CFTR Modulator Treatment in Children<12 Years of Age – Status Quo and Challenges

Abstract

Cystic fibrosis (CF) is a genetic disease that results from mutations in the CFTR gene. It primarily affects the lungs and digestive system. Recent advancements in the treatment of CF have been driven by highly effective therapies that modulate the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which target the underlying molecular defects in CFTR function. These modulators have been demonstrated to significantly improve lung function, weight gain, and quality of life for 90% of individuals with CF, particularly those with the F508del mutation. HEMT has also demonstrated potential benefits for pancreatic and liver function, and its early use in young children may delay or prevent disease progression. However, challenges remain in optimizing biomarkers and outcome measures for younger children, addressing side effects, and developing novel therapies for mutations not responsive to current treatments. This review focuses on the efficacy, safety, and future perspectives of HEMT in children under 12 years of age, emphasizing the importance of early intervention to improve long-term outcomes in CF patients.

Zusammenfassung

Mukoviszidose (CF) ist die häufigste genetisch bedingte Stoffwechselerkrankung durch Mutationen im CFTR-Gen. Sie betrifft insbesondere die Lunge und das Verdauungssystem. Die jüngsten Fortschritte in der Behandlung der CF sind das Resultat von hochwirksamen Therapien (HEMT), welche die Funktion des CFTR-Proteins (Cystic Fibrosis Transmembrane Conductance Regulator) modulieren und damit eine kausale Therapie ermöglichen. Diese führt nachweislich zu einer Verbesserung der Lungenfunktion und Gewichtszunahme, sowie einer Steigerung der Lebensqualität bei 90% der Menschen mit Mukoviszidose, insbesondere bei denen, die mindestens eine F508del-Mutation aufweisen. Zusätzlich besteht ein potenzieller Nutzen für die Funktion der Bauchspeicheldrüse und der Leber. Eine frühzeitige Anwendung von HEMT bei Kleinkindern kann das Fortschreiten der Krankheit voraussichtlich weiter verzögern oder gar verhindern. Herausforderungen bestehen in der Etablierung valider Biomarker - insbesondere für jüngere Kinder, unerwünschten Arzneimittelwirkungen und der Entwicklung neuartiger Therapien für Mutationen, die auf die HEMT nicht ansprechen. Die vorliegende Übersichtsarbeit beschreibt die Effektivität und Sicherheit bei Kindern unter 12 Jahren, sowie das zukünftige therapeutische Potential der HEMT. Ein besonderes Augenmerk wird dabei auf die Notwendigkeit eines frühzeitigen Therapiebeginns zur Verbesserung des langfristigen Verlaufs gelegt.

Keywords

cystic fibrosis - cystic fibrosis transmembrane regulator - modulator therapy - highly effective CFTR modulator therapy

Schlüsselwörter

Mukoviszidose - Cystische Fibrose - Cystische Fibrose Transmembran Regulator - CFTR Modulator Therapie

Publication History

Article published online:
10 December 2024

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