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
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/96267
Ver los metadatos del registro completo
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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 Técnicas2025-10-22T11:18:39Zoai: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:34982025-10-22 11:18:39.895CONICET 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 |
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article |
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publishedVersion |
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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 |
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eng |
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eng |
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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 |
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info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
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openAccess |
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https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
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Elsevier Science |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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