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Health outcomes in spinal muscular atrophy type 1 following AVXS‐101 gene replacement therapy

BACKGROUND: Spinal Muscular Atrophy type 1 (SMA1) is a rare genetic neuromuscular disease where 75% of SMA1 patients die/require permanent‐ventilation by 13.6 months. This study assessed the health outcomes of SMA1 infants treated with AVXS‐101 gene replacement therapy. METHODS: Twelve genetically c...

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Autores principales: Al‐Zaidy, Samiah, Pickard, A. Simon, Kotha, Kavitha, Alfano, Lindsay N., Lowes, Linda, Paul, Grace, Church, Kathleen, Lehman, Kelly, Sproule, Douglas M., Dabbous, Omar, Maru, Benit, Berry, Katherine, Arnold, W. David, Kissel, John T., Mendell, Jerry R., Shell, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590370/
https://www.ncbi.nlm.nih.gov/pubmed/30548438
http://dx.doi.org/10.1002/ppul.24203
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author Al‐Zaidy, Samiah
Pickard, A. Simon
Kotha, Kavitha
Alfano, Lindsay N.
Lowes, Linda
Paul, Grace
Church, Kathleen
Lehman, Kelly
Sproule, Douglas M.
Dabbous, Omar
Maru, Benit
Berry, Katherine
Arnold, W. David
Kissel, John T.
Mendell, Jerry R.
Shell, Richard
author_facet Al‐Zaidy, Samiah
Pickard, A. Simon
Kotha, Kavitha
Alfano, Lindsay N.
Lowes, Linda
Paul, Grace
Church, Kathleen
Lehman, Kelly
Sproule, Douglas M.
Dabbous, Omar
Maru, Benit
Berry, Katherine
Arnold, W. David
Kissel, John T.
Mendell, Jerry R.
Shell, Richard
author_sort Al‐Zaidy, Samiah
collection PubMed
description BACKGROUND: Spinal Muscular Atrophy type 1 (SMA1) is a rare genetic neuromuscular disease where 75% of SMA1 patients die/require permanent‐ventilation by 13.6 months. This study assessed the health outcomes of SMA1 infants treated with AVXS‐101 gene replacement therapy. METHODS: Twelve genetically confirmed SMA1 infants with homozygous deletions of the SMN1 gene and two SMN2 gene copies received a one‐time intravenous proposed therapeutic dose of AVXS‐101 in an open label study conducted between December 2014 and 2017. Patients were followed for 2‐years post‐treatment for outcomes including (1) pulmonary interventions; (2) nutritional interventions; (3) swallow function; (4) hospitalization rates; and (5) motor function. RESULTS: All 12 patients completed the study. Seven infants did not require noninvasive ventilation (NIV) by study completion. Eleven patients had stable or improved swallow function, demonstrated by the ability to feed orally; 11 patients were able to speak. The mean proportion of time hospitalized was 4.4%; the mean unadjusted annualized hospitalization rate was 2.1 (range = 0, 7.6), with a mean length of stay/hospitalization of 6.7 (range = 3, 12.1) days. Eleven patients achieved full head control and sitting unassisted and two patients were walking independently. CONCLUSIONS: AVXS‐101 treatment in SMA1 was associated with reduced pulmonary and nutritional support requirements, improved motor function, and decreased hospitalization rate over the follow‐up period. This contrasts with the natural history of progressive respiratory failure and reduced survival. The reduced healthcare utilization could potentially alleviate patient and caregiver burden, suggesting an overall improved quality of life following gene replacement therapy. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT02122952.
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spelling pubmed-65903702019-07-08 Health outcomes in spinal muscular atrophy type 1 following AVXS‐101 gene replacement therapy Al‐Zaidy, Samiah Pickard, A. Simon Kotha, Kavitha Alfano, Lindsay N. Lowes, Linda Paul, Grace Church, Kathleen Lehman, Kelly Sproule, Douglas M. Dabbous, Omar Maru, Benit Berry, Katherine Arnold, W. David Kissel, John T. Mendell, Jerry R. Shell, Richard Pediatr Pulmonol Original Articles BACKGROUND: Spinal Muscular Atrophy type 1 (SMA1) is a rare genetic neuromuscular disease where 75% of SMA1 patients die/require permanent‐ventilation by 13.6 months. This study assessed the health outcomes of SMA1 infants treated with AVXS‐101 gene replacement therapy. METHODS: Twelve genetically confirmed SMA1 infants with homozygous deletions of the SMN1 gene and two SMN2 gene copies received a one‐time intravenous proposed therapeutic dose of AVXS‐101 in an open label study conducted between December 2014 and 2017. Patients were followed for 2‐years post‐treatment for outcomes including (1) pulmonary interventions; (2) nutritional interventions; (3) swallow function; (4) hospitalization rates; and (5) motor function. RESULTS: All 12 patients completed the study. Seven infants did not require noninvasive ventilation (NIV) by study completion. Eleven patients had stable or improved swallow function, demonstrated by the ability to feed orally; 11 patients were able to speak. The mean proportion of time hospitalized was 4.4%; the mean unadjusted annualized hospitalization rate was 2.1 (range = 0, 7.6), with a mean length of stay/hospitalization of 6.7 (range = 3, 12.1) days. Eleven patients achieved full head control and sitting unassisted and two patients were walking independently. CONCLUSIONS: AVXS‐101 treatment in SMA1 was associated with reduced pulmonary and nutritional support requirements, improved motor function, and decreased hospitalization rate over the follow‐up period. This contrasts with the natural history of progressive respiratory failure and reduced survival. The reduced healthcare utilization could potentially alleviate patient and caregiver burden, suggesting an overall improved quality of life following gene replacement therapy. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT02122952. John Wiley and Sons Inc. 2018-12-12 2019-02 /pmc/articles/PMC6590370/ /pubmed/30548438 http://dx.doi.org/10.1002/ppul.24203 Text en © 2018 The Authors. Pediatric Pulmonology Published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Al‐Zaidy, Samiah
Pickard, A. Simon
Kotha, Kavitha
Alfano, Lindsay N.
Lowes, Linda
Paul, Grace
Church, Kathleen
Lehman, Kelly
Sproule, Douglas M.
Dabbous, Omar
Maru, Benit
Berry, Katherine
Arnold, W. David
Kissel, John T.
Mendell, Jerry R.
Shell, Richard
Health outcomes in spinal muscular atrophy type 1 following AVXS‐101 gene replacement therapy
title Health outcomes in spinal muscular atrophy type 1 following AVXS‐101 gene replacement therapy
title_full Health outcomes in spinal muscular atrophy type 1 following AVXS‐101 gene replacement therapy
title_fullStr Health outcomes in spinal muscular atrophy type 1 following AVXS‐101 gene replacement therapy
title_full_unstemmed Health outcomes in spinal muscular atrophy type 1 following AVXS‐101 gene replacement therapy
title_short Health outcomes in spinal muscular atrophy type 1 following AVXS‐101 gene replacement therapy
title_sort health outcomes in spinal muscular atrophy type 1 following avxs‐101 gene replacement therapy
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590370/
https://www.ncbi.nlm.nih.gov/pubmed/30548438
http://dx.doi.org/10.1002/ppul.24203
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