New cellular imaging‐based method to distinguish the SPG4 subtype of hereditary spastic paraplegia

Abstract

Hereditary spastic paraplegia (HSP) is a genetic motoneuron disease characterized by lower limb spasticity resulting from slowly progressive degeneration of long corticospinal axons [1]. Thus far, more than 85 distinct spastic paraplegia genes (SPG) have been identified. Proteins encoded by the SPG genes have diverse functions in several interrelated cellular pathways, such as microtubule (MT) dynamics, intracellular trafficking, mitochondrial functions, fatty acid and phospholipid metabolism, endoplasmic reticulum shaping and stress response, and autophagy [2]. Mutations in the SPG4/SPAST gene account for 40%-60% of autosomal dominant HSPs with about 86%

Outcome Measures and Biomarkers for Clinical Trials in Hereditary Spastic Paraplegia: A Scoping Review

“…More recently, two groups used different approaches to differentiate individuals with HSP- SPAST (SPG4) from healthy controls by analyzing peripheral blood mononuclear cells. Our group demonstrated reduced levels of acetylated α-tubulin seen on flow cytometry [ 93 ], while another group showed increased distance between cell and nucleus centroids on automated image analysis [ 94 ]. Both studies used surrogate markers of microtubule dysfunction based on the known role of spastin in regulating microtubule dynamics in HSP- SPAST .…”