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

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.

journal_name

Nat Med

journal_title

Nature medicine

authors

Romani L,Oikonomou V,Moretti S,Iannitti RG,D'Adamo MC,Villella VR,Pariano M,Sforna L,Borghi M,Bellet MM,Fallarino F,Pallotta MT,Servillo G,Ferrari E,Puccetti P,Kroemer G,Pessia M,Maiuri L,Goldstein AL,Garaci E

doi

10.1038/nm.4305

subject

Has Abstract

pub_date

2017-05-01 00:00:00

pages

590-600

issue

5

eissn

1078-8956

issn

1546-170X

pii

nm.4305

journal_volume

23

pub_type

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