NRG Therapeutics, a clinical-stage neuroscience company, has announced that it has dosed the first participants in its first-in-human Phase 1 trial of investigational therapy for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) and Parkinson’s.

 

NRG5051 is a first-in-class, orally bioavailable, CNS-penetrant inhibitor of the mitochondrial permeability transition pore (mPTP), acting through a novel, undisclosed mitochondrially-localized protein regulator.

 

The Phase 1 study, conducted at the Centre for Human Drug Research (CHDR) in Leiden, is a randomized, double-blind, single and multiple ascending dose trial designed to evaluate safety, tolerability, and pharmacokinetics in healthy volunteers. Results are expected by the end of 2026 and will guide dosing in future patient studies.

 

The mPTP plays a key role in mitochondrial dysfunction, inflammation, and neuronal death in neurodegenerative diseases. Mitochondria are critical for energy production, especially in substantia nigra neurons (Parkinson’s) and motor neurons (ALS/MND), which are highly energy-dependent and vulnerable to damage. 

 

Pathological proteins such as TDP-43 in ALS/MND and α-synuclein in Parkinson’s are toxic to mitochondria, driving dysfunction—a common thread in both diseases. Preclinical studies show NRG5051 to be neuroprotective and anti-inflammatory.

 

NRG co-founder and CEO Neil Miller said: "The start of our first clinical trial marks a proud moment for NRG as we transition into a clinical stage company. Our ultimate objective is to establish the therapeutic efficacy of our novel mPTP inhibitors as disease-modifying medicines that are designed to slow or prevent the progression of neurodegenerative diseases, and this first-in-human trial is a significant step toward that goal.”