Therapeutic strategies for SPG4

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.

(L to R) Peter Baas, Gerardo Morfini, Liang Qiang


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

Neha Mohan  1 Liang Qiang  1 Gerardo Morfini  2 Peter W Baas  1

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.


    1. Editor’s note: Right now there is nothing available to fix the condition, however there is quite a bit that can be done to help manage the symptoms, maximise functionality and quality of life. How to best manage HSP is different for different people. The aim is to be fit, flexible, achieve and maintain target body weight, and maximise mobility. People who can help with assessment, program development, monitoring and care include neurologists, rehab physicians and allied health professionals including physical therapists (especially those with specialist neurological training) occupational therapists, podiatrists and occasionally others such as urologists and psychologists. It all depends on the individual as to what’s needed and what works best. Click on the ‘Living with HSP’ banner on the website homepage for hundreds of articles on all aspects of the topic or use the Search box to bring up articles on specific topics of interest.

  1. I sent in a skin biopsy and blood. I have SPG4. I hope you got this! Praying there will be a cure soon! I was diagnosed at 31 and now 49. I would love to enjoy my life again. Many years have been taken away. Thanks for doing research! ❤🙏

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