Host: Paul Doghramji, MD Guest: Gregory S. Sawicki, MD, MPH Even though there currently isn’t a cure for cystic fibrosis, there may finally be hope on the horizon for the more than 70,000 people around the world who are living with this debilitating disease. Joining Dr. Paul Dogramji to talk about the emerging treatment options for cystic fibrosis is Dr. Gregory Sawicki, Director at the Cystic Fibrosis Center and Assistant Professor of Pediatrics at Harvard Medical School. 

Cystic Fibrosis in Focus

An In-Depth Look at the Evolution of Cystic Fibrosis Treatments

A phase 3, multi-center, multinational, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of levofloxacin inhalation solution (APT-1026) in stable cystic fibrosis patients. Flume PA, VanDevanter DR, Morgan EE, Dudley MN, Loutit JS, Bell SC, Kerem E, Fischer R, Smyth AR, Aaron SD, Conrad D, Geller DE,Elborn JS. J Cyst Fibros. 2016 Jul;15(4):495-502. doi: 10.1016/j.jcf.2015.12.004. Epub 2016 Feb 4. Abstract RATIONALE: For patients with cystic fibrosis (CF), the use of inhaled antibiotics has become standard of care to suppress chronic Pseudomonas airways infection. There are limited antibiotic options formulated and approved for inhaled use and antibiotic efficacies attenuate over time, making additional inhaled antibiotic classes desirable. APT-1026 (levofloxacin inhalation solution, LIS) is a fluoroquinolone in development for management of chronic P. aeruginosa airways infection in patients with CF. OBJECTIVES: To compare the safety and efficacy of a 28-day course of treatment with LIS 240mg or placebo BID in persons ≥12years old with CF and chronic P. aeruginosa infection. METHODS: A multinational, randomized (2:1), double-blinded study of LIS and placebo over 28days in CF patients ≥12years with chronic P. aeruginosa infection. Time to exacerbation was the primary endpoint. FEV1 (% predicted) and patient-reported ...

Journal of Cystic Fibrosis: Efficacy and Safety of Levofloxacin Inhalation Solution (APT-1026) in Stable Cystic Fibrosis Patients

A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR. Tosco A, De Gregorio F, Esposito S, De Stefano D, Sana I, Ferrari E, Sepe A, Salvadori L, Buonpensiero P, Di Pasqua A, Grassia R, Leone CA,Guido S, De Rosa G, Lusa S, Bona G, Stoll G, Maiuri MC, Mehta A, Kroemer G, Maiuri L, Raia V. Cell Death Differ. 2016 Aug;23(8):1380-93. doi: 10.1038/cdd.2016.22. Epub 2016 Apr 1. AbstractWe previously reported that the combination of two safe proteostasis regulators, cysteamine andepigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosistransmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (P<0.001) in Phe508del/Phe508del or Phe508del/null-Cftr (but not in Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal cells from patients bearing different class II CFTR mutations, either in homozygous or compound heterozygous form, responded to the treatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both ...

A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR. Tosco A, De Gregorio F, Esposito S, De Stefano D, Sana I, Ferrari E, Sepe A, Salvadori L, Buonpensiero P, Di Pasqua A, Grassia R, Leone CA,Guido S, De Rosa G, Lusa S, Bona G, Stoll G, Maiuri MC, Mehta A, Kroemer G, Maiuri L, Raia V. Cell Death Differ. 2016 Aug;23(8):1380-93. doi: 10.1038/cdd.2016.22. Epub 2016 Apr 1. AbstractWe previously reported that the combination of two safe proteostasis regulators, cysteamine andepigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosistransmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (P

Cell Death and Differentiation: A Novel Treatment of Cystic Fibrosis Acting On-Target

Microbial colonization and lung function in adolescents with cystic fibrosis. Hector A, Kirn T, Ralhan A, Graepler-Mainka U, Berenbrinker S, Riethmueller J, Hogardt M, Wagner M, Pfleger A, Autenrieth I, Kappler M, Griese M, Eber E, Martus P, Hartl D. J Cyst Fibros. 2016 May;15(3):340-9. doi: 10.1016/j.jcf.2016.01.004. Epub 2016 Feb 5. Abstract With intensified antibiotic therapy and longer survival, patients with cystic fibrosis (CF) are colonized with a more complex pattern ofbacteria and fungi. However, the clinical relevance of these emerging pathogens for lung function remains poorly defined. The aim ofthis study was to assess the association of bacterial and fungal colonization patterns with lung function in adolescent patients with CF. Microbial colonization patterns and lung function parameters were assessed in 770 adolescent European (German/Austrian) CF patients in a retrospective study (median follow-up time: 10years). Colonization with Pseudomonas aeruginosa and MRSA were most strongly associated with loss of lung function, while mainly colonization with Haemophilus influenzae was associated with preservedlung function. Aspergillus fumigatus was the only species that was associated with an increased risk for infection with P. aeruginosa.Microbial interaction analysis revealed three distinct microbial clusters within the longitudinal course of CF lung disease. ...

Journal of Cystic Fibrosis: Microbial Colonization and Lung Function in Adolescents With Cystic Fibrosis

Cystic fibrosis (CF) is one of the most prevalent global congenital disorders, affecting some 70,000 individuals worldwide and 30,000 children and adults in the United States. While clinical efforts are expanding worldwide to improve diagnostic testing and treatment approaches for this progressive lung disease, targeted therapies for CF against any specific mutation remain elusive. The Cystic Fibrosis in Focus series gathers the latest information from leading medical experts devoted to advancing knowledge in pursuit of treating patients with CF. With education spanning topics such as pinpointing CF's underlying genetic basis, identifying specific mutations, improving clinical detection methods, and providing more targeted therapies, The Cystic Fibrosis in Focus series delivers the critical tools needed to improve care for CF patients.​ In Partnership with

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Cystic Fibrosis in Focus

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