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

Luigina Romani, Vasilis Oikonomou, Silvia Moretti, Rossana G. Iannitti, Maria Cristina D'Adamo, Valeria R. Villella, Marilena Pariano, Luigi Sforna, Monica Borghi, Marina M. Bellet, Francesca Fallarino, Maria Teresa Pallotta, Giuseppe Servillo, Eleonora Ferrari, Paolo Puccetti, Guido Kroemer, Mauro Pessia, Luigi Maiuri, Allan L. Goldstein, Enrico Garaci

Research output: Contribution to journalArticle

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 (Tα1) - 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. Tα1 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, Tα1 has strong potential to be an efficacious single-molecule-based therapeutic agent for CF.

Original languageEnglish
Pages (from-to)590-600
Number of pages11
JournalNature Medicine
Volume23
Issue number5
DOIs
Publication statusPublished - May 1 2017

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Romani, L., Oikonomou, V., Moretti, S., Iannitti, R. G., D'Adamo, M. C., Villella, V. R., Pariano, M., Sforna, L., Borghi, M., Bellet, M. M., Fallarino, F., Pallotta, M. T., Servillo, G., Ferrari, E., Puccetti, P., Kroemer, G., Pessia, M., Maiuri, L., Goldstein, A. L., & Garaci, E. (2017). Thymosin α1 represents a potential potent single-molecule-based therapy for cystic fibrosis. Nature Medicine, 23(5), 590-600. https://doi.org/10.1038/nm.4305