Postdoctoral Researcher KTH - Royal Institute of Technology Solna, Stockholms Lan, Sweden
Abstract:
Background: Glucose is the primary energy source for the brain, transported via solute carrier transporter family members. SLC2A1 (GLUT1) is a crucial glucose transporter at the blood-brain barrier (BBB) and cerebrospinal fluid-blood-brain barrier (CSF-BBB), facilitating glucose uptake into the brain and cerebrospinal fluid (CSF). GLUT1 plays a critical role in maintaining glucose homeostasis within the CSF, ensuring adequate energy supply to the brain. Mutations in SLC2A1 cause GLUT1 Deficiency Syndrome (GLUT1DS), leading to seizures, microcephaly, and other neurological symptoms. The standard treatment, a ketogenic diet, has limited efficacy and long-term adverse effects, necessitating alternative therapeutic approaches1,2.
Objectives: This study aims to develop a choroid plexus organoid model to investigate glucose transport in GLUT1DS.
Methods: We generated choroid plexus organoids from patient-derived GLUT1DS iPSCs and an isogenic corrected control. Organoids were characterized by morphological and metabolic differences using biochemical assays, glucose uptake studies, and omics-based analyses.
Results: GLUT1DS choroid plexus organoids exhibited early cyst formation, reduced cerebrospinal fluid (CSF) production, and lower glucose levels compared to isogenic controls. Metabolic profiling confirmed altered glucose metabolism, which will be further validated using ¹³C-glucose uptake assays.
Conclusion: Our study establishes a clinically relevant choroid plexus organoid model to investigate glucose transport deficits in GLUT1DS. This model provides a platform for mechanistic studies, offering new insights into therapeutic strategies for GLUT1DS.
Funding Source: Wallenberg Academy Fellow grant, RED Postdoctoral Fellowships – SciLifeLab Campus Solna, Stockholm, Sweden
