A receptor tyrosine kinase-based target for ischemic stroke and other CNS injuries. Target modulation reduces reactive astrocyte activity and glial scarring to promote functional recovery. Validated in a non-human primate (NHP) model of CNS injuries, that is more predictive of disease progression in humans than current models.
New, clinically relevant NHP model for testing drugs for CNS disorders.
- Novel target for attenuating astrocyte activity in adult brain to prevent glial cell scar formation in the days and weeks post ischemic event
- Potential for ‘First in Class’ drugs for ischemic stroke and other brain disorders
The major factor limiting functional recovery in adult stroke patients is formation of scar tissue in the brain during the sub-acute period. This glial scarring (refractory to regeneration) is formed by reactive astrocytes and is exaggerated 2-4 weeks post injury.
Using a proprietary NHP model with excellent translatability to humans, researchers from Monash University’s Australian Regenerative Medicine Institute have shown that the infant brain undergoes less astrocyte activity after stroke, correlating to smaller glial scarring that is more permissible to functional recovery (Fig.1).
The team identified pathways and targets that regulate astrocyte activity after injury in the infant. Using compositions that stimulate the ‘infant pathway’, strong inhibition of astrocyte preactivity was shown in primate cell models in vitro. This could minimize glial scar formation in the adult brain (especially during the sub-acute period) which, in turn, could drive functional recovery.
Proof-of-mechanism has been shown using the NHP model where target modulation suppressed the reactive astrocyte response after brain injury, resulting in a reduction of the glial scar (Fig. 2), as well as suppressing secondary recruitment and reduction in apoptotic cells at the ischemic core. Primate studies using a selective target ligand indicate significant neuron sparing.
Attenuating astrocyte reactivity can also be applied to improve outcomes after other brain and spinal cord injuries, to suppress the severity and invasiveness of glioblastomas. This strategy can be integrated onto brain-stimulating electrodes to minimise scar formation, increasing the longevity of existing treatments.
Researcher and technical details
Contact for this technology
Dr Kathy Nielsen
Senior Commercialisation Manager Monash Innovation
+61 3 9905 5918
US provisional 62/250380 and Australian application 2015252036 filed on methods to reduce glial scarring and treat CNS damage.
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