Aperture Therapeutics Unveils Groundbreaking ALS Treatment with MMP9 Antisense Oligonucleotide

Aperture Therapeutics, a pioneering biotechnology firm focused on developing precision medicines for neurodegenerative diseases, has made a significant advancement in the battle against Amyotrophic Lateral Sclerosis (ALS). On January 6, 2026, the company introduced its first-class matrix metalloproteinase-9 (MMP9) antisense oligonucleotide program, known as APRTX-003. This promising initiative seeks to combat two critical pathological aspects of ALS: chronic neuroinflammation and neurodegeneration.

What is MMP9?

MMP9, an extracellular protease, plays a dual role in the central nervous system. Under normal physiological conditions, it aids in synaptic remodeling, ensuring healthy neural function. However, when activated inappropriately, MMP9 contributes to pathological neuroinflammation and degeneration, which are key factors in the progression of ALS. Recent research highlights that MMP9, when derived from microglia, exacerbates neurodegeneration by disrupting neuroprotective extracellular nets and intensifying harmful neuroinflammatory responses.

Evidence from ALS patients and preclinical studies indicate that MMP9 levels are markedly elevated in their spinal cords, cerebrospinal fluid, and serum. Notably, inhibiting or depleting MMP9 genetically or pharmacologically has been shown to slow motor neuron degeneration, delay declines in motor function, and prolong survival in experimental models.

Challenges in Drug Development

According to Martin Jacko, PhD, the Founder and CEO of Aperture Therapeutics, previous attempts to target MMP9 with small molecules and antibodies have faced significant obstacles, such as poor selectivity and the risk of off-target toxicity. Jacko emphasized that the innovative antisense approach undertaken by Aperture aims to directly suppress MMP9 at the RNA level, thereby providing a precise solution to modulate this crucial pathway linked to ALS.

Leveraging Advanced Technologies

Aperture’s MMP9 program takes advantage of the company’s proprietary platform, which combines human genetic evidence with machine-learning algorithms to design oligonucleotides. The firm was able to identify several potent MMP9-targeting antisense oligonucleotides that effectively reduce MMP9 mRNA and protein levels, as well as lower inflammatory biomarkers relevant to ALS pathology, utilizing human-derived induced pluripotent stem cells (iPSCs).

To facilitate translational studies, the company also developed a unique humanized MMP9 knock-in mouse model, which expresses the human variant of the gene. This model is pivotal for advancing pharmacological studies that will further elucidate the therapeutic potential of the MMP9 program.

A Broader Perspective

The MMP9 project fits into a wider pipeline at Aperture Therapeutics, consisting of genetic-based oligonucleotide therapies that target neuroinflammation and microglial dysfunction in ALS, Frontotemporal Dementia (FTD), Alzheimer’s Disease (AD), and other similar neurodegenerative conditions. Alongside its CD33 program, Aperture is working towards creating a comprehensive portfolio of precision RNA medicines designed to restore microglial balance and mitigate neurodegeneration, reinforced by solid human genetic evidence.

About Aperture Therapeutics

Founded in 2022, Aperture Therapeutics is a preclinical biotechnology company dedicated to pioneering oligonucleotide therapies inspired by human genetic resilience. Their proprietary platform integrates multi-omics analyses, advanced ASO/siRNA design facilitated by machine-learning, and humanized in vivo models aimed at generating clinically relevant, genetically validated targets. The firm has garnered support from esteemed organizations including the National Institute of Neurological Disorders and Stroke (NINDS/NIH), Mission BioCapital, and several venture partners.

For more insights on Aperture Therapeutics and their endeavors, visit www.aperturetx.com or follow the company on LinkedIn at @Aperture Therapeutics.