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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.

التفاصيل البيبلوغرافية
العنوان: Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: a phase 1/2a trial.
المؤلفون: Baloh RH; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Novartis Institutes for BioMedical Research, Cambridge, MA, USA., Johnson JP; Cedars-Sinai Spine Center, Los Angeles, CA, USA., Avalos P; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Allred P; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Novartis Institutes for BioMedical Research, Cambridge, MA, USA., Svendsen S; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Gowing G; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Fujifilm Cellular Dynamics, Inc., Madison, WI, USA., Roxas K; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 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; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 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.; Fujifilm Cellular Dynamics, Inc., Madison, WI, USA., Wheeler K; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Los Angeles, CA, USA., Prina C; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Fine D; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Kendra-Romito T; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Stokes H; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Manoukian V; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Muthukumaran A; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Garcia L; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Bañuelos MG; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Godoy M; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, USA., Bresee C; Biostatistics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Yu H; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA., Drazin D; Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Department of Neurosurgery, Providence Regional Medical Center Everett, Everett, WA, USA., Ross L; Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Naruse R; Department of Anesthesiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Babu H; Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Department of Neurosurgery, SUNY-Upstate Medical University, Syracuse, NY, USA., Macklin EA; Biostatistics Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Vo A; Cedars-Sinai Comprehensive Transplant Center, Los Angeles, CA, USA., Elsayegh A; Department of Pulmonary and Critical Care, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Tourtellotte W; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Maya M; Department of Imaging, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Burford M; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Diaz F; Department of Neurology, 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 Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Svendsen CN; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Clive.svendsen@cshs.org.
المصدر: Nature medicine [Nat Med] 2022 Sep; Vol. 28 (9), pp. 1813-1822. Date of Electronic Publication: 2022 Sep 05.
نوع المنشور: Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Company Country of Publication: United States NLM ID: 9502015 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-170X (Electronic) Linking ISSN: 10788956 NLM ISO Abbreviation: Nat Med Subsets: MEDLINE
أسماء مطبوعة: Publication: New York Ny : Nature Publishing Company
Original Publication: New York, NY : Nature Pub. Co., [1995-
مواضيع طبية MeSH: Amyotrophic Lateral Sclerosis*/therapy , Neural Stem Cells*, Animals ; Disease Models, Animal ; Glial Cell Line-Derived Neurotrophic Factor/genetics ; Humans ; Spinal Cord ; Superoxide Dismutase
مستخلص: 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.
(© 2022. The Author(s).)
التعليقات: Comment in: Nat Med. 2022 Sep;28(9):1751-1752. (PMID: 36097225)
Comment in: Trends Mol Med. 2022 Nov;28(11):897-899. (PMID: 36182630)
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معلومات مُعتمدة: K26 OD010945 United States OD NIH HHS; K26 RR026099 United States RR NCRR NIH HHS; R01 NS095894 United States NS NINDS NIH HHS
سلسلة جزيئية: ClinicalTrials.gov NCT02943850
المشرفين على المادة: 0 (Glial Cell Line-Derived Neurotrophic Factor)
EC 1.15.1.1 (Superoxide Dismutase)
تواريخ الأحداث: Date Created: 20220905 Date Completed: 20220926 Latest Revision: 20221130
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC9499868
DOI: 10.1038/s41591-022-01956-3
PMID: 36064599
قاعدة البيانات: MEDLINE
الوصف
تدمد:1546-170X
DOI:10.1038/s41591-022-01956-3