Background

Synaptic GTPase activating protein (SynGAP1) mutations cause MRD5 childhood intellectual disability with epilepsy and autism. The incidence of SynGAP1 loss-of-function mutations is estimated to be 1-4/10,000. There is no cure for MRD5, but therapy is usually related to the treatment of epilepsy symptoms and behavioural management for autism spectrum disorder.

The SynGAP1 gene produces multiple protein isoforms and SynGAP1 haploinsufficiency causes disease but whether a particular protein isoform is important is unknown. SynGAP1 is an important component of the postsynaptic density of CNS synapses. In experimental systems, SynGAP1 mutations cause an abnormal neuronal morphology and increased electrical synaptic activity.

Technology Overview

Researchers at The University of Sheffield are creating SynGAP1 gene therapy to treat MRD5. Initially, they are testing lentiviral gene therapy vectors of the different SynGAP1 isoforms for efficacy in vitro. To address the relatively large size of the SynGAP1 gene, the team are developing size‑optimised dual & single vector constructs that will be suitable for adaptation to AAV gene therapy.

Benefits

Potentially the first disease‑modifying therapy for MRD5.

Applications

Specific for MRD5 patients.

Opportunity

The University is looking for collaborative partners, investment and funding to advance the SynGAP1 research programme.

Gene Therapy for SynGAP1 Deficiency

IP Status

Seeking