AAV-Parkin

AAV-Parkin is an adeno-associated virus (AAV) gene therapy candidate designed for the treatment of early-onset familial Parkinson’s disease (EOPD) caused by biallelic loss-of-function mutations in the *PRKN* gene. The therapy utilizes an AAV vector to deliver a functional human *PARKIN* transgene, which encodes the Parkin E3 ubiquitin ligase. Parkin is a critical component of the PTEN-induced kinase 1 (PINK1)-Parkin pathway, which serves as a cellular stress response to identify and mark damaged mitochondria for degradation (mitophagy). In patients with *PRKN* mutations, the absence of functional Parkin leads to the accumulation of damaged mitochondria and increased oxidative stress, resulting in neurodegeneration in the substantia nigra. AAV-Parkin aims to restore Parkin expression and activate the mitophagy pathway to prevent or slow disease progression. Preclinical studies have demonstrated the restoration of phospho-ubiquitin (pUb Ser65) signaling in Parkin-deficient cells and dose-dependent transgene expression in rodent models using Spark Therapeutics' proprietary capsids.

Other names

AAV-PRKN