Robert H Baloh1,2, Jonathan D Glass3, Clive N Svendsen2. 1. Department of Neurology, Center for Neural Science and Medicine. 2. Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California. 3. Emory University School of Medicine, Atlanta, Georgia, USA.
Abstract
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.
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 ALSpatients, 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.
Authors: Robert H Baloh; J Patrick Johnson; Pablo Avalos; Peggy Allred; Soshana Svendsen; Genevieve Gowing; Kristina Roxas; Amanda Wu; Becky Donahue; Sheryl Osborne; George Lawless; Brandon Shelley; Koral Wheeler; Carolyn Prina; Dana Fine; Tami Kendra-Romito; Haniah Stokes; Vicki Manoukian; Abirami Muthukumaran; Leslie Garcia; Maria G Bañuelos; Marlesa Godoy; Catherine Bresee; Hong Yu; Doniel Drazin; Lindsey Ross; Robert Naruse; Harish Babu; Eric A Macklin; Ashley Vo; Ashraf Elsayegh; Warren Tourtellotte; Marcel Maya; Matthew Burford; Frank Diaz; Chirag G Patil; Richard A Lewis; Clive N Svendsen Journal: Nat Med Date: 2022-09-05 Impact factor: 87.241
Authors: Amirali Toossi; Bradley Bergin; Maedeh Marefatallah; Behdad Parhizi; Neil Tyreman; Dirk G Everaert; Sabereh Rezaei; Peter Seres; J Christopher Gatenby; Steve I Perlmutter; Vivian K Mushahwar Journal: Sci Rep Date: 2021-01-21 Impact factor: 4.379