Bernhard Fischer

Bernhard Fischer
APEPTICO Forschung und Entwicklung GmbH | APEPTICO · R&D

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21
Publications
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Publications

Publications (21)
Article
Full-text available
Tumor necrosis factor (TNF) is a homotrimer that has two spatially distinct binding regions, three lectin-like domains (LLD) at the TIP of the protein and three basolaterally located receptor-binding sites, the latter of which are responsible for the inflammatory and cell death-inducing properties of the cytokine. Solnatide (a.k.a. TIP peptide, AP3...
Article
Full-text available
Previous in vitro studies have indicated that tumor necrosis factor (TNF) activates amiloride-sensitive epithelial sodium channel (ENaC) current through its lectin-like (TIP) domain, since cyclic peptides mimicking the TIP domain (e.g., solnatide), showed ENaC-activating properties. In the current study, the effects of TNF and solnatide on individu...
Article
Full-text available
The synthetically produced cyclic peptides solnatide (a.k.a. TIP or AP301) and its congener AP318, whose molecular structures mimic the lectin-like domain of human tumor necrosis factor (TNF), have been shown to activate the epithelial sodium channel (ENaC) in various cell- and animal-based studies. Loss-of-ENaC-function leads to a rare, life-threa...
Article
Full-text available
Regulation of the epithelial sodium channel (ENaC), which regulates fluid homeostasis and blood pressure, is complex and remains incompletely understood. The TIP peptide, a mimic of the lectin-like domain of TNF, activates ENaC by binding to glycosylated residues in the extracellular loop of ENaC-α as well as to a hitherto uncharacterized internal...
Article
Full-text available
Rationale: Alveolar liquid clearance is regulated by Na 1 uptake through the apically expressed epithelial sodium channel (ENaC) and basolaterally localized Na 1-K 1-ATPase in type II alveolar epithelial cells. Dysfunction of these Na 1 transporters during pulmonary inflammation can contribute to pulmonary edema. Objectives: In this study, we sough...
Article
Full-text available
Rationale: Alveolar liquid clearance is regulated by Na(+) uptake through the apically expressed epithelial sodium channel (ENaC) and basolaterally localized Na(+)-K(+)-ATPase in type II alveolar epithelial cells. Dysfunction of these Na(+) transporters during pulmonary inflammation can contribute to pulmonary edema. Objectives: In this study, w...
Article
AP301 is an activator of ENaC-mediated Na(+) uptake for the treatment of pulmonary permeability edema in acute respiratory distress syndrome (ARDS). The purpose of this "first-in-man" study was to examine local and systemic safety and systemic exposure of ascending single doses of AP301, when inhaled by healthy male subjects. In a double-blind, pla...
Article
Full-text available
AP301, a cyclic peptide, comprising the human tumour necrosis factor lectin like domain (TIP domain) sequence, is currently being developed as a therapy for lung oedema and has been shown to reduce extravascular lung water and improve lung function in a mouse, rat and pig model. The current paradigm for liquid homeostasis in the adult mammalian lun...
Article
Rationale: Aims of this study were to investigate whether the TIP peptide, mimicking the alveolar liquid clearance (ALC)-promoting lectin-like domain of TNF, is able to activate amiloride-sensitive Na+ transport in H441 cells and to directly interact with specific ENaC domains. Methods: Peptide effects on Na+-uptake in cells pretreated or not with...
Conference Paper
Full-text available
Pulmonary edema is a major complication of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) which is associated with higher mortality. AP301 is a synthetic peptide whose structure is based on the lectin-like domain of human Tumour Necrosis Factor alpha. The water soluble peptide can be administered into the lung by oral inhala...
Article
The amiloride-sensitive epithelial sodium channel (ENaC) plays a prominent role in sodium uptake from alveolar fluid and is the major component in alveolar fluid clearance in normal and diseased lungs. The lectin-like domain of TNF-α has been shown to activate amiloride-sensitive sodium uptake in type II alveolar epithelial cells. Therefore, severa...

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Project (1)
Project
Exploration of safety, tolerability and clinical efficacy of solnatide investigative medicinal product (solnatide IMP) in patients infected with the 2019 new Cornoavirus. SOLNATIDE will clinically test peptide-based products targeting life-threatening pulmonary diseases (such as oedematous respiratory failure, acute lung injury). APEPTICO’s lead-compound solnatide IMP has been designed for the therapeutic treatment of patients with Acute Respiratory Distress Syndrome (ARDS) and various forms of PPO.