Amlogenyx Reports Promising Preclinical Data for AM805 Gene Therapy in Alzheimer's Disease Treatment
核心洞察
Amlogenyx (搜索) announced positive preclinical results for AM805 (搜索), an AAV9 gene therapy that delivers protective protein cathepsin A (搜索) (PPCA (搜索)) to reduce amyloid (搜索) burden in Alzheimer's disease (搜索) models.
The therapy demonstrated dose-dependent amyloid (搜索) reduction in both severe and moderate mouse models, with effects comparable to or exceeding approved monoclonal antibodies.
AM805 (搜索) successfully cleared both intracellular and extracellular amyloid (搜索) across multiple administration routes, showing therapeutic effectiveness regardless of delivery method.
Amlogenyx (搜索) Inc. announced multiple positive results from preclinical studies of AM805 (搜索), an investigational AAV9 gene therapy for Alzheimer's disease (搜索) treatment. The biotechnology company's novel approach delivers protective protein cathepsin A (搜索) (PPCA (搜索)), a potent lysosomal enzyme, to reduce amyloid (搜索) burden in the brain of both severe and moderate animal models of Alzheimer's disease in young and aged mice.
The data will be presented at the AD/PDTM 2026 International Conference on Alzheimer's and Parkinson's Diseases in Copenhagen, Denmark, taking place March 19-21.
Novel Enzymatic Approach Shows Superior Amyloid Clearance
"Despite clear biology implicating amyloid (搜索) in Alzheimer's and other neurodegenerative diseases, treatments that can halt, or possibly even reverse, disease progression have eluded researchers to date," said Arjun Natesan, head of early R&D at Amlogenyx (搜索). "Amlogenyx was founded to pursue an entirely novel approach of reducing amyloid burden in the brain by delivering a potent lysosomal enzyme which would enable clearance of the intracellular burden as well as enable clearance of plaque outside of cells."
Researchers from Amlogenyx (搜索) and St. Jude Children's Research Hospital identified PPCA (搜索) as a specific lysosomal enzyme that degrades amyloid (搜索) efficiently. The team engineered AM805 (搜索), an AAV9-PPCA vector, to deliver PPCA to the central nervous system and reduce amyloid burden.
Dose-Dependent Efficacy Across Multiple Administration Routes
Study results demonstrated that all routes of dosing resulted in increased PPCA (搜索) activity and reduced amyloid (搜索)-positive brain area in a dose-dependent manner in mouse models of both severe and moderate Alzheimer's disease (搜索). The magnitude of reduction achieved was comparable to, and in some cases exceeded, that reported for approved Alzheimer's disease monoclonal antibodies.
Aβ peptide levels (4G8 positive signal) were lowered in both intracellular and extracellular compartments. PPCA (搜索) produced these reductions across multiple routes of administration, demonstrating therapeutic effectiveness regardless of how the enzyme reaches the brain.
Safety Profile Established in Non-Human Primates
The data show that the enzyme can be delivered safely to the brain in non-human primates and achieve levels of enzyme expression consistent with the therapeutic effect observed in the Alzheimer's disease (搜索) mouse models.
"We are extremely pleased to present preclinical data demonstrating that AM805 (搜索) can achieve robust amyloid (搜索) reduction in the CNS and reduce both intracellular and extracellular amyloid, even in advanced disease, underscoring its strong potential to prevent and treat this devastating and intractable disease," Natesan added.
Regulatory Timeline and Development Path
AM805 (搜索) is currently being tested in IND-enabling studies, and the company plans to pursue an Investigational New Drug (IND) application submission to the U.S. Food and Drug Administration for AM805 in 2027.
The data are being presented at the AD/PD Conference in Poster #3157, Shift #2, from March 19-21, with an ePoster and associated audio presentation available on the meeting platform.
Addressing Unmet Medical Need in Alzheimer's Treatment
In the central nervous system, amyloid (搜索) is a key driver of Alzheimer's disease (搜索), disrupting cellular homeostasis by impairing synaptic function, activating microglia, and triggering chronic neuroinflammation. AM805 (搜索) utilizes an AAV9 gene therapy vector to deliver PPCA (搜索), a lysosomal carboxypeptidase that degrades amyloid, directly to the brain.
This investigational one-time gene therapy for Alzheimer's disease (搜索) has the potential to significantly alter the course of the disease by preventing and reversing amyloid (搜索) plaque build-up and promoting neuronal health. Treatment with monoclonal antibodies to reduce amyloid has been shown to potentially slow the disease but not stop or reverse it, underscoring the need for improved treatment options.
Amlogenyx (搜索) is a subsidiary of Ultragenyx and is dedicated to developing novel gene therapy strategies to reduce amyloid (搜索) accumulation in the brain to prevent and treat diseases such as Alzheimer's disease (搜索).