NRG Therapeutics is leveraging breakthrough science in the field of mitochondrial biology to identify new therapeutic targets to treat neurodegenerative disorders.
We are developing novel ‘next generation’ mitochondrial permeability transition pore (mPTP) inhibitors that are orally bioavailable and brain-penetrant. These inhibitors prevent the mitochondrial gain-of-function toxicity of misfolded TDP-43 and α-synuclein, the pathological proteins that cause the degeneration of motor neurones and dopaminergic neurones in ALS and Parkinson’s respectively. The company benefits from the drug discovery and neuroscience expertise and insights, and biotech experience of its founders, its management team and expert advisors, and world-leading scientific and drug development collaborators.
Inhibition of the mPTP prevents the aberrant release of mitochondrial DNA, a novel pathogenic pathway recently discovered to activate the innate immune system in ALS1.
Inhibition of the mPTP prevents the activation of mitochondrial mediated cell death by toxic forms of α-synuclein2.
1. TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS: Yu et al, 2020, Cell 183, 636–649
2. α-synuclein oligomers interact with ATP synthase and open the permeability transition pore in Parkinson’s disease: Ludtmann et al, 2018, Nature Communications, 9, 1-16
The mPTP has been shown to play a key pathological role in the neurodegeneration associated with Parkinson’s and ALS.
The company’s pre-clinical pipeline includes structurally-differentiated chemical series of small molecule inhibitors, with first-in-class potential, which inhibit the mPTP through a novel mechanism of action.
We aim to progress our small molecule assets with best-in-class potential into the clinic and through completion of Proof-of-Mechanism/Concept studies in patients. Our ultimate goal is to partner with leading global pharma companies to complete clinical development and commercialization.
