SPX-101 is stable in and retains function after exposure to cystic fibrosis sputum

Autores
Sesma, Juliana; Wu, Bryant; Stuhlmiller, Timothy J.; Scott, David W.
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: In healthy lungs, epithelial sodium channel (ENaC) is regulated by short, palate, lung, and nasal clone 1 (SPLUNC1). In cystic fibrosis (CF), ENaC is hyperactivated in part due to a loss of SPLUNC1 function. We have developed SPX-101 to replace the lost function of SPLUNC1 in the CF lung. Methods: Expression of SPLUNC1 was determined in sputum from healthy and CF donors. Stability of SPLUNC1, S18 (the ENaC regulatory domain of SPLUNC1), and SPX-101 was determined in sputum from CF donors and towards neutrophil elastase. Activity of SPX-101 after exposure to CF sputum was determined in airway epithelial cells from CF donors and in the βENaC transgenic mouse model. Results: SPLUNC1 protein expression is significantly reduced in CF as compared to healthy sputum. SPLUNC1 is rapidly degraded in CF sputum as well as by a number of individual proteases known to be found in the sputum. SPX-101, but not S18, is stable in CF sputum. Finally, SPX-101 retains its ability to internalize ENaC, regulate airway surface liquid height, and increase survival of βENaC mice after exposure to CF sputum. Conclusions: Our results demonstrate that SPX-101, but not SPLUNC1 or S18, is stable in CF sputum. These results support the therapeutic development of SPX-101 for the treatment of cystic fibrosis.
Fil: Sesma, Juliana. Spyryx Biosciences; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Wu, Bryant. Spyryx Biosciences; Estados Unidos
Fil: Stuhlmiller, Timothy J.. Spyryx Biosciences; Estados Unidos
Fil: Scott, David W.. Spyryx Biosciences; Estados Unidos
Materia
AIRWAY HYDRATION
ENAC
MUCUS
SPX-101
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/96267
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/96267
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling SPX-101 is stable in and retains function after exposure to cystic fibrosis sputumSesma, JulianaWu, BryantStuhlmiller, Timothy J.Scott, David W.AIRWAY HYDRATIONENACMUCUSSPX-101https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: In healthy lungs, epithelial sodium channel (ENaC) is regulated by short, palate, lung, and nasal clone 1 (SPLUNC1). In cystic fibrosis (CF), ENaC is hyperactivated in part due to a loss of SPLUNC1 function. We have developed SPX-101 to replace the lost function of SPLUNC1 in the CF lung. Methods: Expression of SPLUNC1 was determined in sputum from healthy and CF donors. Stability of SPLUNC1, S18 (the ENaC regulatory domain of SPLUNC1), and SPX-101 was determined in sputum from CF donors and towards neutrophil elastase. Activity of SPX-101 after exposure to CF sputum was determined in airway epithelial cells from CF donors and in the βENaC transgenic mouse model. Results: SPLUNC1 protein expression is significantly reduced in CF as compared to healthy sputum. SPLUNC1 is rapidly degraded in CF sputum as well as by a number of individual proteases known to be found in the sputum. SPX-101, but not S18, is stable in CF sputum. Finally, SPX-101 retains its ability to internalize ENaC, regulate airway surface liquid height, and increase survival of βENaC mice after exposure to CF sputum. Conclusions: Our results demonstrate that SPX-101, but not SPLUNC1 or S18, is stable in CF sputum. These results support the therapeutic development of SPX-101 for the treatment of cystic fibrosis.Fil: Sesma, Juliana. Spyryx Biosciences; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wu, Bryant. Spyryx Biosciences; Estados UnidosFil: Stuhlmiller, Timothy J.. Spyryx Biosciences; Estados UnidosFil: Scott, David W.. Spyryx Biosciences; Estados UnidosElsevier Science2019-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/96267Sesma, Juliana; Wu, Bryant; Stuhlmiller, Timothy J.; Scott, David W.; SPX-101 is stable in and retains function after exposure to cystic fibrosis sputum; Elsevier Science; Journal Of Cystic Fibrosis; 18; 2; 3-2019; 244-2501569-1993CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.jcf.2018.06.002info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1569199318306271info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:49:13Zoai:ri.conicet.gov.ar:11336/96267instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:49:13.977CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv SPX-101 is stable in and retains function after exposure to cystic fibrosis sputum
title SPX-101 is stable in and retains function after exposure to cystic fibrosis sputum
spellingShingle SPX-101 is stable in and retains function after exposure to cystic fibrosis sputum
Sesma, Juliana
AIRWAY HYDRATION
ENAC
MUCUS
SPX-101
title_short SPX-101 is stable in and retains function after exposure to cystic fibrosis sputum
title_full SPX-101 is stable in and retains function after exposure to cystic fibrosis sputum
title_fullStr SPX-101 is stable in and retains function after exposure to cystic fibrosis sputum
title_full_unstemmed SPX-101 is stable in and retains function after exposure to cystic fibrosis sputum
title_sort SPX-101 is stable in and retains function after exposure to cystic fibrosis sputum
dc.creator.none.fl_str_mv Sesma, Juliana
Wu, Bryant
Stuhlmiller, Timothy J.
