AXV0022-hPGRN

AXV0022-hPGRN is an investigational adeno-associated virus (AAV) gene therapy designed for the treatment of frontotemporal dementia caused by mutations in the GRN gene (FTD-GRN). Developed through a collaboration between Alexion (AstraZeneca Rare Disease) and Pfizer, the therapy utilizes a novel, blood-brain barrier (BBB)-penetrant AAV capsid, AXV0022, to deliver a functional human progranulin (hPGRN) transgene via intravenous administration. This approach aims to achieve broad and deep brain distribution of the progranulin protein, thereby reversing lysosomal dysfunction, reducing neuroinflammation, and preventing the accumulation of lipofuscin and pathological lipids (such as BMP) associated with progranulin haploinsufficiency. Preclinical data in Grn knockout mice and human iPSC-derived neurons have demonstrated that AXV0022-hPGRN can restore lysosomal enzyme activity and normalize disease-relevant biomarkers at low doses.