

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