Cannabinoid development company Incannex Healthcare (ASX: IHL) has commenced a pre-clinical animal trial investigating the neuroprotective capabilities of its lead candidate IHL-216A.
The trial will introduce rodents to head trauma, implemented consistently in a highly-controlled environment to inflict a reproducible injury.
Eight separate rodent cohorts will be administered components or combinations of IHL-216A at varying doses soon after the trauma has been inflicted.
The rodents will then undertake behavioural tests at various intervals to assess their neurocognitive and motor function.
Incannex will also monitor secondary injury cascades, assess structural damage to the brain using magnetic resonance imaging, and perform micro-scale cellular analysis post-mortem to discern and compare neuronal damage across the cohorts.
Incannex said the animal study would establish optimal combination dosages for an upcoming in-human clinical trial.
The company believes there is an optimal fixed dose of active pharmaceutical ingredients (APIs) within IHL-216A which, if administered soon after head trauma is first incurred, will reduce neuro-excitation, neuro-inflammation, cerebral blood flow and cerebral oxygen consumption (CMRO2).
The result could potentially provide overall neuroprotection – defined as reduced neuronal cell death or disruption – and improved recovery from the neurocognitive and motor deficits that result from traumatic brain injury.
Incannex’s animal trial follows the filing of a provisional patent in October covering IHL-216A to be used in combination with a halogenated volatile anaesthetic agent in the treatment of traumatic brain injury and concussion.
Cannabidiol and halogenated volatile anaesthetic agents are known to cause a reduction in neuro-excitation, which is thought to be a key step in the pathway resulting in the reduction of neuro-cellular damage and traumatic brain injury.
The idea of the resulting product is that similar to the Penthrox methoxyflurane pen, otherwise known as the “green whistle” that has seen that company achieve sales and a market capitalisation of $400 million plus.
Managing director Joel Latham said that early intervention would be key.
“It is the belief of [our] drug discovery team that treatment of moderate head injuries with a hyperacute bolus of cannabidiol plus volatile anaesthetic agent is neuroprotective,” he said.
“The combination drug must be administered in a format allowing rapid crossing of the blood brain barrier to allow it to prophylactically reduce activation of neuro-inflammation and neuro-excitability.
“By preventing the chemotaxis and build-up of the inflammatory mediators, the cascade of secondary cerebral damage is ablated.”
Traumatic brain injury accounts for approximately 10 million deaths and hospitalisations across the world on an annual basis and there is currently no approved pharmaceutical agent to treat patients.
Major cases of traumatic brain injury are most commonly managed through surgical intervention by decompressive craniotomy which involves the removal of skull segments to reduce intracranial pressure.
IHL-216A is being assessed on its ability to protect the brain against the main injury mechanisms that cause cell death and other negative consequences in the days and weeks following head trauma in sports, and all other applicable scenarios resulting in head trauma.
The drug has been designed to satisfy World Antidoping Authority and Australian Anti-Doping Authority specifications for use by athletes at risk of brain injury and chronic traumatic encephalopathy, which is a brain condition associated with repeated blows to the head.