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Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: a phase 1/2a trial.
Baloh, Robert H; Johnson, J Patrick; Avalos, Pablo; Allred, Peggy; Svendsen, Soshana; Gowing, Genevieve; Roxas, Kristina; Wu, Amanda; Donahue, Becky; Osborne, Sheryl; Lawless, George; Shelley, Brandon; Wheeler, Koral; Prina, Carolyn; Fine, Dana; Kendra-Romito, Tami; Stokes, Haniah; Manoukian, Vicki; Muthukumaran, Abirami; Garcia, Leslie; Bañuelos, Maria G; Godoy, Marlesa; Bresee, Catherine; Yu, Hong; Drazin, Doniel; Ross, Lindsey; Naruse, Robert; Babu, Harish; Macklin, Eric A; Vo, Ashley; Elsayegh, Ashraf; Tourtellotte, Warren; Maya, Marcel; Burford, Matthew; Diaz, Frank; Patil, Chirag G; Lewis, Richard A; Svendsen, Clive N.
Afiliação
  • Baloh RH; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Johnson JP; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Avalos P; Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
  • Allred P; Cedars-Sinai Spine Center, Los Angeles, CA, USA.
  • Svendsen S; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Gowing G; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Roxas K; Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
  • Wu A; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Donahue B; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Osborne S; Fujifilm Cellular Dynamics, Inc., Madison, WI, USA.
  • Lawless G; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Shelley B; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Wheeler K; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Prina C; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Fine D; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Kendra-Romito T; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Stokes H; Fujifilm Cellular Dynamics, Inc., Madison, WI, USA.
  • Manoukian V; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Muthukumaran A; USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Los Angeles, CA, USA.
  • Garcia L; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Bañuelos MG; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Godoy M; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Bresee C; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Yu H; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Drazin D; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Ross L; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Naruse R; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Babu H; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Macklin EA; Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, USA.
  • Vo A; Biostatistics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Elsayegh A; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
  • Tourtellotte W; Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Maya M; Department of Neurosurgery, Providence Regional Medical Center Everett, Everett, WA, USA.
  • Burford M; Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Diaz F; Department of Anesthesiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Patil CG; Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Lewis RA; Department of Neurosurgery, SUNY-Upstate Medical University, Syracuse, NY, USA.
  • Svendsen CN; Biostatistics Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Nat Med ; 28(9): 1813-1822, 2022 09.
Article em En | MEDLINE | ID: mdl-36064599
ABSTRACT
Amyotrophic lateral sclerosis (ALS) involves progressive motor neuron loss, leading to paralysis and death typically within 3-5 years of diagnosis. Dysfunctional astrocytes may contribute to disease and glial cell line-derived neurotrophic factor (GDNF) can be protective. Here we show that human neural progenitor cells transduced with GDNF (CNS10-NPC-GDNF) differentiated to astrocytes protected spinal motor neurons and were safe in animal models. CNS10-NPC-GDNF were transplanted unilaterally into the lumbar spinal cord of 18 ALS participants in a phase 1/2a study (NCT02943850). The primary endpoint of safety at 1 year was met, with no negative effect of the transplant on motor function in the treated leg compared with the untreated leg. Tissue analysis of 13 participants who died of disease progression showed graft survival and GDNF production. Benign neuromas near delivery sites were common incidental findings at post-mortem. This study shows that one administration of engineered neural progenitors can provide new support cells and GDNF delivery to the ALS patient spinal cord for up to 42 months post-transplantation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Neurais / Esclerose Lateral Amiotrófica Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Nat Med Assunto da revista: BIOLOGIA MOLECULAR / MEDICINA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Neurais / Esclerose Lateral Amiotrófica Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Nat Med Assunto da revista: BIOLOGIA MOLECULAR / MEDICINA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos