A novel neuroregenerative approach using ETB receptor agonist, IRL-1620, to treat CNS disorders

Title:

A novel neuroregenerative approach using ETB receptor agonist, IRL-1620, to treat CNS disorders

Creator:

Gulati, A., Hornick, M. G., Lavhale, M. S., and Briyal, S.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:21bf878b-f3be-45e0-a8ef-f4541c822670
uuid:21bf878b-f3be-45e0-a8ef-f4541c822670
issn:0862-8408

Subject:

fyziologie člověka, human physiology, Endothelin, ETB receptors, Neuroregeneration, Alzheimer’s disease, Ischemic stroke, Amyotrophic lateral sclerosis, 14, and 612

Type:

model:article and TEXT

Format:

print, bez média, and svazek

Description:

Endothelin B (ETB) receptors present in abundance the central nervous system (CNS) have been shown to have significant implications in its development and neurogenesis. We have targeted ETB receptors stimulation using a highly specific agonist, IRL-1620, to treat CNS disorders. In a rat model of cerebral ischemia intravenous administration IRL-1620 significantly reduced infarct volume and improved neurological and motor functions compared to control. This improvement, in part, is due to an increase in neuroregeneration. We also investigated the role of IRL-1620 in animal models of Alzheimer’s disease (AD). IRL-1620 improved learning and memory, reduced oxidative stress and increased VEGF and NGF in Aβ treated rats. IRL-1620 also improved learning and memory in an aged APP/PS1 transgenic mouse model of AD. These promising findings prompted us to initiate human studies. Successful chemistry, manufacturing and control along with mice, rat and dog toxicological studies led to completion of a human Phase I study in healthy volunteers. We found that a dose of 0.6 μg/kg of IRL-1620 can be safely administered, three times every four hours, without any adverse effect. A Phase II clinical study with IRL-1620 has been initiated in patients with cerebral ischemia and mild to moderate AD., A. Gulati, M. G. Hornick, S. Briyal, M. S. Lavhale., and Seznam literatury

Language:

English

Rights:

http://creativecommons.org/publicdomain/mark/1.0/
policy:public

Source:

Physiological research | 2018 Volume:67 | Number:Suppl 1

Harvested from:

CDK

Metadata only:

false