Screening for drugs that mobilize ATG9A from the Golgi as a potential therapy for SPG type 47, 50, 51 and 52 diseases

National Center For Advancing Translational Sciences

Investigators

Abstract

This project aims to identify small molecules that mobilize ATG9A from the Golgi complex in AP-4-deficient cells as a potential therapy for AP-4-deficiency syndrome. In addition, mobilization of ATG9A from the Golgi complex is hypothesized to enhance autophagy in cells that are not deficient in ATG9A, a property that could be explored for the treatment of neurodegenerative disorders caused by accumulation of autophagy substrates, such as protein aggregates in Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis and others. During this period, NCATS team has screened the NPC drug collection against human (WT) and patient fibroblast (AP4-HSP) cell lines using a high-content assay. Hits were identified capable of mobilizing ATG9A without cytotoxicity, and this activity is currently being validated. Additional screening work is currently in progress.