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NeuroRestore

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 compounds 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 with 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 different preclinical 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 function in neurons, 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, is involved in cognitive impairment related to both neurodegenerative processes seen in Alzheimer’s and Parkinson’s disease, but also in other cognitive indications 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. NeuoRestore compounds have demonstrated efficacy in preclinical models for depression, which has been further supported by data in a recently published article in the highly respected publication 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. The study was completed on schedule in the second quarter of 2020, with results showing that ACD856 was well-suited for further clinical development. Continued clinical trials were initiated in late 2020, also according to plan. The results of the SAD study in August 2021 showed that the compound was well tolerated  in humans. In the third quarter of 2021 the MAD study was also initiated and both of these studies, which are part of the phase I program for the drug candidate, have the primary purpose of assessing safety and tolerability in humans. 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, validation of the target mechanism will be strengthened and the potential of licensing agreements regarding ACD856, or the entire NeuroRestore platform, will increase considerably.

For more information and material: see here 

The video below briefly shows how a compound from the NeuroRestore program acts in the brain.

AlzeCure’s primary drug candidates within NeuroRestore – ACD856 and ACD857 – act as BDNF/NGF signaling enhancers. The biological mechanism that the compounds affect enable their use in several different diseases in which the same signal pathway is disrupted.
These indications include:

Cognitive dysfunction linked to:

– Alzheimer’s disease
– Parkinson’s disease
– TBI and other head injuries
– Sleep disruptions
– Complications from major surgery

Depression

 

The figure below shows the expected growth in the number of cases of dementia between 2015 and 2050. The largest increase in number of cases of dementia and Alzheimer’s is expected to accur in low and medium income countries (LMIC), since these countries are expected to demonstrate a higher relative improvement in quality of life than high-income countries (HIC), which leads to an increased life expectancy. The need for treatment continues to be very high since there are currently no satisfactory treatment options for such patients.