NRG Therapeutics Scores $18M to Target Mitochondrial Dysfunction in Parkinson's, ALS
Prof. Seth Masters, VP Discovery Biology at NRG Therapeutics/Company Courtesy
With a fresh $18 million in the bank, NRG Therapeutics is ready to put its novel mitochondrial approach to the test for two devastating neurodegenerative disorders—Parkinson’s and ALS.
The British company has a new approach to targeting mitochondrial dysfunction to slow or halt the progression of these diseases, which have no cure.
Inhibiting the mitochondrial permeability transition pore (mPTP) has been proven to prevent cell death. mPTP is a key driver of disease pathology in Parkinson’s and ALS. To this point, there is nothing on the market to inhibit the mechanism.
“The molecular composition of the permeability transition pore has not really been defined,” Dr. Neal Miller, NRG CEO, told BioSpace.
One protein modulated the pore, but targeting in a drug sense proved impossible to get through the blood barrier, a common problem in the neuroscience field.
Enter what Miller calls a “breakthrough for mitochondrial biology.”
NRG has identified a new protein that either modulates or is part of the pore. The discovery opens the door to understanding how the protein regulates the pore, its role in diseases and will facilitate drug discovery.
Miller said NRG has identified what they believe is the "first orally bioavailable and CNS penetrant, small molecule inhibitors of the pore.”
These unique aspects were leveraged for the company’s Series A, announced Wednesday. Led by Omega Funds, the round included founding investor Parkinson’s Virtual Biotech and new Australia-based investor Brandon Capital. NRG has also received funding from the Michael J. Fox Foundation, a grant Miller called “validating” of the company’s science.
Miller and CSO Richard Rutter worked at GSK together for nearly a decade before moving on to Auspherix, an early-stage anti-infectives company, where they met NRG's now COO.
Although mitochondrial dysfunction has been recognized as a hallmark of Parkinson’s for several decades, its exact role has historically been undetermined.
Recent research, out of UCL Queen Square Institute of Neurology, has new evidence that mitochondrial dysfunction is propagating the disease phenotype for Parkinson’s and ALS, Miller said.
“If you inhibit the mPTP, you prevent that new inflammation and you rescue neurons and you rescue mice in ALS model,” he said.
The team is targeting a novel pathway for ALS – a neuroinflammatory-triggering protein that activates an innate immune sensor, STING. STING was identified by Seth Masters at Australia’s Walter and Eliza Hall Institute of Medical Research, who is joining the NRG team as vice president of Discovery Biology.
His WEHI lab will include scientists from NRG for a research collaboration running over the next two years.
“I can envisage both scenarios in which we may move ahead with a single molecule that would have utility in both diseases ... Ideally, we would deliver a normal medicine that can be dosed once or twice daily, for ALS or Parkinson's.”
Miller said the diseases are not the same and believes the acute need in ALS is stronger. While Parkinson’s affects a much larger population, ALS is a much faster-progressing disease. Life expectancy is two to four years; current treatments add an additional three to six months to patients’ lives. Results in the clinic will determine the path forward for both diseases.
The company is expecting an IND submission in late 2024 or early 2025.