Project Overview

The field of research into Hereditary Spastic Paraplegia (HSP) has utilized various experimental models, such as cell cultures, fruit flies, and rodents, to investigate SPG4 and trial potential therapies. However, existing mouse models either carry a mutated human SPAST gene alongside their own genes or lack their own SPAST genes entirely, failing to fully replicate the human condition where both SPAST genes are affected.

Dr. Peter Baas aims to bridge this gap by developing a novel mouse model, fully funded by The Lilly and Blair Foundation. This model will replace the mouse SPAST genes with human SPAST genes, including all essential components like introns and exons. Crucially, one of these human SPAST genes will harbor a severe mutation identical to that found in children with aggressive early-onset SPG4.

This new mouse model - with an anticipated delivery by July 2025 - promises to significantly advance therapeutic development. It will facilitate the testing of potential treatments such as antisense oligonucleotides, gene therapy vectors, antibodies, and small molecule inhibitors. Success in these studies could pave the way for transformative treatments for SPG4 patients in the future. Your support can help accelerate this critical research towards finding a cure for childhood-onset SPG4.