An in vitro and in vivo efficacy evaluation of gene therapy candidate SBT101 in mouse models of adrenomyeloneuropathy and in NHPs
Adrenomyeloneuropathy; Gene therapy; Neurodegenerative disease
| Autores: | , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:11351/12352 |
| Acceso en línea: | https://hdl.handle.net/11351/12352 http://hdl.handle.net/11351/12352 |
| Access Level: | acceso abierto |
| Palabra clave: | Adrenoleucodistròfia - Tractament Adrenoleucodistròfia - Aspectes genètics Rates (Animals de laboratori) Teràpia genètica DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Brain Diseases, Metabolic::Brain Diseases, Metabolic, Inborn::Adrenoleukodystrophy Other subheadings::Other subheadings::/therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Biological Therapy::Genetic Therapy ORGANISMS::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades cerebrales metabólicas::enfermedades cerebrales metabólicas congénitas::adrenoleucodistrofia Otros calificadores::Otros calificadores::/terapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapia biológica::terapia genética ORGANISMOS::Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratones |
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| dc.title.none.fl_str_mv |
An in vitro and in vivo efficacy evaluation of gene therapy candidate SBT101 in mouse models of adrenomyeloneuropathy and in NHPs |
| title |
An in vitro and in vivo efficacy evaluation of gene therapy candidate SBT101 in mouse models of adrenomyeloneuropathy and in NHPs |
| spellingShingle |
An in vitro and in vivo efficacy evaluation of gene therapy candidate SBT101 in mouse models of adrenomyeloneuropathy and in NHPs Vasireddy, Vidyullatha Adrenoleucodistròfia - Tractament Adrenoleucodistròfia - Aspectes genètics Rates (Animals de laboratori) Teràpia genètica DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Brain Diseases, Metabolic::Brain Diseases, Metabolic, Inborn::Adrenoleukodystrophy Other subheadings::Other subheadings::/therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Biological Therapy::Genetic Therapy ORGANISMS::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades cerebrales metabólicas::enfermedades cerebrales metabólicas congénitas::adrenoleucodistrofia Otros calificadores::Otros calificadores::/terapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapia biológica::terapia genética ORGANISMOS::Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratones |
| title_short |
An in vitro and in vivo efficacy evaluation of gene therapy candidate SBT101 in mouse models of adrenomyeloneuropathy and in NHPs |
| title_full |
An in vitro and in vivo efficacy evaluation of gene therapy candidate SBT101 in mouse models of adrenomyeloneuropathy and in NHPs |
| title_fullStr |
An in vitro and in vivo efficacy evaluation of gene therapy candidate SBT101 in mouse models of adrenomyeloneuropathy and in NHPs |
| title_full_unstemmed |
An in vitro and in vivo efficacy evaluation of gene therapy candidate SBT101 in mouse models of adrenomyeloneuropathy and in NHPs |
| title_sort |
An in vitro and in vivo efficacy evaluation of gene therapy candidate SBT101 in mouse models of adrenomyeloneuropathy and in NHPs |
| dc.creator.none.fl_str_mv |
Vasireddy, Vidyullatha Maguire, Casey A. Anderson, David W. Ng, Carrie Gong, Yi Eichler, Florian Onieva Salgado, Andrea Leal Julià, Marc Verdés-Franquesa, Sergi Bosch, Assumpció Sánchez Osuna, Ángela |
| author |
Vasireddy, Vidyullatha |
| author_facet |
Vasireddy, Vidyullatha Maguire, Casey A. Anderson, David W. Ng, Carrie Gong, Yi Eichler, Florian Onieva Salgado, Andrea Leal Julià, Marc Verdés-Franquesa, Sergi Bosch, Assumpció Sánchez Osuna, Ángela |
| author_role |
author |
| author2 |
Maguire, Casey A. Anderson, David W. Ng, Carrie Gong, Yi Eichler, Florian Onieva Salgado, Andrea Leal Julià, Marc Verdés-Franquesa, Sergi Bosch, Assumpció Sánchez Osuna, Ángela |
| author2_role |
author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Institut Català de la Salut [Vasireddy V, Anderson DW] SwanBio Therapeutics, Inc., Philadelphia, PA, USA. Code Bio, Lower Gwynedd, PA USA. [Maguire CA, Ng C, Gong Y, Eichler F] Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA. Harvard Medical School, Boston, MA, USA. [Onieva A, Sanchez A, Leal-Julià M, Verdés S] Departament de Bioquímica i Biologia Molecular, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain. Unitat Mixta UAB-VHIR, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Bosch A] Departament de Bioquímica i Biologia Molecular, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain. Unitat Mixta UAB-VHIR, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III (ISCIII), Madrid, Spain Vall d'Hebron Barcelona Hospital Campus |
| dc.subject.none.fl_str_mv |
Adrenoleucodistròfia - Tractament Adrenoleucodistròfia - Aspectes genètics Rates (Animals de laboratori) Teràpia genètica DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Brain Diseases, Metabolic::Brain Diseases, Metabolic, Inborn::Adrenoleukodystrophy Other subheadings::Other subheadings::/therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Biological Therapy::Genetic Therapy ORGANISMS::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades cerebrales metabólicas::enfermedades cerebrales metabólicas congénitas::adrenoleucodistrofia Otros calificadores::Otros calificadores::/terapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapia biológica::terapia genética ORGANISMOS::Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratones |
| topic |
