Use of an ang-(1-7) receptor agonist in acute lung injury

Abstract

The present invention refers to a peptidic or non-peptidic angiotensin-(1-7) (Ang-(1-7)) receptor agonist, preferably a Mas receptor agonist, for the prevention and / or treatment of acute lung injury, preferably acute respiratory distress syndrome.

Description

[0001]The present invention refers to a peptidic or non-peptidic angiotensin-(1-7) (Ang-(1-7)) receptor agonist, preferably a Mas receptor agonist, for the prevention and / or treatment of acute lung injury, preferably acute respiratory distress syndrome.BACKGROUND OF THE INVENTION[0002]With age-adjusted incidences of 86.2 per 100,000 person-years and overall mortality rates of ˜43%, acute lung injury (ALI) and its most severe form, the acute respiratory distress syndrome (ARDS), remain a major cause of death in intensive care (1,2). The pathological hallmarks of the disease comprise diffuse alveolo-capillary injury and an increased lung permeability associated with a strong inflammatory response (3,4). These changes underlie the clinical presentation which is characterized by an acute onset, severe hypoxemia and a proteinaceous lung oedema. Despite a multitude of large multi-centric clinical trials to explore the potential of various therapeutic strategies including the use of glucoc...

AI Technical Summary

Benefits of technology

[0021]In one embodiment, the peptidic agonist is a derivative or analogue of the Ang-(1-7) peptide, the derivative or analogue comprising an amino acid exchange, deletion or insertion. Preferably, the derivative or analogue has conserved or better agonistic properties.

[0058]The term “endogenous Ang-(1-7)” means that Ang-(1-7) is endogenously produced by the subject's body to be treated. An (increased) endogenous production of Ang-(1-7) can be the result of a stimulation of its generation from Ang II, e.g. by pharmacologically activating ACE2, by blocking the AT1a receptor, or by inhibiting the degradation of Ang II to Ang III by APA. Similarly, endogenous Ang-(1-7) production can be increased by stimulation of its generation from Ang I by NEP. An (increased) endogenous production can also be the result of a gene therapeutic intervention, e.g. by overexpressing ACE2 or a construct that generates directly Ang-(1-7) or one of its precursors. An increased concentration of endogenously produced Ang-(1-7) can also result from a reduced degradation of Ang-(1-7) e.g. by pharmacological inhibition of ACE which degrades Ang-(1-7) to Ang-(1-5).

Problems solved by technology

Despite a multitude of large multi-centric clinical trials to explore the potential of various therapeutic strategies including the use of glucocorticoids, ketoconazole, lisofylline, alprostadil, inhaled NO or supplemented surfactant (5-7), no therapeutic pharmacological intervention could so far improve the clinical outcome of ALI / ARDS.

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