Patient-Derived Stem Cell Models in SPAST HSP: Disease Modelling and Drug Discovery

Gautam Wali; Carolyn M Sue; Alan Mackay-Sim

doi:10.3390/brainsci8080142

Patient-Derived Stem Cell Models in SPAST HSP: Disease Modelling and Drug Discovery

Brain Sci. 2018 Jul 31;8(8):142. doi: 10.3390/brainsci8080142.

Authors

Gautam Wali¹, Carolyn M Sue², Alan Mackay-Sim³

Affiliations

¹ Department of Neurogenetics, Kolling Institute of Medical Research, The University of Sydney, Sydney, NSW 2065, Australia. gautam.wali@sydney.edu.au.
² Department of Neurogenetics, Kolling Institute of Medical Research, The University of Sydney, Sydney, NSW 2065, Australia. carolyn.sue@sydney.edu.au.
³ Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia. a.mackay-sim@griffith.edu.au.

Abstract

Hereditary spastic paraplegia is an inherited, progressive paralysis of the lower limbs first described by Adolph Strümpell in 1883 with a further detailed description of the disease by Maurice Lorrain in 1888. Today, more than 100 years after the first case of HSP was described, we still do not know how mutations in HSP genes lead to degeneration of the corticospinal motor neurons. This review describes how patient-derived stem cells contribute to understanding the disease mechanism at the cellular level and use this for discovery of potential new therapeutics, focusing on SPAST mutations, the most common cause of HSP.

Keywords: SPAST; SPG4; microtubule; neurodegeneration; organelle transport; peroxisome; spastic paraplegia; spastin.

Publication types

Review