Identifying common impaired cell functions in HSP

Future drug treatments for multiple types

Genetic correction, such as with gene therapy may be possible in the future but impractical as a generalised treatment strategy.

Alan Mackay-Sim

Ideal treatments would be small molecules that are effective for people with different HSP types.

This study looked at the links between HSP types, the genes responsible and the proteins involved, identifying correlations and commonalities.

The author, Prof Alan Mackay-Sim is the Principal Investigator of the HSP Research Program that is facilitated and funded by the HSP Research Foundation.


Hereditary spastic paraplegia (HSP) is a diverse group of Mendelian genetic disorders affecting the upper motor neurons, specifically degeneration of their distal axons in the corticospinal tract. Currently, there are 80 genes or genomic loci (genomic regions for which the causative gene has not been identified) associated with HSP diagnosis. HSP is therefore genetically very heterogeneous.

Finding treatments for the HSPs is a daunting task: a rare disease made rarer by so many causative genes and many potential mutations in those genes in individual patients. Personalized medicine through genetic correction may be possible, but impractical as a generalized treatment strategy. The ideal treatments would be small molecules that are effective for people with different causative mutations. This requires identification of disease-associated cell dysfunctions shared across genotypes despite the large number of HSP genes that suggest a wide diversity of molecular and cellular mechanisms.

This review highlights the shared dysfunctional phenotypes in patient-derived cells from patients with different causative mutations and uses bioinformatic analyses of the HSP genes to identify novel cell functions as potential targets for future drug treatments for multiple genotypes.

SOURCE:  Brain Sci. 2021 Mar 22;11(3):403. doi: 10.3390/brainsci11030403. PMID: 33810178

Hereditary Spastic Paraplegia: From Genes, Cells and Networks to Novel Pathways for Drug Discovery

Alan Mackay-Sim  1

1. Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia.

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