£2.68M Award to NRG Therapeutics Supports Work Into Potential DMT

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by Steve Bryson, PhD |

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NRG Therapeutics has received a £2.68M (about $3.4 million) award to support preclinical work into small molecule disease-modifying therapies for neurodegenerative conditions such as Parkinson’s disease.

The two-year Biomedical Catalyst award given the company is for early stage research in treatments to protect mitochondria in the brain, and is partly funded by the government-backed agency Innovate UK.

“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,” Arthur Roach, PhD, director of research at Parkinson’s UK and a board member of NRG, said in a press release.

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NRG has a pipeline of orally available small molecules designed to reach cells of the brain and spinal cord, referred to as the central nervous system, and block the mitochondrial permeability transition pore (mPTP). This protein forms on the inner membrane of energy-producing mitochondria and, when open due to an accumulation of calcium or other stimuli, can lead to cell death.

“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,” Roach said. “NRG’s small molecules are the first orally bioavailable and CNS-penetrant inhibitors of the mPTP.”

mPTP has been implicated in Parkinson’s, caused by the death of brain cells that produce dopamine, a neurotransmitter produced by the body to send messages between nerve cells to control movement, learning and memory, sleep, and mood.

The potential therapies may also help with the neurodegenerative disorder amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, caused by the death of nerve cells that control voluntary movements.

In vitro (test-tube) experiments have shown that NRG’s investigational small molecules protected mitochondria and prevented the death of brain cells. In animal models, blocking mPTP in the brain limited nerve cell death, lowered inflammation, and extended survival. If successful, the project may lead to the first disease-modifying therapy to slow or halt Parkinson’s disease progression.

“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,” said Neil Miller, PhD, NRG’s co-founder and CEO.

Over two years, the funding — with NRG contributing 30% — will help to advance the mPTP blockers from optimizing lead candidates to the regulatory-based toxicology studies needed to support clinical trials.

The project aims to generate a package of preclinical data based on a safe and well-tolerated therapy candidate that can penetrate the brain, protect mitochondria, and prevent brain cell death.

NRG has previously received funding from the Parkinson’s Virtual Biotech, the medicinal development arm of Parkinson’s UK, The Michael J. Fox Foundation, and an Innovate UK EDGE grant, which provided scientific and commercial support for the company’s research program.