clinical study.
In another clinical study, the ideal conditioning drug is being investigated in combination with the introduction of bone marrow–derived stem cells. Similar to the previously described clinical trial, this study aims to establish mixed chimerism, yet using the optimal conditioning drug. Current medications administered for conditioning prior to kidney transplant include sirolimus, phycophenolate mofetil, and tacrolimus.
A monoclonal antibody known as alemtuzumab has also been employed for conditioning of patients; it acts by binding and depleting T lymphocytes of the bone marrow, thus preventing the development of an immune response. In the clinical study, alemtuzumab is administered to destroy the lymphocytes of the patient right at the time of transplantation. This is then immediately followed by the introduction of bone marrow–derived stem cells that would subsequently differentiate into new T lymphocytes that are expected to recognize the new kidney as part of its own system and thus would not elicit any immune response against the transplanted organ. Other parallel clinical trials are being conducted around the United States that are investigating the use of other conditioning drugs in combination with the bone marrow–derived stem cells. These drugs include cyclosporine, fludarabine phosphate, pentostatin, and anti-interleukin-2 receptor antibody, also known as basiliximab.
There are also investigations that are currently assessing the efficacy of the combination consisting of conditioning drugs, irradiation, and the administration of bone marrow–derived stem cells in preventing the development of graft-versus-host disease in renal transplant patients.
Rhea U. Vallente
Independent Scholar
See Also: Graft Failure, Graft-Versus-Host Disease; Kidney Disease; Kidney: Cell Types Composing the Tissue; Kidney: Current Research on Isolation or Production of Therapeutic Cells; Kidney: Development and Regeneration Potential; Kidney: Major Pathologies; Kidney: Stem and Progenitor Cells in Adults.
Further Readings
Perico, N., F. Casiraghi, M. Introna, E. Gotti, et al. “Autologous Mesenchymal Stromal Cells and Kidney Transplantation: A Pilot Study of Safety and Clinical Feasibility.” Clinical Journal of the American Society of Nephrolology, v.6 (2011).
Reinders, M. E. J., J. W. de Fijter, H. Roelofs, I. M. Bajema, et al. “Autologous Bone Marrow–Derived Mesenchymal Stromal Cells for the Treatment of Allograft Rejections After Renal Transplantation: Results of a Phase I Study.” Stem Cells Translational Medicine, v.2 (2013).
Westover, A. J., D. A. Buffington, and H. D. Humes. “Enhanced Propagation of Adult Human Renal Epithelial Progenitor Cells to Improve Cell Sourcing for Tissue Engineered Therapeutic Devices for Renal Diseases.” Journal of Tissue Engineering and Regenerative Medicine, v.6 (2012).
Clinical Trials, U.S.: Multiple Sclerosis
Clinical Trials, U.S.: Multiple Sclerosis
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Clinical Trials, U.S.: Multiple Sclerosis
With the cause of the immune mediated inflammatory disease attacking myelinated axons in the central nervous system (CNS) still not known, multiple sclerosis (MS) has been under constant research for advances in treatment options and new understanding about the disease. The major areas of research over the years have been the following:
New understandings about the genetics of the disease
Understanding of how nerve cells are injured and how this injury might be prevented or reversed
More drug treatment options
New techniques to repair the damage caused by MS
New information about the potential causes of the disease
Clinical trials are conducted to collect data regarding the safety and efficacy of new drugs and therapies. Studies pass several steps and stages requiring extensive laboratory research that can involve years of experiments in animals and human cells. If the initial laboratory research is successful and approved for further research by the Food and Drug Administration (FDA), human testing of experimental drugs begins and is conducted in four phases. Several treatments are under investigation for multiple sclerosis and are anticipated to improve function, curtail attacks, or limit the progression of the underlying disease.
Research in several disease-modifying procedures and drugs is also under way, with clinical trials testing potential therapies believed to modify the natural course of the disease instead of targeting the symptoms or the recovery from relapses. Each phase in the study of new treatments is considered a separate trial and FDA approval is required for continuing into the next phase. Two key players devoted to research in MS are the National Institutes of Health (NIH) and the National Multiple Sclerosis Society in the United States.
Phase I Clinical Trials
Phase I studies are designed to determine the effects of the new treatment modality on humans, including its absorption, metabolism, excretion, and possible side effects from increased dosage levels and usually involve only a small number of healthy paid volunteers—20 to 100. This process can take several months to complete. The most notable of the ongoing Phase 1 clinical trials on MS in the United States are described as follows.
Phase I-II Clinical Trial With Autologous Bone Marrow–Derived Mesenchymal Stem Cells for the Therapy of Multiple Sclerosis. This trial is for the evaluation of the safety, feasibility, and benefits of intravenous infusion of mesenchymal cells from autologous bone marrow in patients with MS.
Sclerosis. Study designed to evaluate the safety and tolerability of intrathecal (drug injected directly into the spinal canal) administration of autologous mesenchymal stem cell–derived neural progenitor cells (MSC-NP) in patients with progressive MS.
Investigating Mechanism of Action of DAC HYP in the Treatment of High-Inflammatory Multiple Sclerosis (MS). To investigate the mechanism of action and to assess long-term safety and efficacy of CD25-blocking therapies in HI-MS.
Double Blind Placebo-Controlled Phase I/II Clinical Trial of Idebenone in Patients With Primary Progressive Multiple Sclerosis (IPPoMS). Idebenone is a drug that is similar to coenzyme Q10, a common dietary supplement. Research data suggest that idebenone may be able to limit demyelination and death of brain cells and thereby slow or halt the progression of neurological dysfunction in MS.
Comparison of the Efficacy and Mechanisms for MBCT and CT for Multiple Sclerosis (MS) Chronic Pain. Cognitive therapy (CT) and mindfulness-based cognitive therapy (MBCT) is a psychosocial treatment that has been proven to be potentially beneficial for chronic MS pain. The aim is to teach patients to identify and replace unhelpful thoughts about pain with helpful, more adaptive thoughts.
Lipoic Acid as a Treatment for Acute Optic Neuritis. Explores the hypothesis that oral lipoic acid can safely help relieve permanent optic nerve injury in patients diagnosed with acute optic neuritis. It will also help determine how the body absorbs and breaks down the study drug, and what effects it has on the immune system.
Phase II Clinical Trials
Phase
