Hendrik Fischer's research while affiliated with APEPTICO Forschung und Entwicklung GmbH and other places

Publications (14)

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
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
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...

Citations

... In our study, a combination of three immunosuppressants with variable target-specific action exhibited superior clinical outcome, less re-hospitalisation with reduced mortality than the combination of two immunosuppressants. COVID-19 infection at severe stage causes lethal lung injury mostly by triggering cytokine storm leading to ARDS, and about one-third of hospitalised patients with COVID-19 symptoms develop ARDS [21]. Several studies found that the extrapulmonary systemic hyperinflammatory syndrome (ESHS), also known as cytokine storm, in COVID-19 which is developed due to over expression of pro-inflammatory cytokines and other mediators in the host body, known as the third-phase of COVID-19 infection, has Table 2. Clinical outcomes in patients with severe COVID-19 pneumonia treated with baricitinib plus secukinumab (Group A) or baricitinib plus secukinumab plus tocilizumab (Group B). ...
... Experiments were done as previously described. [43][44][45][46] Briefly, cells were grown in 100 µL cell culture dishes in 5% CO 2 incubator in DMEM medium supplemented with 5% fetal bovine serum. Medium was then aspirated, cells washed twice with PBS. ...
... Experiments were done as previously described. [43][44][45][46] Briefly, cells were grown in 100 µL cell culture dishes in 5% CO 2 incubator in DMEM medium supplemented with 5% fetal bovine serum. Medium was then aspirated, cells washed twice with PBS. ...
... It has been approved by the Austrian Federal Office for Safety in HealthCare to treat COVID-19 patients. Solnatide is a small synthetic peptide (fewer than 20 amino acids) applied as an aerosol directly in the lower airways [109]. ...
... Solnatide, AP301) organized by APEPTICO, Vienna, Austria have been conducted at the Hospital of the Medical University Vienna, Austria. A double-blind placebo-controlled phase I study evaluating spirometry, exhaled NO, vital signs, ECG, safety laboratory and quantification of peptide in plasma, associated with six ascending inhaled doses of the TIP peptide in 48 healthy male subjects (Schwameis et al., 2014) demonstrates no serious, local, or dose-limiting adverse events with very ...
... TNF -through its LLD-and solnatide -a LLD mimic-activate ENaC, which is expressed at the apical plasma membrane of epithelial and endothelial cells in various tissues and organs, including lungs, colon, kidneys [17,18]. This activity has been measured electrophysiologically as an increase in amiloride-sensitive sodium current in cells expressing ENaC [11,12,19,20]. ENaC is the rate-limiting step for Na + uptake and it plays a critical role in lung fluid clearance in physiological and disease conditions [17,21]. ...
... TNF -through its LLD-and solnatide -a LLD mimic-activate ENaC, which is expressed at the apical plasma membrane of epithelial and endothelial cells in various tissues and organs, including lungs, colon, kidneys [17,18]. This activity has been measured electrophysiologically as an increase in amiloride-sensitive sodium current in cells expressing ENaC [11,12,19,20]. ENaC is the rate-limiting step for Na + uptake and it plays a critical role in lung fluid clearance in physiological and disease conditions [17,21]. ...
... Spatial separation of the functions of TNF into distinct regions in the molecule might explain the apparent contradictory roles of this cytokine, which, on the one hand, exacerbates inflammation and edema formation through its receptor-binding domains and, on the other hand, activates edema reabsorption through its lectinlike domain [1,5]. Residues Cys101-Glu116 of wild-type human TNF (hTIP) participate in the activation of ENaC [3,12]. The lectin-like activity of TNF (TIP) domain of TNF was mapped 28 years ago in view of its trypanolytic effect on purified bloodstream forms of Trypanosoma brucei brucei [3]. ...