Aperture Therapeutics announced the launch of a first-in-class matrix metalloproteinase-9 (MMP9) antisense oligonucleotide (ASO) programme, APRTX-003, targeting amyotrophic lateral sclerosis (ALS) by modulating key drivers of motor neuron degeneration. The initiative, developed by the San Carlos-based biotech, represents a novel RNA-targeting strategy designed to suppress MMP9—an extracellular protease implicated in pathogenic neuroinflammation and neurodegeneration associated with ALS—at the mRNA level, potentially overcoming limitations seen with small molecules and antibodies.
MMP9 activity has been shown to be elevated in the spinal cord, cerebrospinal fluid and serum of ALS patients and in preclinical models, where its dysregulation contributes to degradation of protective neuronal structures and amplification of inflammatory responses. Prior research indicates that reducing MMP9 activity can slow motor neuron loss, delay functional decline and extend survival in animal models.
Aperture’s APRTX-003 programme leverages its proprietary genetic and machine-learning guided ASO design platform to identify potent oligonucleotides capable of achieving robust knockdown of MMP9 mRNA and protein, while attenuating inflammatory biomarkers in human iPSC-derived microglia. The company also developed a humanised MMP9 knock-in mouse model to support translational pharmacology studies.
According to Aperture, this MMP9 ASO approach complements its broader pipeline of precision RNA medicines targeting microglial dysfunction and neuroinflammation across ALS, frontotemporal dementia, Alzheimer’s and related neurodegenerative diseases, with the goal of restoring homeostasis and slowing disease progression.
