Adolescent idiopathic scoliosis (AIS) is a prevalent spinal deformity lacking a clear understanding of its cause. Current treatment options are limited to bracing or surgery post-onset, with no preventive measures available.
A genetic analysis of a large AIS cohort of 1,701 AIS patients and 3,219 controls from the University of Hong Kong, Texas Scottish Rite Hospital for Children, and Peking Union Medical College Hospital in Beijing revealed disease-causing variants in SLC6A9, which affects glycine transporter 1 (GLYT1). T GLYT1 plays a crucial role in regulating glycine levels in the body, which is essential for proper nerve signalling in the spine. These variants reduced glycine uptake, leading to abnormal neurotransmission.
Zebrafish with mutated Slc6a9 displayed spinal curvature similar to humans with AIS. The severity of curvature was influenced by the level of functional glyt1.
Treatment with glycine receptor antagonists or sodium benzoate partially alleviated the phenotype suggesting a neuropathic origin for AIS, involving synaptic dysfunction and central pattern generators.
In a search for potential preventive therapies for adolescent idiopathic scoliosis (AIS), the researchers tested sodium benzoate, a glycine neutralizer used in clinical practice for glycine encephalopathy, on the zebrafish with the Slc6a9 mutation. Their findings indicated that sodium benzoate could moderately reduce the severity of spinal curvature in these zebrafish, suggesting its potential as a preventive therapy for AIS patients with elevated glycine levelsThis discovery offers a potential target for early diagnosis and intervention in preadolescents.
