biostudies-literatureUnknown33(12)Quinlan MAPaul G Allen Family FoundationAllen InstituteBioMarin Pharmaceutical IncSYNGAP1-related disorders (SRDs) are rare neurodevelopmental conditions characterized by severe neurological symptoms, including epilepsy, motor impairment, and cognitive dysfunction. Current treatment options are limited, with patients relying on a cocktail of medications to manage the diverse symptoms but that do not address the underlying pathology. SRDs are primarily caused by haploinsufficiency of the SYNGAP1 gene, which encodes the synaptic scaffolding and signaling protein, SynGAP. We developed a gene supplementation strategy to deliver broad neuronal expression of human SYNGAP1 via an adeno-associated virus (AAV). Driven by the pan-neuronal SYNAPSIN I promoter, SYNGAP1 delivery alleviated several disease phenotypes in a Syngap1 heterozygous mouse model, including epileptiform activMolecular therapy : the journal of the American Society of Gene Therapy6398-6414https://www.ebi.ac.uk/biostudies/studies/S-EPMC12703155biostudies-literatureAAV delivery of full-length SYNGAP1 rescues epileptic and behavioral phenotypes in a mouse model of SYNGAP1-related disorders.PMC12703155Levi BPChristian RJLiu JLeedy JMRonellenfitch KGroce ELQuinlan MAGudsnuk KMLopez MEBhowmik RReding MGuo RWright VMich JKBishaw YMLuber EMLiang EIchida JKMartinez RADaigle TLClark AGGore BBLein ESfalseAAV delivery of full-length SYNGAP1 rescues epileptic and behavioral phenotypes in a mouse model of SYNGAP1-related disorders.SYNGAP1-related disorders (SRDs) are rare neurodevelopmental conditions characterized by severe neurological symptoms, including epilepsy, motor impairment, and cognitive dysfunction. Current treatment options are limited, with patients relying on a cocktail of medications to manage the diverse symptoms but that do not address the underlying pathology. SRDs are primarily caused by haploinsufficiency of the SYNGAP1 gene, which encodes the synaptic scaffolding and signaling protein, SynGAP. We developed a gene supplementation strategy to deliver broad neuronal expression of human SYNGAP1 via an adeno-associated virus (AAV). Driven by the pan-neuronal SYNAPSIN I promoter, SYNGAP1 delivery alleviated several disease phenotypes in a Syngap1 heterozygous mouse model, including epileptiform activ2025-01-01T00:00:00Z2025 Dec2026-07-15T06:15:22.227Z2026-06-30T03:21:44.44ZS-EPMC127031554098833810.1016/j.ymthe.2025.09.040