Adrenoleucodistròfia - Tractament Adrenoleucodistròfia - Aspectes genètics Rates (Animals de laboratori) Teràpia genètica DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Brain Diseases, Metabolic::Brain Diseases, Metabolic, Inborn::Adrenoleukodystrophy Other subheadings::Other subheadings::/therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Biological Therapy::Genetic Therapy ORGANISMS::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades cerebrales metabólicas::enfermedades cerebrales metabólicas congénitas::adrenoleucodistrofia Otros calificadores::Otros calificadores::/terapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapia biológica::terapia genética ORGANISMOS::Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratones |
| description |
Adrenomyeloneuropathy; Gene therapy; Neurodegenerative disease |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2024 2024 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/11351/12352 http://hdl.handle.net/11351/12352 |
| url |
https://hdl.handle.net/11351/12352 http://hdl.handle.net/11351/12352 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Molecular Therapy - Methods & Clinical Development;32(4) https://doi.org/10.1016/j.omtm.2024.101354 |
| dc.rights.none.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
| publisher.none.fl_str_mv |
Elsevier |
| dc.source.none.fl_str_mv |
Scientia reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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1869408743697940480 |
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An in vitro and in vivo efficacy evaluation of gene therapy candidate SBT101 in mouse models of adrenomyeloneuropathy and in NHPsVasireddy, VidyullathaMaguire, Casey A.Anderson, David W.Ng, CarrieGong, YiEichler, FlorianOnieva Salgado, AndreaLeal Julià, MarcVerdés-Franquesa, SergiBosch, AssumpcióSánchez Osuna, ÁngelaAdrenoleucodistròfia - TractamentAdrenoleucodistròfia - Aspectes genèticsRates (Animals de laboratori)Teràpia genèticaDISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Brain Diseases, Metabolic::Brain Diseases, Metabolic, Inborn::AdrenoleukodystrophyOther subheadings::Other subheadings::/therapyANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Biological Therapy::Genetic TherapyORGANISMS::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::MiceENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades cerebrales metabólicas::enfermedades cerebrales metabólicas congénitas::adrenoleucodistrofiaOtros calificadores::Otros calificadores::/terapiaTÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapia biológica::terapia genéticaORGANISMOS::Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratonesAdrenomyeloneuropathy; Gene therapy; Neurodegenerative diseaseAdrenomieloneuropatía; Terapia génica; Enfermedad neurodegenerativaAdrenomieloneuropatia; Teràpia gènica; Malaltia neurodegenerativaAdrenomyeloneuropathy is a progressive neurodegenerative disease caused by pathogenic variants in the ABCD1 gene, resulting in very-long-chain fatty acid (VLCFA) accumulation that leads to dying-back axonopathy. Our candidate gene therapy, SBT101 (AAV9-human ABCD1 [hABCD1]), aims to ameliorate pathology by delivering functional copies of hABCD1 to the spinal cord. Transduced cells produce functional ABCD1 protein, thereby repairing the underlying biochemical defect. In vitro and in vivo mouse studies were conducted to assess the biochemical and functional efficacy of SBT101 and show effective delivery to target tissues involved in the disease pathology: spinal cord and dorsal root ganglia. Administration of SBT101 to mixed glial cell cultures from Abcd1-Null mice, and to male Abcd1 knockout (Abcd1−/y) and double-knockout (Abcd1−/y/Abcd2−/−) mice led to increased hABCD1 production and reduced VLCFA. Double-knockout mice also exhibited improved grip strength. Furthermore, we conducted biodistribution and safety assessments in nonhuman primates. Six-hour intrathecal lumbar infusions demonstrated effective transduction throughout target tissues, supporting the clinical feasibility of the procedure. SBT101 was well tolerated, with no observed SBT101-related mortality or clinical signs. These findings not only provide preclinical efficacy data for SBT101 but also inform clinically relevant SBT101 dose selection for patients with adrenomyeloneuropathy.The studies were funded by SwanBio Therapeutic Ltd. The authors thank Eileen Sawyer for reviewing the manuscript and Dr. Javier del Rey for providing viral genome quantification and mRNA analysis in the DKO mouse in vivo study. The authors also thank Dr. David Gothard and Dr. Kirsty Walters of Oxford PharmaGenesis, Oxford, UK for providing medical writing support, which was sponsored by SwanBio in accordance with Good Publication Practice guidelines (GPP 2022).ElsevierInstitut Català de la Salut[Vasireddy V, Anderson DW] SwanBio Therapeutics, Inc., Philadelphia, PA, USA. Code Bio, Lower Gwynedd, PA USA. [Maguire CA, Ng C, Gong Y, Eichler F] Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA. Harvard Medical School, Boston, MA, USA. [Onieva A, Sanchez A, Leal-Julià M, Verdés S] Departament de Bioquímica i Biologia Molecular, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain. Unitat Mixta UAB-VHIR, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Bosch A] Departament de Bioquímica i Biologia Molecular, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain. Unitat Mixta UAB-VHIR, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III (ISCIII), Madrid, SpainVall d'Hebron Barcelona Hospital Campus202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11351/12352http://hdl.handle.net/11351/12352Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésMolecular Therapy - Methods & Clinical Development;32(4)https://doi.org/10.1016/j.omtm.2024.101354Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/123522026-05-29T05:05:01Z |
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