danegaptide (ZP1609) / Zealand Pharma - LARVOL DELTA

Effect of Danegaptide on Gap Junction Preservation at the Blood-Brain Barrier after Sudden Cardiac Arrest (ACEP 2023) - No abstract available

Cardiovascular

Scar border zone mass and presence of border zone channels assessed with cardiac magnetic resonance imaging are associated with ventricular arrhythmia in patients with ST-segment elevation myocardial infarction. (PubMed, Europace) - P=N/A, P2 | "Scar characterization with CMR indicates that a combination of ≥17.2 g BZ mass and the presence of BZ channels had the strongest association with subsequent VA in STEMI patients."

Journal • MRI • Atrial Fibrillation • Cardiovascular • Myocardial Infarction • Ventricular Tachycardia

Activating Connexin43 gap junctions primes adipose tissue for therapeutic intervention. (PubMed, Acta Pharm Sin B) - "Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of the β -adrenergic receptor agonist Mirabegron and FGF21. Additionally, combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced efficacy. In light of these findings, we propose a model in which connecting adipocytes via Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage it. Thus, Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue."

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • FGF21

Connexin 43 gap junction-mediated astrocytic network reconstruction attenuates isoflurane-induced cognitive dysfunction in mice. (PubMed, J Neuroinflammation) - "Our results reveal a novel mechanism of the GJ-Cx43-mediated astrocytic network involved in isoflurane-induced neuroinflammation and cognitive impairments, which provides new mechanistic insight into the pathogenesis of POCD and identifies potential targets for its treatment."

Journal • Preclinical • Alzheimer's Disease • Anesthesia • Cognitive Disorders • Immunology • Inflammation • IL1B • IL6

Danegaptide Prevents TGFβ1-Induced Damage in Human Proximal Tubule Epithelial Cells of the Kidney. (PubMed, Int J Mol Sci) - "Furthermore, danegaptide inhibited TGFβ1-induced changes in the expression and secretion of key adipokines, cytokines, chemokines, growth factors and interleukins. The data suggest that as a gap junction modulator and hemichannel blocker, danegaptide has potential in the future treatment of CKD."

Journal • Chronic Kidney Disease • Fibrosis • Immunology • Inflammation • Nephrology • Renal Disease • TGFB1

Gap-134, a Connexin43 activator, prevents age-related development of ventricular fibrosis in Scn5a mice. (PubMed, Pharmacol Res) - "Chronic administration of a potent and selective gap junction modifier, Gap-134 (danegaptide), between 45 and 60 weeks, increased Cx43 expression and phosphorylation on serine 368 and prevented Cx43 delocalization...In conclusion, the present study demonstrates that the age-dependent decrease of Cx43 expression is involved in the ventricular fibrotic process occurring in Scn5a mice. Finally, our study suggests that gap junction modifier, such as Gap-134, could be an effective anti-fibrotic agent in the context of age-dependent fibrosis in progressive cardiac conduction disease."

Journal • Preclinical • Fibrosis • Immunology • GJA1

Danegaptide Enhances Astrocyte Gap Junctional Coupling and Reduces Ischemic Reperfusion Brain Injury in Mice. (PubMed, Biomolecules) - "Furthermore, administration of danegaptide in a novel mouse brain ischemia/reperfusion model showed significant decrease in infarct volume. Taken together, this study provides evidence for the therapeutic potential of danegaptide in ischemia/reperfusion stroke."

Journal • Preclinical

A human in vitro platform for the evaluation of pharmacology strategies in cardiac ischemia. (PubMed, APL Bioeng) - "ZP1609 significantly improved the drastic drop in conduction velocity and enabled a greater recovery. This model represents a new preclinical platform for studying cardiac ischemia with human cells, which does not rely on biomarker analysis and has the potential for screening novel cardioprotective drugs with readouts that are closer to the measured clinical parameters."

Biomarker • Journal • Preclinical