Amlogenyx presents preclinical data for AM805 gene therapy targeting amyloid in Alzheimer's disease

Amlogenyx Reports Preclinical Data for AM805, an AAV9 Gene Therapy Designed to Degrade Amyloid in Alzheimer's Disease Amlogenyx Inc., a Novato, California-based biotechnology subsidiary of Ultragenyx, disclosed preclinical results for [AM805](https://www.globenewswire.com/news-release/2026/03/16/3256272/0/en/Amlogenyx-Announces-Positive-Preclinical-Data-on-AM805-a-Potent-Amyloid-Degrading-Protease-for-the-Treatment-of-Alzheimer-s-Disease.html), an investigational AAV9 gene therapy encoding protective protein cathepsin A (PPCA), a lysosomal carboxypeptidase, for the treatment of Alzheimer's disease. The data, presented at the AD/PD 2026 International Conference on Alzheimer's and Parkinson's Diseases in Copenhagen, showed dose-dependent amyloid reduction in mouse models of the disease, with the company stating that the magnitude of reduction was comparable to, and in some cases exceeded, that reported for approved anti-amyloid monoclonal antibodies. AM805 represents a mechanistically distinct approach to amyloid plaque clearance. Rather than deploying antibodies to tag amyloid for immune-mediated removal, the therapy delivers a gene encoding PPCA via an AAV9 vector directly to the central nervous system. Once expressed, PPCA functions as an amyloid-degrading protease, catalytically breaking down amyloid-beta peptides within the lysosomal compartment of neurons. The company describes this as catalytic amyloid degradation, a process intended to clear both intracellular amyloid accumulations and extracellular plaques. The work was conducted in collaboration with researchers at St. Jude Children's Research Hospital, who identified PPCA as an enzyme capable of degrading amyloid with high efficiency. According to the data disclosed by Amlogenyx, studies were conducted in mouse models representing both severe and moderate Alzheimer's disease pathology, in young and aged animals. All routes of administration tested resulted in increased PPCA enzymatic activity in the brain and reduced amyloid-positive brain area in a dose-dependent manner. Aβ peptide levels, measured by 4G8-positive signal, were lowered in both intracellular and extracellular compartments. The company also reported that PPCA was delivered safely to the brains of non-human primates and achieved enzyme expression levels consistent with the therapeutic effect observed in the mouse models. The company did not disclose specific quantitative endpoints, statistical analyses, or detailed safety data from these studies. No clinical trial for AM805 has been registered on [ClinicalTrials.gov](https://clinicaltrials.gov/), and the program remains in the preclinical stage. Amlogenyx stated that AM805 is currently in IND-enabling studies and that the company plans to submit an Investigational New Drug application to the US FDA in 2027. The company did not disclose the intended route of administration for human dosing, the target patient population for first-in-human studies, or the anticipated clinical trial design. The Alzheimer's disease treatment landscape has shifted considerably in recent years with the approval of two anti-amyloid monoclonal antibodies. Lecanemab (Leqembi), developed by Eisai and Biogen, received traditional US FDA approval in [July 2023](https://www.fda.gov/news-events/press-announcements/fda-converts-novel-alzheimers-disease-treatment-traditional-approval) for early Alzheimer's disease, based on the CLARITY AD trial showing a 27% slowing of cognitive decline over 18 months compared with placebo. Donanemab (Kisunla), developed by Eli Lilly, was approved in [July 2024](https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-adults-alzheimers-disease) based on the TRAILBLAZER-ALZ 2 trial, which demonstrated a 35% slowing of decline in a combined tau and clinical endpoint population. Both therapies require chronic intravenous infusions and carry the risk of amyloid-related imaging abnormalities (ARIA), including brain edema and microhemorrhages, necessitating regular MRI monitoring. Older symptomatic therapies, including donepezil and memantine, remain in widespread use but do not modify disease progression. Aducanumab (Aduhelm), which received accelerated approval in 2021, was withdrawn from the market in January 2024. The AM805 preclinical data position the program within a small but growing cohort of gene therapy approaches to neurodegenerative disease. The theoretical appeal of a one-time gene therapy that provides sustained enzymatic degradation of amyloid is clear: it could eliminate the need for repeated infusions, potentially reduce ARIA risk by avoiding antibody-mediated immune activation, and address amyloid accumulation inside neurons, a compartment that antibody therapies do not directly access. However, these remain preclinical observations in animal models. Cross-trial comparisons between preclinical mouse data and clinical outcomes from antibody trials in humans are not methodologically valid, and the company's claims that AM805 reductions were comparable to or exceeded those of approved antibodies should be interpreted with that caveat. Gene therapy delivery to the CNS carries its own set of challenges, including vector immunogenicity, durability of transgene expression, the risk of off-target effects, and the difficulty of redosing AAV-based therapies. The non-human primate safety data referenced by Amlogenyx have not been published in peer-reviewed form, and the company did not disclose whether any adverse findings were observed in those studies. No other gene therapies targeting PPCA or cathepsin A are currently in clinical development for Alzheimer's disease, according to available registry data. The competitive set for AM805, should it advance to clinical testing, would include lecanemab and donanemab as well as several other anti-amyloid and non-amyloid programs in late-stage development. Amlogenyx is a subsidiary of [Ultragenyx](https://www.amlogenyx.com/), a company with established capabilities in AAV gene therapy manufacturing and rare disease development. Whether those capabilities translate to the scale and complexity required for an Alzheimer's disease program, which would need to reach a far larger patient population, remains to be seen. The planned 2027 IND submission, if achieved, would place AM805 among the first gene therapies to enter human testing for Alzheimer's disease, a milestone that would itself generate considerable scrutiny of both the science and the delivery platform. --- Spot something wrong? [Report an issue with this article](https://newsgen-prod.reframedata.com/feedback/am805-gene-therapy-amlogenyx-presents-preclinical)