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.