Disease State

Program Overview

GRIN Therapeutics has its roots in working with patients, caregivers, and families of people living with developmental and epileptic encephalopathies. Our connections with those living with these conditions continues to inform the design and structure of our clinical development programs. We believe in putting people at the center of everything we do.

NMDA Receptors in Neurodevelopmental Disorders

Neurotransmission in the brain can either activate (excitatory) or quiet (inhibitory) neural signals. The brain functions like a finely tuned instrument and keeping a healthy balance between excitatory and inhibitory signals is essential for proper brain function. NMDA receptors are a key part of excitatory neurotransmission and play an important role in maintaining this balance. These receptors have been studied in connection with several neurodevelopmental disorders, and early research suggests they may contribute to the underlying mechanisms of these conditions.

Imagine the NMDA receptor in the cell surface like a gate in a fence. If there is a change in the number of receptors (gates), or in the ability of that gate to open, it could change the flow of sodium and calcium (chickens) through the gate and increase the number of chickens that are able to cross the fence.

Our Clinical Trial Program

GRIN Therapeutics is currently developing radiprodil, an investigational negative allosteric modulator of the GluN2B (NR2B) subunit of the NMDA receptor, in neurodevelopmental disorders including GRIN-related neurodevelopmental disorder, Tuberous Sclerosis Complex (TSC), and Focal Cortical Dysplasia Type II (FCDII).

For more information on our currently enrolling studies:

For GRIN-NDD:
- ClinicalTrials.gov, NCT07224581
For TSC and FCDII:
- Astroscape Study
- ClinicalTrials.gov, NCT06392009

About GRIN-NDD

GRIN-related neurodevelopmental disorder (GRIN-NDD) was first classified in 2010 and is a rare, genetically defined pediatric condition caused by mutations in a group of genes known as “GRIN” genes that includes GRIN1, GRIN2A, GRIN2B, and GRIN2D. These genes encode the GluN1 (NR1), GluN2A (NR2A), GluN2B (NR2B), and GluN2D (NR2D) subunits of the NMDA receptor. Symptoms of GRIN-NDD can present as early as infancy, but a diagnosis is often delayed until around age two or later, when developmental milestones are missed. Genetic testing can confirm the diagnosis. Most people living with GRIN-NDD experience significant disabilities that require ongoing supervision. Currently, there are no FDA-approved therapies that directly target the root cause of GRIN-NDD.

Additional information about GRIN-NDD is available from international organizations including:

GRIN2B Foundation

CureGRIN

GRIN Europe

People with diagnosed with GRIN-NDD who would like to learn more about their specific GRIN variant can explore the GRIN portal:

GRIN portal at the Broad institute

About TSC

Tuberous Sclerosis Complex (TSC) is a multi-system genetic disorder caused by mutations in the TSC1 or TSC2 genes. These mutations lead to the growth of non-cancerous tumors in various organs, including the brain, eyes, heart, kidneys, skin and lungs. When the brain is affected, individuals may experience seizures, developmental delays, autism spectrum disorder, and a range of behavioral and cognitive challenges. The type and severity of symptoms can vary widely from person to person.

Research has shown increased NMDA receptor activity – especially overexpression of GluN2B –in brain tissue from TSC patients, suggesting a role in the underlying disease mechanism. TSC is most common genetic cause of epilepsy and autism. Although some patients respond to antiseizure medications, only about one-third become seizure-free[1]. In addition to seizures, individuals with TSC often experience other symptoms such as anxiety, aggression sleep disturbances, and sensory processing issues. Currently, there are no approved treatments that target the underlying cause of TSC.

More information about TSC is available from international organizations including:

TSC Alliance

European TSC Association

About FCDII

Focal Cortical Dysplasia Type II (FCDII) is a rare neurodevelopmental disorder caused by abnormal brain formation during fetal development. In some cases, genetic factors may contribute to the condition. The disorganized development of brain cells and layers leads to a high risk of seizures and impaired brain function. Research suggests that seizure activity and other symptoms may be partly driven by changes in NMDA receptor activity, including increases in GluN2B subunit expression.

Most individuals with FCDII are diagnosed in early childhood after symptoms appear, with magnetic resonance imaging (MRI) often used to confirm the diagnosis. Antiseizure medications can help manage symptoms for some, but many individuals with FCDII experience drug-resistant seizures. In fact, only about one in five individuals achieve sufficient seizure control with medication alone. Currently, there are not approved therapies that target the underlying cause of FCDII or its specific disease mechanisms, highlighting the need for more effective and targeted treatment options.