Aperture Therapeutics Announces First-In-Class MMP9 Antisense Oligonucleotide Program for ALS

SAN CARLOS, Calif., Jan. 6, 2026 /PRNewswire/ -- Aperture Therapeutics, a biotechnology company pioneering next-generation precision medicines for neurodegenerative diseases, today announced the advancement of its matrix metalloproteinase-9 (MMP9) antisense oligonucleotide (ASO) program, APRTX-003, for the treatment of Amyotrophic Lateral Sclerosis (ALS). The program targets chronic neuroinflammation and neurodegeneration, two core pathological drivers of motor neuron degeneration in ALS and represents a first-in-class RNA-targeting approach to modulate this genetically and mechanistically validated pathway.

MMP9 is a secreted extracellular protease that plays a dual role in the central nervous system, contributing to normal synaptic remodeling under physiological conditions while driving pathological neuroinflammation and neurodegeneration when aberrantly activated. Recent studies demonstrate that microglia-derived MMP9 promotes neurodegeneration by digesting the neuroprotective extracellular nets that shield motor neurons from stress as well as amplifying pathogenic neuroinflammation. Evidence from human patient samples and multiple preclinical models demonstrates that MMP9 expression and activity is greatly elevated in the spinal cord, cerebrospinal fluid, and serum of ALS patients and in other age-related neurodegenerative diseases. Conversely, both genetic depletion and pharmacological inhibition of MMP9 slow motor neuron degeneration, delay motor function decline, and extend survival in preclinical models.

"Despite longstanding and compelling biological evidence implicating MMP9 in ALS, prior efforts to drug this target have failed due to fundamental limitations of small molecules and antibodies, including poor selectivity and off-target toxicity." said Martin Jacko, PhD, Founder and CEO of Aperture Therapeutics. "By directly suppressing MMP9 at the RNA level, our antisense approach is designed to overcome these historical barriers and precisely modulate a pathway that has long been recognized as central to ALS pathogenesis."

Aperture's MMP9 program leverages the company's proprietary platform integrating human genetic evidence and machine-learning-guided oligonucleotide design. Using high-throughput screening and chemical optimization, Aperture has identified multiple potent MMP9-targeting ASOs capable of achieving robust knockdown of MMP9 mRNA and protein while attenuating inflammatory biomarkers implicated in ALS pathology in human iPSC-derived microglia. To enable translational pharmacology studies, the company developed a proprietary humanized MMP9 knock-in mouse model expressing the human transcript.

The MMP9 program complements Aperture's broader pipeline of genetics-based oligonucleotide therapeutics targeting microglial dysfunction and neuroinflammation across ALS, FTD, AD and related neurodegenerative diseases. Together with its CD33 program, the company is building a portfolio of precision RNA medicines designed to restore microglial homeostasis and slow neurodegeneration by modulating pathways supported by strong human genetic and translational evidence.

About Aperture Therapeutics

Aperture Therapeutics is a preclinical biotechnology company founded in 2022 dedicated to developing novel oligonucleotide therapies inspired by human genetic resilience. The Company leverages a proprietary platform integrating multi-omics analyses, machine-learning-guided ASO/siRNA design, and humanized in vivo models to generate genetically validated, clinically relevant targets. Aperture has received funding from the National Institute of Neurological Disorders and Stroke (NINDS/NIH), Mission BioCapital, Age1, Ferocity Capital, XEIA Venture Partners, Conscience VC, LongGame, and Tensor Ventures.

For more information, please visit www.aperturetx.com or follow the company on LinkedIn at @Aperture Therapeutics.

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SOURCE Aperture Therapeutics