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Hereditary spastic paraplegia: from diagnosis to emerging therapeutic approaches.

Accepted version
Peer-reviewed

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Type

Article

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Authors

Shribman, Samuel 
Crosby, Andrew H 
Houlden, Henry 
Warner, Thomas T 

Abstract

Hereditary spastic paraplegia (HSP) describes a heterogeneous group of genetic neurodegenerative diseases characterised by progressive spasticity of the lower limbs. The pathogenic mechanism, associated clinical features, and imaging abnormalities vary substantially according to the affected gene and differentiating HSP from other genetic diseases associated with spasticity can be challenging. Next generation sequencing-based gene panels are now widely available but have limitations and a molecular diagnosis is not made in most suspected cases. Symptomatic management continues to evolve but with a greater understanding of the pathophysiological basis of individual HSP subtypes there are emerging opportunities to provide targeted molecular therapies and personalised medicine.

Description

Keywords

Genetic Predisposition to Disease, Genetic Therapy, High-Throughput Nucleotide Sequencing, Humans, Mutation, Precision Medicine, Spastic Paraplegia, Hereditary

Journal Title

Lancet Neurol

Conference Name

Journal ISSN

1474-4422
1474-4465

Volume Title

18

Publisher

Elsevier BV
Sponsorship
Medical Research Council (MR/L023784/2)
Medical Research Council (MR/L023784/1)