Aperture advances RNA-targeting treatment for ALS
APRTX-003 targets inflammation, neurodegeneration
- Aperture is developing APRTX-003, an RNA-targeting therapy for ALS.
- APRTX-003 targets an enzyme linked to neuroinflammation and nerve cell damage.
- The therapy is in preclinical development, with IND-enabling studies underway.
Aperture Therapeutics said it is advancing its RNA-targeting therapy APRTX-003 as a potential treatment for amyotrophic lateral sclerosis (ALS).
The therapy, currently in preclinical development, is designed to reduce the production of matrix metalloproteinase-9 (MMP-9) by targeting its template RNA molecule. When overactive, this enzyme may lead to neuroinflammation and nerve cell damage in ALS. These processes contribute to the loss of motor neurons, the nerve cells that control voluntary movement, driving ALS symptoms.
APRTX-003 is in investigational new drug (IND)-enabling studies, according to Aperture’s website. These studies typically evaluate a therapy’s safety and pharmacological properties in preclinical models and are required before clinical testing in people can begin.
“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,” Martin Jacko, PhD, Aperture’s founder and CEO, said in a company press release. “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.”
People with ALS and other age-related diseases that cause progressive nerve cell damage have elevated MMP-9 levels and greater enzyme activity. Lowering MMP9 levels, either through genetic approaches or drug treatment, has been shown to slow motor neuron degeneration, delay loss of motor function, and extend survival in preclinical models.
Targeting messenger RNA
APRTX-003 belongs to a class of therapies called antisense oligonucleotides (ASOs), short strands of genetic material that bind to a gene’s messenger RNA — the template used to make a protein — and target it for destruction. The treatment is designed to target MMP9’s messenger RNA and suppress its production.
Aperture’s development approach begins with human genetic data that helps identify biological pathways or therapeutic targets that may protect nerve cells from damage. Artificial intelligence is then used to design drug candidates that target the specific molecules.
The company has developed a mouse model that produces the human form of MMP9, allowing researchers to evaluate APRTX-003 in a disease-relevant system.
Aperture is also advancing other antisense therapies to treat ALS, frontotemporal dementia, Alzheimer’s disease, and related neurodegenerative conditions.
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