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SPG4 Hereditary Spastic Paraplegia: From Etiology to Therapy
Journal article   Open access   Peer reviewed

SPG4 Hereditary Spastic Paraplegia: From Etiology to Therapy

Emanuela Piermarini and Peter W Baas
Movement Disorders, Forthcoming
Jul 2026
DOI: https://doi.org/10.1002/mds.70453
PMID: 42538614
Featured in Collection :   Research Supported by Drexel Libraries' OA Programs
url
https://doi.org/10.1002/mds.70453View
Published, Version of Record (VoR) Open Access via Drexel Libraries Read and Publish Program 2026 Open CC BY-NC-ND V4.0

Abstract

antisense oligonucleotides corticospinal tracts endoplasmic reticulum exercise therapy gene therapy hereditary spastic paraplegia intrabodies microtubule neurostimulation SPAST spastin SPG4 Hereditary Spastic Paraplegia Type 4 Hereditary Spastic Paraplegia
Hereditary spastic paraplegias (HSPs) comprise a heterogeneous group of heritable neurodegenerative disorders resulting from mutations in a wide variety of genes. HSP locomotor symptoms include lower limb weakness and spasticity that arise from progressive degeneration of corticospinal axons projecting from the motor cortex to the distal spinal cord. Ensuing gait defects typically lead to wheelchair dependence. Degeneration of other tracts can also occur, expanding the constellation of symptoms to potentially include urinary, fecal, and speech problems, as well as intellectual disability. SPG4-HSP, the most common variant, is caused by mutations in the SPAST gene, which encodes spastin, a microtubule-severing protein with membrane-related properties. Significant progress has been made in developing preclinical models for SPG4-HSP and in elucidating its mechanistic etiology. On this basis, progress is being made on developing a flexible therapeutic regimen for patients at all stages of disease progression.

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