"GRIN Disorders are rare, but hope is always there."
An activity-dependent improvement in the efficacy of synaptic transmission known as long-term potentiation is mediated by NMDA receptors, a family of ionotropic glutamate receptors whose NR2 subunit is encoded by GRIN2B. GRIN2B mutations may result in altered NMDA receptor function, which may cause epileptic activity and interfere with regular neural signaling.
Our Research
This initial study will only be running knockin mice with GRIN-related Disorder with a gain-of-function (GoF) variant of: GRIN2B.
Based on RT-PCR data, our ASO-based drug specifically targets the GRIN2B gene mutation associated with autism spectrum disease and epilepsy.
Seizures of many kinds, including focal (partial) seizures and generalized seizures,
can occur in people with epilepsy linked to GRIN2B.
Apart from epilepsy, GRIN2B mutations are frequently linked to neurodevelopmental issues such as intellectual disability and autism spectrum disorders. In almost half of cases of neurodevelopmental disease associated with GRIN2B, there are recurrent seizures, or epilepsy. Impaired social interaction and communication are hallmarks of autism spectrum disorder, which affects about 25% of those who are impacted.
In addition to being hyperactive, impulsive, or quickly distracted, affected people can also be regarded as excessively gregarious. This illness can also cause trouble sleeping.
The predicted incidence per 100,000 births is 5.91, meaning that out of every 100,000 babies born, about 6 babies would have a de novo variant in GRIN2B (6 in 1 lakh).
Neuronal development progresses through several steps, coinciding with the period of high expression of GluN2B. During the early stages of development, GluN2B levels progressively increase, while GluN2A levels are low (yellow). As neurons mature, GluN2A levels increase and ultimately surpass GluN2B expression (blue). GluN2B has been proposed to play a role in neuronal differentiation, dendrite morphogenesis, synaptogenesis, circuit refinement, and synaptic plasticity.
Diagnosis of GRIN2B-related disorders
Genetic testing is required to diagnose a GRIN2B-related disorder.
Electroencephalogram (EEG) to look for evidence of abnormal brain activity and seizures
Magnetic resonance imaging (MRI) to look for changes in brain structure. Although most children with GRIN2B-related disorders do not have developmental or structural differences in their brains, approximately 15% of individuals with GRIN2B-related disorders have extensive polymicrogyria.
Treatment for GRIN2B-related disorders
Treatment for GRIN2B-related disorders will depend on the type and severity of the seizures and associated neurological features:-
Epilepsy Neurogenetics Initiative (ENGIN) providers have experience in the management of epilepsy in children with GRIN2B-related disorders.
ENGIN providers have been involved in early efforts to develop targeted treatment approaches for GRIN2B-related disorders.
A different set of medications, known as “rescue therapies,” may be given to help stop or shorten clusters of seizures when they occur.
Implantable devices such as vagus nerve stimulation (VNS) or responsive neurostimulation (RNS) may be considered when medications are not effective in controlling seizures.
Dietary therapy, such as the ketogenic diet, may be helpful in some cases.
Resources for GRIN2B-related disorders
