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Nat Med. 2017 May;23(5):590-600. doi: 10.1038/nm.4305. Epub 2017 Apr 10.

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

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Department of Experimental Medicine, University of Perugia, Perugia, Italy.
Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta.
European Institute for Research in Cystic Fibrosis, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
Centre de Recherche des Cordeliers, INSERM U1138, Université Paris Descartes, Paris, France.
Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France.
Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.
Department of Health Sciences, University of Piemonte Orientale, Novara, Italy.
Department of Biochemistry and Molecular Medicine, George Washington University, School of Medicine and Health Sciences, Washington, DC, USA.
University San Raffaele and IRCCS San Raffaele, Rome, Italy.


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.

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