Why the study?
Targeting astrocyte glutamate release represents a promising therapeutic strategy in hyper-glutamatergic brain conditions without directly blocking glutamatergic neurotransmission.
Astrocyte-targeted viral vectors expressing inhibitory nanobodies against VGLUT can cross the blood-brain barrier and achieve cell-specific expression, offering a potential new gene therapy approach for hyper-glutamatergic brain conditions.
Targeting astrocyte glutamate release offers a promising strategy in hyper-glutamatergic CNS conditions; leaves open validation of selective modulators in clinical trials.
Astrocytes, the main Central Nervous System (CNS) glial cell type, actively release transmitters, including glutamate, and thereby participate in physiological brain information processing. However, dysregulated transmitter release from astrocytes can contribute to CNS disease pathogenesis and progression. Therefore, targeting astrocyte glutamate release is a promising new therapeutic strategy in hyper-glutamatergic brain conditions, as it does not directly block glutamatergic neurotransmission. Basing on the evidence that astrocytes express Vesicular Glutamate Transporters (VGLUT), in collaboration with other NCCR TransCure partners, we developed an innovative approach for astrocyte-selective delivery of nanobodies inhibiting VGLUT. We inserted the anti-VGLUT nanobody constructs in astrocyte-directed viral vectors that were administered peripherally, crossed the blood-brain-barrier and led to successful cell-specific CNS-wide expression of the nanobodies.
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Ceglia et al. (2022) studied this question.
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