Aperture Therapeutics has announced the nomination of APRTX-001, a development candidate designed to target CD33 via antisense oligonucleotide (ASO) technology, for the treatment of Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS). The company said it is advancing the program through IND-enabling studies, marking a major step toward clinical development.
The therapy draws on human genetic data: certain loss-of-function variants in CD33 are linked to greater resilience against neurodegeneration, reduced neuroinflammation and lower levels of pathological biomarkers, according to Aperture. CD33 is known to suppress microglial phagocytosis and promote a pro-inflammatory glial state, and its overexpression has been observed in patient tissues across ALS, FTD, Alzheimer’s disease and Parkinson’s disease. By suppressing CD33 at the RNA level, APRTX-001 is designed to restore microglial homeostasis and dampen chronic inflammatory signaling.
Aperture noted that previous efforts to target CD33 with small molecules or antibodies have faced translational challenges, largely due to modality limitations and poor performance in traditional animal models. To overcome this, the company developed a humanized CD33 knock-in mouse model to validate its ASO in a more clinically relevant system.
The discovery and optimization of the ASO were supported by funding from the National Institute of Neurological Disorders and Stroke (NINDS). In parallel, Aperture is also working on a microglia-specific delivery technology to improve precision of its neuroinflammation-targeted therapies.
