HL1513 (IMD) / Handok - LARVOL DELTA

Gene therapy for Friedreich ataxia cardiomyopathy: safety and preliminary assessment of efficacy (ASGCT 2026) - "Interestingly, comparison of the most recent mFARS neurologic scale to pre-therapy demonstrated improvement in 47%, stabilization in 47% and worsening in 6%. Conclusion This interim data suggests that a single intravenous administration of AAVrh.10hFXN to individuals with FA cardiomyopathy is generally safe and biologically active, increasing cardiac FXN expression, improving a key marker of cardiac structure, reducing a serum biomarker relevant to cardiomyocyte integrity and improving or stabilizing neurologic function."

Clinical • Gene therapy • Ataxia • Cardiomyopathy • Cardiovascular • Friedreich ataxia • Gene Therapies • Heart Failure • Inflammation • Movement Disorders • FXN

Barley extrudates modulate the gut microbiome-metabolome axis in vitro through β-glucan fermentation and polyphenol biotransformation. (PubMed, Food Funct) - "Compared with the control, barley extrudates induced time-dependent shifts in microbiota composition, although community profiles tended to converge at later fermentation stages. Overall, genotype- and processing-driven differences translated into distinct fermentation and phenolic biotransformation footprints, highlighting the relevance of barley matrix composition in shaping the colonic fate of cereal bioactive compounds."

Journal • Preclinical

First In Human Gene Therapy For The Cardiomyopathy Of Friedreich Ataxia (HFSA 2024) - P1, P1/2 | "Baseline characteristics of the 11 dosed participants with FA-CM included 4 males, 7 females, mean age was 27.2±5.7 years, and all had GAA repeats in the shortest allele >700. Cardiac MRI showed concentric remodeling/hypertrophy (left ventricular (LV) mass 139.2±39.2 g; LV mass index 75.0±18.7 g/m2, relative wall mass 1.24±0.30 g/ml), with preserved LV ejection fraction (66.7±4.5%) and elevated serum high sensitivity troponin I (420.7±626.1 pg/ml). There were no serious adverse events related to therapy."

Gene therapy • Late-breaking abstract • P1 data • Ataxia • Cardiomyopathy • Cardiovascular • Friedreich ataxia • Gene Therapies • Heart Failure • Hypertrophic Cardiomyopathy • Movement Disorders • FXN

Tobramycin-induced secretion of P. aeruginosa 5′ tRNA-fMet halves in outer membrane vesicles suppresses lung inflammation via AGO2-mediated gene silencing (NACFC 2023) - "Although inhaled tobramycin increases lung function in people with CF (PwCF), the density of P. aeruginosa in the lungs is only modestly reduced. Our study reveals that tobramycin increases the abundance of 5′ tRNA-fMet halves in OMVs secreted by P. aeruginosa The OMVs deliver 5′ tRNA-fMet halves to CF-hBECs, and the 5′ tRNA-fMet halves suppress IL- 8 secretion by interacting with MAPK10, IKBKG, and EP300 transcripts through an AGO2-mediated mechanism. Thus, tobramycin, in part, improves outcomes in PwCF by decreasing inflammation and neutrophils in BALF that lead to a decline in lung function. In addition, to our knowledge, this is the first report to demonstrate that prokaryotic 5′ tRNA halves regulate gene expression in a eukaryotic host by an AGO2-mediated mechanism."

Infectious Disease • Inflammation • Pneumonia • CXCL8 • EP300 • MAPK10

Host-pathogen interactions in a cystic fibrosis polymicrobial infection model (NACFC 2023) - "Primary wt, CF (Phe508del/Phe508del), and CF plus elexacaftor-tezacaftor-ivacaftor (ETI) human bronchial epithelial cells (hBECs) (n = 5/group) were treated with processed uninoculated ASM plus mucin (processed control) or poly-microbial bEVs. Polymicrobial bEVs elicit a robust inflammatory response in wt and CF hBECs and reduce CFTR Cl– secretion. Thus, polymicrobial bEVs reduce the ability of ETI to improve Phe508del CFTR Cl– secretion, an effect that is predicted to reduce the ability of ETI to clear polymicrobial infections. Studies are underway to investigate the mechanism whereby bEVs enhance inflammation in wt and CF hBECs and reduce the efficacy of ETI."

Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • CX3CL1 • CXCL3 • TNFA

Rocket-miR, a translational launchpad for miRNA-based antimicrobial drug development (NACFC 2023) - "The Rocket-miR application currently supports 24 recog-nized human pathogens that are relevant to numerous diseases, including CF, COPD, urinary tract infection, and pneumonia. The application code was designed to be easily extensible to other human pathogens that commonly colonize individuals with different diseases and lead to hospital-acquired infections. By designing Rocket-miR as an accessible, point-and-click web application, we have made miRNA target prediction accessible to a broad audience of researchers."

Chronic Obstructive Pulmonary Disease • Immunology • Infectious Disease • Nephrology • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • MIRLET7B

RESPIRE: Searchable, downloadable multi-omic data sets for lung disease research (NACFC 2023) - "This application will make multi-omic data sets related to lung disease more findable, accessible, interoperable, and reusable (FAIR) by members of the CF research community in the best traditions of the FAIR data movement [4]."

Chronic Obstructive Pulmonary Disease • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

Chemoattraction of Pseudomonas aeruginosa PAO1 to bovine bile in a novel, cystic fibrosis-derived bronchial epithelial cell model (NACFC 2022) - "Our experimental model demonstrates how P . aeruginosa colonization in the CF lung may be preceded or enhanced by chemotacticresponses to bile. These results further buttress the hypothesis that bilecontributes to colonization and pathogenesis of P. aeruginosain the lung, particularly in PwCF."

Cystic Fibrosis • Fibrosis • Gastroenterology • Gastroesophageal Reflux Disease • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases