In Alzheimer’s disease, the nerve cells cease functioning as they should, which leads to a deterioration of memory and learning. AlzeCure has identified drug-like compounds that stimulate neurotrophic signaling pathways, thereby strengthening nerve cell function and improving memory.
NeuroRestore is a platform of symptomatic drug candidates for diseases where cognitive ability is impaired, such as Alzheimer’s. NeuroRestore stimulates several important signal pathways in
the brain, which among other things leads to improved cognition. In preclinical studies with NeuroRestore, we have been able to demonstrate that our drug candidates not only boost communication between nerve cells but also improve cognitive ability. The drug candidates in NeuroRestore stimulate signaling of neurotrophins, the most well-known of which is Nerve Growth
Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF). These neurotrophins are important for maintaining nerve cell function and communication, which are impaired in cognitive disorders.BDNF plays an important role for nerve cell function and communication in the areas of the brain that are essential for our cognitive ability, such as the hippocampus, located in the temporal lobe. In addition, special “cholinergic neurons” in the basal forebrain depend on NGF to maintain their biological function, but also to survive. Loss of cholinergic neurons in the basal forebrain, as well as dysfunction of normal neuron function and communication in the hippocampus are early signs of Alzheimer’s and correlate with cognitive impairment. The drug candidates in the NeuroRestore platform strengthen the signaling of these two important neurotrophins, which results in improved memory and learning – something that AlzeCure has been able to demonstrate in several differentpreclinical models. The levels of NGF and BDNF are disrupted in many diseases and signaling is reduced. This reduced function impairs both communication
between the contact surfaces at nerve ends and the neuronal function, which gives rise to cognitive impairment. There is also genetic support for this target mechanism – a genetic variation of BDNF in humans, leading to a reduction in BDNF secretion, has been linked to cognitive impairment related to neurodegenerative processes seen in Alzheimer’s and Parkinson’s disease, but also in other cognitive disorders such as traumatic brain injury and sleep disorders. AlzeCure also considers there to be a potential for adding further indications based on the specific target mechanism. There is also strong scientific support for this target mechanism in depression. NeuroRestore compounds have had significant effects in preclinical models of depression, which are
further strengthened by data in a recently published article in the renowned journal Cell1. In the preclinical trials, ACD856, the leading drug candidate in the NeuroRestore platform, has been able to demonstrate that it can strengthen signaling in the intended pathway and improve cognitive ability. Among other things, the compound has been able to show that it can reverse age-induced memory impairment and strengthen the effect of existing drugs (acetylcholinesterase inhibitors), which AlzeCure views as a competitive advantage. AlzeCure started the first clinical trial with ACD856 in December 2019 and after favorable results, the phase Ia clinical trial was initiated in December 2020. The study start is on schedule and the results of this study are expected to be ready during the summer of 2021. After completed phase I studies, the company plans to carry out a signal detection study for ACD856 in order to be able to evaluate signals of efficacy for the drug candidate at an early stage of the development process. If an early effect is found the validation of the target mechanism will be strengthened and the potential for licensing agreements regarding ACD856, or the entire NeuroRestore platform, will increase considerably.
1) Casarotto et al., Antidepressant drugs act by directly
binding to TRKB neurotrophin receptors, Cell (2021)
The video below briefly shows how a compound from the NeuroRestore program acts in the brain.