Cystic Fibrosis: Novel Strategies of Diagnosis and Treatments

Dear Colleagues,

Cystic fibrosis (CF) is the most common fatal genetic disease in Caucasians, with over 2000 known mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR).

The introduction of CFTR modulators (CFTRm), approved by the FDA in 2019, has revolutionized the lives of CF patients, with improved pulmonary functions, nutritional status, and quality of life. However, a challenging group of patients remains those who are not eligible for CFTRm (especially patients with severe stop mutations, which are more prevalent in certain populations).

We are launching a Special Issue entitled “Cystic Fibrosis: Novel Strategies of Diagnosis and Treatments”. The aim of this subject is to highlight the diagnosis and treatment of CF in the era of CFTRm—methods to obtain sputum cultures in patients who do not expectorate sputum after the initiation of CFTRm; effects of CFTRm that have not been studied so far; novel therapies for those ineligible to CFTRm—gene therapy, mRNA therapy; and the diagnosis and treatment of challenging bacteria (such as non-tuberculous mycobacteria—NTM) in patients with and without CFTRm.

These topics will help more deeply understand the new face of CF diagnosis and treatments—major advances in the field versus the challenges that remain.

Dr. Michal Gur
Prof. Dr. Lea Bentur
Guest Editors

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• cystic fibrosis
• CFTR modulators
• stop mutations
• gene therapy
• mRNA therapy
• novel therapies
• rare pathogens

Title: Feasibility and safety evaluation of a novel airway clearance system in patients with CF and bronchiectasis
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Abstract: Airway mucus obstruction is a key characteristic of chronic obstructive lung diseases. Airway clearance techniques (ACTs) are an essential component of the daily therapy, with the goal of removing thick mucus from the airways, breaking the vicious cycle of infection-loss of function, preventing lung function deterioration and delaying disease progression.. AD had shown positive outcomes but is challenging for patients to learn and perform independently. Synchrony medical developed LibAirtyTM, a novel airway clearance system adaptive to patients’ breathing cycle, designed based on the physiological principles of Autogenic Drainage (AD). The system promotes breathing at different lung volumes by synchronizing sequential chest compressions delivered via an inflatable vest with controlled breathing, using its internal sensors and a guidance app.

Title: New insights on the pathogenesis of Mycobacterium Abscessus infection in CF patients
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Title: In Vitro Antimicrobial Activity of Novel Antimicrobial Peptide OMN51 Against Multi-drug Resistant Pseudomonas
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Abstract: BACKGROUND There has been a rising incidence of multi-drug resistance (MDR) Pseudomonas aeruginosa (PSA), the most common and virulent of microbial infections among people with cystic fibrosis (pwCF). OMN51 is a novel bioengineered bactericidal antimicrobial peptide developed by Omnix Medical Ltd. It is a beta-hairpin antimicrobial peptide derived from the innate immune system of Capitella teleta, which selectively disrupts the bacterial membrane, exerting a bactericidal effect on target bacteria. OMN51 distinguishes between host cells and bacteria based on membrane lipid composition and net electric charge of bacterial membrane, and therefore is inert against host cells. It compromises the integrity of bacterial outer membranes, leading to proton gradient depletion and bacterial cell lysis, irrespective of bacterial antibiotic resistance profile. We aimed to explore the effectiveness of OMN51 in MDR PSA in sputum derived from pwCF. METHODS Sputum cultures were collected from pwCF and PSA strains were isolated, cultured and incubated. The bacterial inoculum was treated with OMN51 in culture wells and MIC values were measured. MIC results were compared to antimicrobial activity of other antibiotics on the PSA bacterial strains. RESULTS OMN51 was active against all 35 clinical isolates, irrespective of resistance profile. The MIC range was narrower (4–16 µg/mL) compared to the other antimicrobial agent. Potent inhibitory effect on PSA bacteria was found, with MIC of ≤ 16 µg/mL, between the different tested bacterial strains. The lowest MIC observed was 4 µg/mL, both in sensitive and resistant/MDR strains. OMN51 was not susceptible to the antimicrobial resistance mechanisms that affected other antimicrobial agents tested. CONCLUSIONS This study shows in vitro PoC of OMN51 antimicrobial activity against MDR PSA in clinical isolates from sputum of pwCF. OMN51 mechanism is believed to have a lower propensity to develop antimicrobial resistance. Currently, OMN51 is being developed as an inhaled therapy for pwCF. Further clinical trials are planned to corroborate the initial in vitro findings.

Title: Survey on adverse events associated with elexacaftor/tezacaftor/ivacaftor therapy in a large cohort of patients with CF
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