Gene replacement therapy for hereditary spastic paraplegia type 47
Mutations in the adaptor protein complex 4 β1 subunit (AP4B1) gene has been linked to a neurological disorder, Spastic paraplegia 47 (SPG47) .
The researchers developed a gene replacement therapy by restoring AP-4 complex function in an SPG47 mouse model.
Measurement of plasma neurofilament light chain levels was used as a biomarker of effective dosing in postnatal mouse treatment.
A single AAV9/hAP4B1 administration into the CSF of adult mice reduces the severity of some key disease features, including: ATG9A mislocalization, the presence of calbindin-positive spheroids, and motor dysfunction.
The researchers found no significant adverse events with the GLP safety and biodistribution studies and they filed an investigational new drug application to initiate clinical trials in SPG47 patients.
https://www.embopress.org/doi/full/10.1038/s44321-024-00148-5
