Argenica Therapeutics (ASX:AGN) xaranetide shows significant neuroprotection in preclinical concussion study
Argenica Therapeutics has reported positive preclinical efficacy data for its lead drug candidate, ARG 007 (xaranetide), in a rodent repeated mild traumatic brain injury (mTBI), or concussion, model.
The study, undertaken in collaboration with researchers from Curtin University and the Perron Institute for Neurological and Translational Science, reported that xaranetide reduced multiple key drivers of secondary brain injury following repeated mTBI, including neuroinflammation, oxidative stress and axonal damage.
Highlights
ARG 007 (xaranetide) demonstrated significant efficacy in reducing the secondary injury effects in a repeated mTBI preclinical animal model, with activity across neuroinflammation, oxidative stress and axonal injury.
A single intravenous dose of 1 mg/kg administered 30 minutes after repeated mTBI significantly reduced neuroinflammation, oxidative stress and axonal damage, with the effect lasting up to 11 days post injury.
Xaranetide significantly reduced astrocyte and microglial activation across multiple brain regions, lowered markers of oxidative stress and reduced neurofilament light, a marker of neuroaxonal injury, in the ventral tegmental area.
According to the company, the findings are consistent with previously reported efficacy in multiple moderate and severe traumatic brain injury models and demonstrate biological activity across the spectrum of traumatic brain injury severity.
The study evaluated biomarkers associated with secondary brain injury following repeated mTBI.
According to the announcement, a single intravenous dose of xaranetide administered following 2 mild traumatic brain injuries given 24 hours apart reduced GFAP positive astrocyte reactivity in the dentate gyrus of the hippocampus to levels comparable with sham animals.
The study also found significant reductions in Iba1 positive microglial reactivity across the cortex, corpus callosum and dentate gyrus, with all 3 brain regions returning to sham levels by Day 11 following injury.
The announcement states that these anti neuroinflammatory effects were sustained for at least 11 days following injury.
The announcement also reported reductions in MnSOD immunoreactivity, a marker of oxidative stress, in both the cortex and ventral tegmental area, together with a significant reduction in neurofilament light, a marker of neuroaxonal injury, in the ventral tegmental area.
The figures included in the announcement show these biomarkers were reduced to non injury (sham) control levels when analysed at Day 11 following injury.
Argenica Managing Director Dr Liz Dallimore commented,
"This is another independent demonstration of xaranetide's efficacy in TBI, adding to a growing body of evidence across mild, moderate, and severe injury models, and reinforcing its potential as a disease modifying therapy for repeated concussion. Based on these results, Argenica is now considering next steps to advance xaranetide's development in this indication."
The company states that these results extend the evidence base for xaranetide beyond its lead acute ischaemic stroke program by demonstrating a consistent, mechanistically aligned protective effect across 3 distinct preclinical injury models, namely single moderate to severe traumatic brain injury, ischaemic stroke and repeated mild traumatic brain injury.
The announcement also states that repeated mild traumatic brain injury and concussion represent a large, currently underserved population, including contact sport athletes, military personnel and survivors of domestic violence, for which no approved pharmacological neuroprotective therapy exists.
According to the company, these data provide a scientific basis to explore repeated mild traumatic brain injury and concussion as a complementary indication alongside its core stroke program.
The company says it is considering the next steps to advance xaranetide's development in the repeated mild traumatic brain injury indication.