Multiple pathways of disease and remedy defined
The landscape of therapeutic strategies for treating SPG4 has been laid out by the team at Drexel University in the US. This is based on their findings and hypotheses about HSP-causing SPAST mutations being responsible for both loss-of-function and toxic gain-of-function.
Mutations of the SPAST gene that encodes the microtubule-severing enzyme called spastin are the chief cause of Hereditary Spastic Paraplegia. Growing evidence indicates that pathogenic mutations functionally compromise the spastin protein and endow it with toxic gain-of-function properties.
With each of these two factors potentially relevant to disease etiology, the present article discusses possible therapeutic strategies that may ameliorate symptoms in patients suffering from SPAST-based Hereditary Spastic Paraplegia, which is usually termed SPG4-HSP.
SOURCE: Brain Sci. 2021 Aug 18;11(8):1081. doi: 10.3390/brainsci11081081. PMID: 34439700
Therapeutic Strategies for Mutant SPAST-Based Hereditary Spastic Paraplegia
1. Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19422, USA.
2. Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612, USA.