Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) that compromise its chloride channel activity. The most common mutation, p.Phe508del, results in the production of a misfolded CFTR protein, which has residual channel activity but is prematurely degraded. Because of the inherent complexity of the pathogenetic mechanisms involved in CF, which include impaired chloride permeability and persistent lung inflammation, a multidrug approach is required for efficacious CF therapy. To date, no individual drug with pleiotropic beneficial effects is available for CF. Here we report on the ability of thymosin alpha 1 (T alpha 1)-a naturally occurring polypeptide with an excellent safety profile in the clinic when used as an adjuvant or an immunotherapeutic agent- to rectify the multiple tissue defects in mice with CF as well as in cells from subjects with the p.Phe508del mutation. T alpha 1 displayed two combined properties that favorably opposed CF symptomatology: it reduced inflammation and increased CFTR maturation, stability and activity. By virtue of this two-pronged action, T alpha 1 has strong potential to be an efficacious single-molecule-based therapeutic agent for CF.

Thymosin α1 represents a potential potent single-molecule-based therapy for cystic fibrosis

Romani, Luigina;Oikonomou, Vasilis;Moretti, Silvia;Iannitti, Rossana G;D'Adamo, Maria Cristina;Pariano, Marilena;Sforna, Luigi;Borghi, Monica;Bellet, Marina M;Fallarino, Francesca;Pallotta, Maria Teresa;Servillo, Giuseppe;Puccetti, Paolo;Pessia, Mauro;
2017-01-01

Abstract

Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) that compromise its chloride channel activity. The most common mutation, p.Phe508del, results in the production of a misfolded CFTR protein, which has residual channel activity but is prematurely degraded. Because of the inherent complexity of the pathogenetic mechanisms involved in CF, which include impaired chloride permeability and persistent lung inflammation, a multidrug approach is required for efficacious CF therapy. To date, no individual drug with pleiotropic beneficial effects is available for CF. Here we report on the ability of thymosin alpha 1 (T alpha 1)-a naturally occurring polypeptide with an excellent safety profile in the clinic when used as an adjuvant or an immunotherapeutic agent- to rectify the multiple tissue defects in mice with CF as well as in cells from subjects with the p.Phe508del mutation. T alpha 1 displayed two combined properties that favorably opposed CF symptomatology: it reduced inflammation and increased CFTR maturation, stability and activity. By virtue of this two-pronged action, T alpha 1 has strong potential to be an efficacious single-molecule-based therapeutic agent for CF.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11391/1538954
Citazioni
  • ???jsp.display-item.citation.pmc??? 54
  • Scopus 79
  • ???jsp.display-item.citation.isi??? 80
social impact