Universität zu Köln

van Koningsbruggen-Rietschel, Silke (2019). Novel treatment modalities for cystic fibrosis. Pneumologe, 16 (2). S. 88 - 98. HEIDELBERG: SPRINGER HEIDELBERG. ISSN 1613-6055

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Abstract

Cystic fibrosis (CF) is the most frequent life-shortening genetic disorder with an incidence of approximately 1:3300. The development of new treatment options is moving rapidly forward and looks very promising. Besides new modalities for symptomatic treatments, curative treatment approaches are also being developed. Pharmacological approaches to treat the basic defect of CF have become reality and several cystic fibrosis transmembrane conductance regulator (CFTR) modulators have already been licensed for specific mutations. The potentiator ivacaftor, which improves channel activity of CFTR has proven to be effective, although not fully corrective, in classIII mutations. The combination treatment of acorrector (lumacaftor and tezacaftor), which improves cell-surface expression rate of CFTR in F508del mutations, in combination with apotentiator (ivacaftor) leads to amodestly efficacious corrective treatment in patients homozygous for F508del. Triple combinations of two correctors and one potentiator lead to restoration of CFTR function close to levels resembling acure for CF in patients carrying at least one F508del mutation. In addition to the development of mutation-specific treatment, so-called mutation-agnostic approaches are also being developed. These are corrective treatments independent of the mutation class and therefore applicable to all CF patients, e.g. gene therapy, CRISPR-CAS9 and bypass approaches such as activation of alternative chloride channels and epithelial sodium channel (ENaC) blockers. This report provides an overview of the basic defect in CF, major approaches of preclinical research, clinical trials exploring the efficacy of several CFTR modulators as mutation-specific treatment options, new developments in symptomatic treatment options as well as personalized medicine to predict treatment responses.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code van Koningsbruggen-Rietschel, Silke UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-155769
DOI:	10.1007/s10405-018-0220-8
Journal or Publication Title:	Pneumologe
Volume:	16
Number:	2
Page Range:	S. 88 - 98
Date:	2019
Publisher:	SPRINGER HEIDELBERG
Place of Publication:	HEIDELBERG
ISSN:	1613-6055
Language:	German
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TEZACAFTOR-IVACAFTOR; DOUBLE-BLIND; CFTR; PHARMACOKINETICS; LUMACAFTOR; ATALUREN; SAFETY; TRIAL Multiple languages Respiratory System Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15576