Algorae Pharmaceuticals reports positive pre-clinical neuronal cell viability results

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Algorae Pharmaceuticals (ASX:1AI) has announced positive results from in vitro pre-clinical studies assessing its AI-116 for treating neurodegenerative disorders, including those characterised by dementia.

AI-116 is Algorae’s combination drug candidate comprising donepezil hydrochloride (Donepezil), an acetylcholinesterase inhibitor (AChE inhibitor), and cannabidiol (CBD).

AChE inhibitors are FDA registered first-line treatments for Alzheimer’s Disease, which are also prescribed off-label for other neurodegenerative disorders, including Parkinson’s Disease and vascular dementia.

The company said in-vitro assays were conducted to further assess the therapeutic potential of AI-116 by comparing the viability of neuronal cells in the presence of Amyloid with varying exploratory doses of AI-116 against the two drugs alone.

The in vitro assays measured cell viability and drug synergy, which occurs when the combined effect of two drugs is superior to the sum of their individual effects.

In these assays, neuroblastoma cells were concurrently treated with varying doses of CBD and donepezil in the presence of Amyloid β. Cell viability was measured using the MTT assay. Improvement in cell viability was determined as a percentage increase in cell survival over cells treated with Amyloid alone.

The company said the control arm of the in vitro study demonstrated high levels of toxicity when neuronal cells were exposed to Amyloid. It said the improvements in cell viability observed with the AChE inhibitor and CBD alone were substantially improved with the optimal fixed dose combination of AI-116.

These results demonstrate that the combination of CBD and Donepezil synergise to increase the neuroprotective effect in neuronal cells that are exposed to toxic Amyloid β, with the observed combined effect of the two drugs on cell viability is 33% greater than what would be expected if we added together the effects of each drug used alone," said the company.

Principal Investigator Professor Garrie Arumugam said, “These preliminary in vitro results are very promising, showing a clear pattern of neuronal cell protection and synergistic method of action. I am eager to further investigate the implications of these findings and how they could pave the way for new insights and potentially advancements in drug development.”

The company said additional analyses, including RNA sequencing analysis, will now commence to assess the therapeutic mechanism associated with the use of AI-116, including assessments for neuroinflammation, which plays a multifaceted role in the pathogenesis of neurodegenerative disorders and dementia.