Novel disease-modifying medicines are being developed to combat debilitating chronic neuro-degenerative disorders.

Neuroscience company NRG Therapeutics Ltd is applying pioneering work in the field of mitochondrial biology to develop first-in-class treatments for Parkinson’s, MND (also known as ALS) and, potentially, other neurodegenerative disorders.

Its approach is based on inhibiting the mitochondrial permeability transition pore (mPTP) in brain cells which has been shown to be neuroprotective in several preclinical models of Parkinson’s and MND.

NRG has received a Biomedical Catalyst (BMC) award to fund pre-clinical development of its novel small molecule disease-modifying medicines.

The £2.68 million early-stage BMC award part-funded by the government-backed agency Innovate UK is supporting a 24-month project.

Mitochondria are the powerhouses or batteries of cells and therefore essential for maintaining cell health but there is now a substantial body of evidence showing that mitochondrial failure or dysfunction is common across many degenerative diseases.

NRG’s investigational new drugs have been shown in vitro to protect mitochondria and prevent the death of brain cells and therefore have the potential to halt or significantly slow the progression of disease in individuals with Parkinson’s or MND.

Dr Arthur Roach, Director of Research at Parkinson’s UK and a Board member of NRG Therapeutics, explained: “What has limited the pharmaceutical industry to date from exploring mPTP inhibitors as novel therapeutic treatments, has been the poor central nervous system (CNS) penetration of known mPTP inhibitors.

“NRG’s small molecules are the first orally bioavailable and CNS-penetrant inhibitors of the mPTP. We are pleased to support NRG in developing its promising discoveries into new drug treatments that could transform the lives of people with Parkinson’s.”

If successful, the project would deliver the first disease-modifying medicine to halt or slow disease progression for people with Parkinson’s who are currently treated through management of disease symptoms only. PD affects over six million individuals and is the fastest-growing neurological disorder in the world, thus presenting a major healthcare challenge for society.

In addition, NRG is targeting a novel pathological mechanism in MND that was identified in 2020 by its collaborators in Australia. MND is a devastating neurodegenerative disease that typically leads to death within 3-5 years of diagnosis and for which the current gold-standard treatment extends life by ~3 months only.

NRG Therapeutics’ co-founder and CEO Dr Neil Miller, added: “Mitochondrial dysfunction is a common underlying pathology in many degenerative diseases and there is a substantial body of preclinical data available which demonstrates that inhibition of the mPTP in the brain prevents neuronal cell death, reduces neuroinflammation and extends survival in animals. With our unique discoveries, NRG is in a leadership position in this field to develop first-in-class CNS-penetrant mPTP inhibitors”.

The BMC award (of which NRG contributes 30% of the funding) will, over 24 months, advance NRG’s proprietary mPTP inhibitors from lead optimisation through to completion of IND-enabling GLP-toxicology studies with its lead asset.

Specifically, it will generate a preclinical data package that demonstrates NRG’s drug candidates penetrate into the brain, protect mitochondria, prevent brain cell death in animal models and are safe & well tolerated following chronic dosing.

It follows an earlier award to NRG of an Innovate UK EDGE grant which provided invaluable scientific and commercial insights for NRG’s MND programme.