Journal
CURRENT OPINION IN NEUROLOGY
Volume 31, Issue 5, Pages 655-661Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/WCO.0000000000000598
Keywords
amyotrophic lateral sclerosis; mesenchymal stem cells; neural progenitor cells; regulatory T-cells
Categories
Funding
- NIH/NINDS [NS097545]
- Muscular Dystrophy Association [352536]
- NIH/NIA [P50AG02568]
- California Institute for Regenerative Medicine [CLIN2-09284]
- Department of Defense [W81XWH-14-1-0189]
- NIH [1UG3NS105703, U54NS091046-01]
- ALS Association [18-SI-389]
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Purpose of review This review analyses the recent efforts to develop therapeutics using transplantation of stem cells for amyotrophic lateral sclerosis (ALS). Recent findings Stem cells are considered as a potential therapeutic for a variety of neurodegenerative diseases, in an effort to either replace cells that are lost, or to enhance the survival of the remaining cells. In ALS, meaningful attempts to verify the safety and feasibility of many cell transplantation approaches have only recently been completed or are underway. Due to the complexities of reconstructing complete motor neuron circuits in adult patients, current approaches aim rather to prolong the survival and function of existing motor neurons through paracrine effects or production of new interneurons or astrocytes. Recent trials showed that autologous mesenchymal stem cells can be safely injected intrathecally, transiently enhancing growth factor concentrations and anti-inflammatory cytokines into the cerebrospinal fluid. Likewise, a small pilot study investigating safety of autologous transplantation of regulatory T-cells for immunomodulation was recently completed. Finally, early phase trials demonstrated safety of direct surgical transplantation of heterologous fetal-derived neural progenitor cells into the spinal cord of ALS patients, as an attempt to provide a lasting source of local trophic support for motor neurons. Summary With clinical trials recently demonstrating that stem cell transplantation can be safe and well tolerated in ALS, the field is positioned to complete pivotal controlled trials to determine efficacy.
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