NRG Therapeutics Ltd., a clinical-stage neuroscience company, has announced that the first participants have been dosed in its first-in-human Phase 1 clinical trial of NRG5051, a potential disease-modifying therapy for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) and Parkinson’s.
NRG5051 is an orally bioavailable, CNS-penetrant inhibitor of the mitochondrial permeability transition pore (mPTP), acting via a novel mitochondrially localized protein regulator. The Phase 1 randomized, double-blind trial, conducted at the Centre for Human Drug Research (CHDR) in Leiden, The Netherlands, combines single and multiple ascending doses to evaluate safety, tolerability, and pharmacokinetics in healthy volunteers. Trial results are expected by the end of 2026 and will guide dose selection for future patient studies.
Mitochondrial dysfunction is a key contributor to neuronal death in ALS/MND and Parkinson’s. Motor neurons and substantia nigra neurons have high energy demands and are particularly sensitive to mitochondrial health. Pathological proteins such as TDP-43 in ALS/MND and alpha-synuclein in Parkinson’s drive mitochondrial toxicity, inflammation, and neurodegeneration. Preclinical studies have shown that NRG5051 is both neuroprotective and anti-inflammatory, supporting its potential as a disease-modifying therapy.
ALS/MND remains a rapidly progressing neurodegenerative disease with limited treatment options, particularly for sporadic cases. Parkinson’s disease, one of the fastest-growing neurodegenerative disorders worldwide, currently has no therapies that slow disease progression, with existing treatments providing only temporary symptom relief. NRG5051 represents a first-in-class approach targeting the underlying mitochondrial pathology common to these conditions.
