VEGF-Mimetic Supramolecular Nanoparticles for Treating Spinocerebellar Ataxia Type 1

脊髓小脑性共济失调1型（SCA1）是一种进行性神经退行性疾病

Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease caused by a polyglutamine expansion in the protein ATXN1. In the course of delineating early mechanisms underlying neurodegeneration, we made the unexpected discovery that ATXN1 directly regulates the expression of the angiogenic and neurotrophic cytokine VEGF and that VEGF levels are abnormally low in the SCA1 mouse brain with pathologic consequences. We have since discovered that delivering recombinant VEGF is therapeutic in the well-characterized SCA1 knock-in mouse (SCA1154Q/2Q; Q=glutamine), the most precise existing mouse model of SCA1. However, there are several challenges with developing recombinant VEGF as a therapy. Here we propose to build upon our recent work developing a VEGF-mimetic particle that could be readily synthesized with a greater potential to engage VEGF receptors in both neurons and endothelial cells to maintain neurovascular health in SCA1. The goal is to engineer a first-in-class nanotherapy for SCA1.