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Review | Open Access

Advances in STXBP1 encephalopathy research and translational opportunities

Yi Zhenga,1( ), Feiyang Lia,1, Jingming Shib( )
Laboratory of Ageing Research, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China
Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang 712082, Shaanxi, China

1 These authors contributed equally.

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Graphical Abstract

STXBP1 encephalopathy is caused by disease-causing mutations in the STXBP1 gene.

Abstract

STXBP1 encephalopathy (STXBP1-E) is a rare neurodevelopmental disorder that includes epilepsy; it is caused by de novo STXBP1 mutations. In clinical settings, pharmaceutical interventions to treat STXBP1-E predominantly concentrate on seizure control. However, effective treatments for seizure recurrence, treatment resistance, and common comorbidities remain scarce. Patients with STXBP1-E display a wide range of pathogenic variations that manifest as loss-of-function, gain-of-function, or dominant-negative effects. However, recent studies have primarily investigated the pathogenic mechanisms resulting from loss-of-function mutations using STXBP1 haploinsufficiency models. This approach fails to accurately assess the impact of disease-causing mutations. Moreover, to evaluate new syntaxin-binding protein 1 (STXBP1)-targeting drugs, novel models that incorporate disease-causing mutations or even the genetic backgrounds of patients are needed. Here, we discuss the clinical symptoms of STXBP1-E and the relationship between this disorder and STXBP1 mutations. We also review recent progress toward understanding the biological function of STXBP1 and its deficiency-induced cellular defects. We then discuss recent discoveries concerning the pathogenesis of STXBP1-E and the limitations and challenges associated with the current research model. Additionally, we underscore the value of leveraging stem cell technology to study the pathogenic mechanisms of STXBP1-E, and review stem cell transplantation as a potential approach for treating this disorder. We also discuss potential future research directions that need to be resolved.

Keywords

STXBP1HaploinsufficiencyNeurotransmitter releaseEpilepsyNeurodevelopmental disorder

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Journal of Neurorestoratology
Volume 12 Issue 3,
September 2024
Article number: 100134
DOI: 10.1016/j.jnrt.2024.100134
Cite this article:
Zheng Y, Li F, Shi J. Advances in STXBP1 encephalopathy research and translational opportunities. Journal of Neurorestoratology, 2024, 12(3): 100134. https://doi.org/10.1016/j.jnrt.2024.100134

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Received: 11 March 2024
Revised: 22 April 2024
Accepted: 08 May 2024
Published: 10 June 2024
© 2024 The Author(s).

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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