ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2022
L-Serine Treatment is Associated with Improvements in Behavior, EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 47 citations in OpenAlex.
- AST-001 versus placebo for social communication in children with autism spectrum disorder: A randomized clinical trial.Psychiatry and clinical neurosciences · 2025Trial
- Developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep: Pathophysiological insights and treatment options.Epilepsia · 2026Review
- Article
- Integrated proteomic and single-cell transcriptomic profiling elucidates immunomodulatory effects of L-serine in autism spectrum disorder.Scientific reports · 2026Article
- Gene Portals: A Framework for Integrating Clinical, Functional, and Structural Evidence into Rare Disease Variant Classification.medRxiv : the preprint server for health sciences · 2026Article
- Context-dependent NMDA receptor dysfunction predicts seizure treatment in mice with human GluN1 variant.iScience · 2026Article
- GRIN2A null variants confer a high risk for early-onset schizophrenia and other mental disorders and potentially enable precision therapy.Molecular psychiatry · 2026Article
- Clinical and genetic landscape of epilepsies with absence seizures and single-gene etiology.Epilepsia · 2026Article
- Clinical and Molecular Genetic Characterization of Landau Kleffner Syndrome: An Observational Cohort and Experimental Study.Annals of neurology · 2025Observational
- Editorial - Patient perspectives on new therapies for genetic diseases.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025Article
- Blueprint for clinical N-of-1 strategies with off-label precision treatments in monogenic epilepsies.Orphanet journal of rare diseases · 2025Review
- Clinical utility of genome sequencing in autism: illustrative examples from a genomic research study.Journal of medical genetics · 2025Article
- Precision therapies for genetic epilepsies in 2025: Promises and pitfalls.Epilepsia open · 2025Article
- Precision Therapeutics in Lennox-Gastaut Syndrome: Targeting Molecular Pathophysiology in a Developmental and Epileptic Encephalopathy.Children (Basel, Switzerland) · 2025Review
- Nootropic foods in neurodegenerative diseases: mechanisms, challenges, and future.Translational neurodegeneration · 2025Review
- Spermidine Treatment Improves GRIN2B Loss-Of-Function, A Primary Disorder of Glutamatergic Neurotransmission.Journal of inherited metabolic disease · 2025Article
- L-serine treatment in a patient with refractory epilepsy due to a GRIN2A missense mutation.Acta neurologica Belgica · 2024Article
- Solving the Etiology of Developmental and Epileptic Encephalopathy with Spike-Wave Activation in Sleep (D/EE-SWAS).Annals of neurology · 2024Article
- Developmental and epileptic encephalopathies.Nature reviews. Disease primers · 2024Review
- Channelopathies in epilepsy: an overview of clinical presentations, pathogenic mechanisms, and therapeutic insights.Journal of neurology · 2024Review
Corrections and comments
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Authors and funding
11 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pathogenic missense variants in GRIN2A and GRIN2B may result in gain or loss of function (GoF/LoF) of the N-methyl-D-aspartate receptor (NMDAR). This observation gave rise to the hypothesis of successfully treating GRIN-related disorders due to LoF variants with co-agonists of the NMDAR. In this respect, we describe a retrospectively collected series of ten individuals with GRIN2A- or GRIN2B-related disorders who were treated with L-serine, each within an independent n-of-1 trial. Our cohort comprises one individual with a LoF missense variant with clinical improvements confirming the above hypothesis and replicating a previous n-of-1 trial. A second individual with a GoF missense variant was erroneously treated with L-serine and experienced immediate temporary behavioral deterioration further supporting the supposed functional pathomechanism. Eight additional individuals with null variants (that had been interpreted as loss-of-function variants despite not being missense) again showed clinical improvements. Among all nine individuals with LoF missense or null variants, L-serine treatment was associated with improvements in behavior in eight (89%), in development in four (44%), and/or in EEG or seizure frequency in four (44%). None of these nine individuals experienced side effects or adverse findings in the context of L-serine treatment. In summary, we describe the first evidence that L-serine treatment may not only be associated with clinical improvements in GRIN-related disorders due to LoF missense but particularly also null variants.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.