Scott, David W.
author Sesma, Juliana
author_facet Sesma, Juliana
Wu, Bryant
Stuhlmiller, Timothy J.
Scott, David W.
author_role author
author2 Wu, Bryant
Stuhlmiller, Timothy J.
Scott, David W.
author2_role author
author
author
dc.subject.none.fl_str_mv AIRWAY HYDRATION
ENAC
MUCUS
SPX-101
topic AIRWAY HYDRATION
ENAC
MUCUS
SPX-101
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: In healthy lungs, epithelial sodium channel (ENaC) is regulated by short, palate, lung, and nasal clone 1 (SPLUNC1). In cystic fibrosis (CF), ENaC is hyperactivated in part due to a loss of SPLUNC1 function. We have developed SPX-101 to replace the lost function of SPLUNC1 in the CF lung. Methods: Expression of SPLUNC1 was determined in sputum from healthy and CF donors. Stability of SPLUNC1, S18 (the ENaC regulatory domain of SPLUNC1), and SPX-101 was determined in sputum from CF donors and towards neutrophil elastase. Activity of SPX-101 after exposure to CF sputum was determined in airway epithelial cells from CF donors and in the βENaC transgenic mouse model. Results: SPLUNC1 protein expression is significantly reduced in CF as compared to healthy sputum. SPLUNC1 is rapidly degraded in CF sputum as well as by a number of individual proteases known to be found in the sputum. SPX-101, but not S18, is stable in CF sputum. Finally, SPX-101 retains its ability to internalize ENaC, regulate airway surface liquid height, and increase survival of βENaC mice after exposure to CF sputum. Conclusions: Our results demonstrate that SPX-101, but not SPLUNC1 or S18, is stable in CF sputum. These results support the therapeutic development of SPX-101 for the treatment of cystic fibrosis.
Fil: Sesma, Juliana. Spyryx Biosciences; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Wu, Bryant. Spyryx Biosciences; Estados Unidos
Fil: Stuhlmiller, Timothy J.. Spyryx Biosciences; Estados Unidos
Fil: Scott, David W.. Spyryx Biosciences; Estados Unidos
description Background: In healthy lungs, epithelial sodium channel (ENaC) is regulated by short, palate, lung, and nasal clone 1 (SPLUNC1). In cystic fibrosis (CF), ENaC is hyperactivated in part due to a loss of SPLUNC1 function. We have developed SPX-101 to replace the lost function of SPLUNC1 in the CF lung. Methods: Expression of SPLUNC1 was determined in sputum from healthy and CF donors. Stability of SPLUNC1, S18 (the ENaC regulatory domain of SPLUNC1), and SPX-101 was determined in sputum from CF donors and towards neutrophil elastase. Activity of SPX-101 after exposure to CF sputum was determined in airway epithelial cells from CF donors and in the βENaC transgenic mouse model. Results: SPLUNC1 protein expression is significantly reduced in CF as compared to healthy sputum. SPLUNC1 is rapidly degraded in CF sputum as well as by a number of individual proteases known to be found in the sputum. SPX-101, but not S18, is stable in CF sputum. Finally, SPX-101 retains its ability to internalize ENaC, regulate airway surface liquid height, and increase survival of βENaC mice after exposure to CF sputum. Conclusions: Our results demonstrate that SPX-101, but not SPLUNC1 or S18, is stable in CF sputum. These results support the therapeutic development of SPX-101 for the treatment of cystic fibrosis.
publishDate 2019
dc.date.none.fl_str_mv 2019-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/96267
Sesma, Juliana; Wu, Bryant; Stuhlmiller, Timothy J.; Scott, David W.; SPX-101 is stable in and retains function after exposure to cystic fibrosis sputum; Elsevier Science; Journal Of Cystic Fibrosis; 18; 2; 3-2019; 244-250
1569-1993
CONICET Digital
CONICET
url http://hdl.handle.net/11336/96267
identifier_str_mv Sesma, Juliana; Wu, Bryant; Stuhlmiller, Timothy J.; Scott, David W.; SPX-101 is stable in and retains function after exposure to cystic fibrosis sputum; Elsevier Science; Journal Of Cystic Fibrosis; 18; 2; 3-2019; 244-250
1569-1993
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jcf.2018.06.002
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1569199318306271
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844613525751726080
score 13.070432

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