eluforsen (QR-010) / ProQR - LARVOL DELTA

Dose-response effects of acute exercise intensity on state anxiety among women with depression. (PubMed, Front Psychiatry) - "Moderate exercise resulted in a moderate state anxiety reduction compared to QR 10 min (STAI-Y1: g = 0.59, p = 0.040) and 30 min post-exercise (STAI-Y1: g = 0.61, p = 0.032)...Prescribed moderate intensity exercise led to greater reductions in state anxiety compared to preferred at 30 m (STAI-Y1: g = 0.43, p = 0.04). These findings suggest steady-state prescribed moderate exercise reduces state anxiety in women with MDD for at least 30 min following exercise regardless of their depression severity."

Journal • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Identification of Candidate Genes for Salinity and Anaerobic Tolerance at the Germination Stage in Rice by Genome-Wide Association Analyses. (PubMed, Front Genet) - "Nineteen QTLs were close to the reported loci for abiotic stress tolerance, whereas two regions on chromosome 4 (qSGr4a/qCL4c/qRI4d and qAGr4/qSGr4b) and one region on chromosome 10 (qRI10/qCL10/ qSGr10b/qBM10) were associated with anaerobic and salinity related traits...In this study, we identified the genes involved in auxin efflux (Os09g0491740) and transportation (Os01g0976100), whereas we identified multistress responses gene OsMT2B (Os01g0974200) and a major gene OsTPP7 (Os09g0369400) involved in anaerobic germination and coleoptile elongation on chromosome 9. These promising candidates provide valuable resources for validating potential salt and anaerobic tolerance genes and will facilitate direct-seeded rice breeding for salt and anaerobic tolerance through marker-assisted selection or gene editing."

Journal

Antisense oligonucleotide eluforsen improves CFTR function in F508del cystic fibrosis. (PubMed, J Cyst Fibros) - "In F508del-CFTR homozygous subjects, repeated intranasal administration of eluforsen improved CFTR activity as measured by NPD, an encouraging indicator of biological activity."

Journal • Cystic Fibrosis • Fibrosis • Immunology • Respiratory Diseases

The Cystic Fibrosis-Like Airway Surface Layer Is not a Significant Barrier for Delivery of Eluforsen to Airway Epithelial Cells. (PubMed, J Aerosol Med Pulm Drug Deliv) - "The thickened and concentrated CF ASL does not constitute a significant barrier for delivery of eluforsen, and feasibility of oral inhalation of eluforsen is supported by these data."

Journal • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

Exploratory Study to Evaluate QR-010 in Subjects With Cystic Fibrosis ΔF508 CFTR Mutation (clinicaltrials.gov) - P1; N=18; Completed; Sponsor: ProQR Therapeutics; Recruiting ➔ Completed; N=32 ➔ 18; Trial primary completion date: Dec 2016 ➔ Sep 2016

Enrollment change • Trial completion • Trial primary completion date • Biosimilar • Fibrosis • Immunology

Evaluation of eluforsen, a novel RNA oligonucleotide for restoration of CFTR function in in vitro and murine models of p.Phe508del cystic fibrosis. (PubMed, PLoS One) - "Similarly, intranasal administration of eluforsen significantly improved nasal potential difference (NPD), and therefore CFTR conductance, in two CF mouse models. These findings indicate that eluforsen improved CFTR function in cell and animal models of p.Phe508del-CFTR-mediated CF and supported further development of eluforsen in human clinical trials, where eluforsen has also been shown to improve CFTR activity as measured by NPD."

Journal • Preclinical

Genetic dissection of yield-related traits and mid-parent heterosis for those traits in maize (Zea mays L.). (PubMed, BMC Plant Biol) - "The results revealed that (1) the inheritance of yield-related traits and MPH in the heterotic pattern improved Reid (PA) × Tem-tropic I (PB) is trait-dependent; (2) a large proportion of loci showed dominance effects, whereas overdominance also contributed to MPH for KNPR, EWPE, and KWPE; (3) marker-assisted selection for markers at genomic regions 1.09-1.11, 2.04, 3.08-3.09, and 10.04-10.05 contributed to hybrid performance per se and heterosis and were repeatedly reported in previous studies using different heterotic patterns is recommended."

Journal

Metabolite Profiling of the Antisense Oligonucleotide Eluforsen Using Liquid Chromatography-Mass Spectrometry. (PubMed, Mol Ther Nucleic Acids) - "Chain-shortened metabolites of eluforsen by 3' exonuclease were observed in mouse liver in an in vitro incubation system and by either 3' exonuclease or 5' exonuclease in liver and lung samples from an in vivo mouse and monkey study. This study provides approaches for further metabolite characterization of 2'-ribose-modified phosphorothioate oligonucleotides in in vitro and in vivo studies to support the development of oligonucleotide therapeutics."

Journal

Antisense oligonucleotide eluforsen is safe and improves respiratory symptoms in F508DEL cystic fibrosis. (PubMed, J Cyst Fibros) - "Inhaled eluforsen up to 50 mg dosed 3 times per week for 4 weeks was safe and well tolerated, showed low systemic exposure, and demonstrated improvement in CFQ-R RSS, a relevant measure of clinical benefit in CF patients."

Journal

Dose Escalation Study of QR-010 in Homozygous ΔF508 Cystic Fibrosis Patients (clinicaltrials.gov) - P1b; N=70; Completed; Sponsor: ProQR Therapeutics; Active, not recruiting ➔ Completed

Clinical • Trial completion