Unmet needs in cystic fibrosis

Abstract

Cystic fibrosis (CF) is a multisystem illness caused by abnormalities in the CF transmembrane conductance regulator (CFTR) gene and protein. CFTR is an ion channel regulating transport of chloride, bicarbonate, and water, and influencing sodium resorption. It is inherited as an autosomal recessive disorder, and with about 70,000 CF patients worldwide, it is the most common life shortening disease among persons of European descent. CFTR disease-causing mutations have been organized into six classes. : Recently, small molecule targeted therapy for specific classes of CFTR abnormalities have included CFTR correctors that decrease protein degradation and CFTR potentiators that increase channel open probability enhancing chloride transport. Although there are many novel medications in preclinical and clinical testing, there is need for safe and effective CFTR modulating drugs and immunomodulatory medications to decrease the abundant neutrophilic inflammation response in the airway without unwanted adverse effects. Thymosin alpha 1 treatment of airway cells isolated from phe508del CF patients and from CF knockout mice, decreased inflammation, increased CFTR maturation, and facilitated translocation of CFTR protein to the plasma membrane increasing channel activity. If similar results are seen in humans with CF, thymosin alpha 1 has the unique potential to be a single molecule therapy for treating CF airway disease.