Aperture Therapeutics Advances CD33-Targeting Antisense Oligonucleotide APRTX-001 for Neurodegenerative Diseases
核心洞察
Aperture Therapeutics (搜索) has nominated APRTX-001 (搜索), a first-in-class CD33 (搜索)-targeting antisense oligonucleotide, as its development candidate for treating frontotemporal dementia (搜索) and amyotrophic lateral sclerosis (搜索).
The therapy replicates protective effects of naturally occurring CD33 (搜索) loss-of-function variants that are associated with increased resilience to neurodegenerative disease and reduced neuroinflammation.
APRTX-001 (搜索) is advancing through IND-enabling studies and represents a precision RNA-targeting approach to overcome historical failures of small molecules and antibodies targeting this pathway.
Aperture Therapeutics (搜索) announced the nomination of APRTX-001 (搜索) as its development candidate, marking a significant advancement in precision medicine for neurodegenerative diseases. The first-in-class CD33 (搜索)-targeting antisense oligonucleotide (ASO) is designed for the treatment of Frontotemporal Dementia (搜索) (FTD) and Amyotrophic Lateral Sclerosis (搜索) (ALS), with strong potential for indication expansion into Alzheimer's disease (搜索) (AD). The program is now advancing through investigational new drug (IND)-enabling studies.
Novel Mechanism Targets Microglial Dysfunction
APRTX-001 (搜索) replicates the protective effects of naturally occurring CD33 (搜索) loss-of-function variants, which are associated with increased resilience to neurodegenerative disease, reduced neuroinflammation, and lower levels of pathological biomarkers linked to neural aging and degeneration. CD33 serves as a critical regulator of neuroinflammatory signaling, suppressing microglial phagocytosis and promoting a pro-inflammatory glial phenotype. The therapy's inhibition of CD33 restores microglial homeostasis and reduces chronic neuroinflammation.
Elevated CD33 (搜索) expression is consistently observed in patient tissues across ALS, FTD, AD, and Parkinson's disease (搜索) (PD), underscoring the central role of microglial dysregulation in disease pathogenesis. This broad expression pattern suggests the potential for APRTX-001 (搜索) to address multiple neurodegenerative conditions through a common mechanism.
Overcoming Historical Development Challenges
"Although CD33 (搜索) has long been recognized as an important regulator of neuroinflammation in neurodegenerative disease, prior attempts to drug this pathway with small molecules or antibodies have failed due to modality-associated challenges and poor translation in preclinical models, underscoring the need for a more precise RNA-targeting approach," said Martin Jacko, PhD, Founder and CEO of Aperture Therapeutics (搜索). "By directly modulating CD33 at the RNA level, APRTX-001 (搜索) overcomes these historical barriers with a precision approach grounded in human genetics."
Proprietary Platform and Translational Models
The discovery and optimization of potent CD33 (搜索) modulators was supported by funding from the National Institute of Neurological Disorders and Stroke (NINDS/NIH). Because CD33's structure and function are not fully conserved in rodent models, Aperture developed a proprietary humanized CD33 knock-in mouse model to enable translationally relevant target validation and therapeutic testing.
In parallel, the company is advancing additional programs across key neuroinflammatory and neurodegenerative mechanisms and developing a microglia-specific drug delivery technology to further enhance the precision of therapeutics targeting neuroinflammation.
Company Background and Funding
Aperture Therapeutics (搜索) 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.