A stroke that causes severe paralysis that requires months of rehabilitation, and then still leaves the patient with a permanent disability …. repeat concussion in the boxing ring or on the football field that leaves the athlete with early-onset dementia …. repeated exposure to loud noise that leaves soldiers and musicians with permanently hearing loss …. a severe epileptic seizure that leaves the sufferer with permanent impairment. What these people all have in common is that they have experienced neural damage from excitotoxicity.
The human brain has about 100 billion interconnected neurons (cells that carry electrical signals). By some estimates, our brain has as many as 1000 trillion connections. So, death of just a few neurons can have significant knock-on effects, which is what is behind excitotoxicity. And when a neuron dies its contribution to the brain network is lost forever.
Electrical signals are passed across those connections by chemicals known as neurotransmitters. It only requires a tiny amount of neurotransmitter to stimulate the receiving neuron to trigger an electrical signal. The normal response of a neuron to injury, however, is to dump its stores of neurotransmitters, the result being that those other dozens or hundreds of neurons connected to that damaged neuron receive an overload of neurotransmitters, causing them to over-respond to the point where they become stressed and die. With stoke, this cascade of cell death radiates out from the original injury over days and weeks, and by the time it stops, the final area of brain death can be up to 10-times larger than the original injury.
There is no current treatment that can block excitotoxicity. Nyrada believes that it is on track to deliver an effective treatment based on the ability to block the excitotoxicity process before it can take hold. This belief is based on two breakthroughs.
The first breakthrough was pioneering research conducted by neuroscientists at the University of New South Wales (UNSW Sydney) led by Professor Gary Housley who identified a protein called TRPC3 that has having a central role in the excitotoxicity process. Noxopharm partnered with the university to identify a family of compounds capable of inhibiting the injury signalling in neurons linked to this protein. Drug candidate NYX-104 emerged as the most promising, based on laboratory studies.
The second breakthrough was a drug delivery technology known as LIPROSE which enabled those compounds to cross the blood-brain barrier. Using this technology, the university team has shown that NYX-104 strikingly decreases damage to the brain of mice following the induction of a stroke, providing the company with in vivo proof-of-concept.
The goal is to bring NYX-104 into the clinic as a first-in-class drug to reduce the degree of paralysis following stroke and concussion and other excitotoxicity-associated disorders.