Algorae Pharmaceuticals’ AI-116 dementia treatment shows promising pre-clinical results

Algorae Pharmaceuticals (ASX: 1AI) has released positive results from in vitro pre-clinical studies to assess AI-116 for the treatment of neurodegenerative disorders, including those characterised by dementia.

AI-116 is a fixed-dose combination drug candidate comprising donepezil (often marketed as ‘Aricept’) and cannabidiol (CBD).

Donepezil is already a first-line treatment for Alzheimer’s disease in a class of drugs called AChE inhibitors and is also prescribed off-label for other neurodegenerative disorders including Parkinson’s disease.

Algorae’s pre-clinical data showed that the neuroprotective effect of AI-116 exceeded that offered by donepezil alone in a model of neuronal cells exposed to amyloid β, a toxic compound associated with Alzheimer’s disease.

Therapeutic viability

In the company’s experiments, neuronal cell viability in the presence of amyloid β improved from 65.5% to 85.6% at the optimal dose of AI-116, whilst donepezil at the corresponding dose only achieved an improvement from 65.5% to 67.6%.

The assays also measured drug synergy, which is observed when the impact of two drugs in combination is superior to the sum of their individual effects.

The results demonstrated that CBD and donepezil synergise to increase the neuroprotective effect in neuronal cells exposed to amyloid β.

The observed combined effect of the two drugs on cell viability was 33% greater than what would have been expected from the effects of each drug used alone.

Accordingly, the pre-clinical data have been incorporated into provisional patent applications that pursue aspects of AI-116 and its associated therapeutic uses.

Promising results

Principal investigator Professor Garrie Arumugam said the results were promising for dementia patients.

“These preliminary in vitro results show a clear pattern of neuronal cell protection and synergistic method of action,” he said.

“I am eager to further investigate the implications of these findings and how they could pave the way for new insights and potential advancements in drug development.”

He said additional analyses including ribonucleic acid sequencing will be carried out to determine the mechanism of action associated with AI-116.

The work will include assessments for neuroinflammation, which plays a multifaceted role in the pathogenesis of neurodegenerative disorders and dementia.

Economic potential

Donepezil was first registered by the US Food and Drug Administration in 1996 for the symptomatic treatment of Alzheimer’s disease to improve cognitive function and quality of life.

The class of drugs known as AChE inhibitors to which it belongs works by increasing the levels in the brain of acetylcholine, a neurotransmitter involved in memory and learning.

AI-116 is aimed at competing with AChE inhibitors within a market size estimated to be US$21b in 2024, driven by the rising prevalence of Alzheimer’s disease and other types of dementia.