L-Serine Treatment is Associated with Improvements in Behavior, EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants
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...
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Gespeichert in:
| Autor*in: |
Krey, Ilona [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2022 |
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| Schlagwörter: |
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| Anmerkung: |
© The Author(s) 2022 |
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| Übergeordnetes Werk: |
Enthalten in: NeuroRX - Springer-Verlag, 2006, 19(2022), 1 vom: Jan., Seite 334-341 |
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| Übergeordnetes Werk: |
volume:19 ; year:2022 ; number:1 ; month:01 ; pages:334-341 |
| Links: |
|---|
| DOI / URN: |
10.1007/s13311-021-01173-9 |
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| 520 | |a 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. | ||
| 650 | 4 | |a Developmental and epileptic encephalopathy |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Epilepsy |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Precision medicine |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Targeted treatment |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Retrospective observational case series |7 (dpeaa)DE-He213 | |
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10.1007/s13311-021-01173-9 doi (DE-627)SPR047095032 (SPR)s13311-021-01173-9-e DE-627 ger DE-627 rakwb eng Krey, Ilona verfasserin (orcid)0000-0002-9168-7615 aut L-Serine Treatment is Associated with Improvements in Behavior, EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 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. Developmental and epileptic encephalopathy (dpeaa)DE-He213 Epilepsy (dpeaa)DE-He213 Precision medicine (dpeaa)DE-He213 Targeted treatment (dpeaa)DE-He213 Retrospective observational case series (dpeaa)DE-He213 von Spiczak, Sarah aut Johannesen, Kathrine M. (orcid)0000-0002-7356-3109 aut Hikel, Christiane aut Kurlemann, Gerhard aut Muhle, Hiltrud aut Beysen, Diane aut Dietel, Tobias aut Møller, Rikke S. aut Lemke, Johannes R. aut Syrbe, Steffen aut Enthalten in NeuroRX Springer-Verlag, 2006 19(2022), 1 vom: Jan., Seite 334-341 (DE-627)SPR031264964 nnns volume:19 year:2022 number:1 month:01 pages:334-341 https://dx.doi.org/10.1007/s13311-021-01173-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 19 2022 1 01 334-341 |
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10.1007/s13311-021-01173-9 doi (DE-627)SPR047095032 (SPR)s13311-021-01173-9-e DE-627 ger DE-627 rakwb eng Krey, Ilona verfasserin (orcid)0000-0002-9168-7615 aut L-Serine Treatment is Associated with Improvements in Behavior, EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 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. Developmental and epileptic encephalopathy (dpeaa)DE-He213 Epilepsy (dpeaa)DE-He213 Precision medicine (dpeaa)DE-He213 Targeted treatment (dpeaa)DE-He213 Retrospective observational case series (dpeaa)DE-He213 von Spiczak, Sarah aut Johannesen, Kathrine M. (orcid)0000-0002-7356-3109 aut Hikel, Christiane aut Kurlemann, Gerhard aut Muhle, Hiltrud aut Beysen, Diane aut Dietel, Tobias aut Møller, Rikke S. aut Lemke, Johannes R. aut Syrbe, Steffen aut Enthalten in NeuroRX Springer-Verlag, 2006 19(2022), 1 vom: Jan., Seite 334-341 (DE-627)SPR031264964 nnns volume:19 year:2022 number:1 month:01 pages:334-341 https://dx.doi.org/10.1007/s13311-021-01173-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 19 2022 1 01 334-341 |
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10.1007/s13311-021-01173-9 doi (DE-627)SPR047095032 (SPR)s13311-021-01173-9-e DE-627 ger DE-627 rakwb eng Krey, Ilona verfasserin (orcid)0000-0002-9168-7615 aut L-Serine Treatment is Associated with Improvements in Behavior, EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 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. Developmental and epileptic encephalopathy (dpeaa)DE-He213 Epilepsy (dpeaa)DE-He213 Precision medicine (dpeaa)DE-He213 Targeted treatment (dpeaa)DE-He213 Retrospective observational case series (dpeaa)DE-He213 von Spiczak, Sarah aut Johannesen, Kathrine M. (orcid)0000-0002-7356-3109 aut Hikel, Christiane aut Kurlemann, Gerhard aut Muhle, Hiltrud aut Beysen, Diane aut Dietel, Tobias aut Møller, Rikke S. aut Lemke, Johannes R. aut Syrbe, Steffen aut Enthalten in NeuroRX Springer-Verlag, 2006 19(2022), 1 vom: Jan., Seite 334-341 (DE-627)SPR031264964 nnns volume:19 year:2022 number:1 month:01 pages:334-341 https://dx.doi.org/10.1007/s13311-021-01173-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 19 2022 1 01 334-341 |
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10.1007/s13311-021-01173-9 doi (DE-627)SPR047095032 (SPR)s13311-021-01173-9-e DE-627 ger DE-627 rakwb eng Krey, Ilona verfasserin (orcid)0000-0002-9168-7615 aut L-Serine Treatment is Associated with Improvements in Behavior, EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 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. Developmental and epileptic encephalopathy (dpeaa)DE-He213 Epilepsy (dpeaa)DE-He213 Precision medicine (dpeaa)DE-He213 Targeted treatment (dpeaa)DE-He213 Retrospective observational case series (dpeaa)DE-He213 von Spiczak, Sarah aut Johannesen, Kathrine M. (orcid)0000-0002-7356-3109 aut Hikel, Christiane aut Kurlemann, Gerhard aut Muhle, Hiltrud aut Beysen, Diane aut Dietel, Tobias aut Møller, Rikke S. aut Lemke, Johannes R. aut Syrbe, Steffen aut Enthalten in NeuroRX Springer-Verlag, 2006 19(2022), 1 vom: Jan., Seite 334-341 (DE-627)SPR031264964 nnns volume:19 year:2022 number:1 month:01 pages:334-341 https://dx.doi.org/10.1007/s13311-021-01173-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 19 2022 1 01 334-341 |
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10.1007/s13311-021-01173-9 doi (DE-627)SPR047095032 (SPR)s13311-021-01173-9-e DE-627 ger DE-627 rakwb eng Krey, Ilona verfasserin (orcid)0000-0002-9168-7615 aut L-Serine Treatment is Associated with Improvements in Behavior, EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 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. Developmental and epileptic encephalopathy (dpeaa)DE-He213 Epilepsy (dpeaa)DE-He213 Precision medicine (dpeaa)DE-He213 Targeted treatment (dpeaa)DE-He213 Retrospective observational case series (dpeaa)DE-He213 von Spiczak, Sarah aut Johannesen, Kathrine M. (orcid)0000-0002-7356-3109 aut Hikel, Christiane aut Kurlemann, Gerhard aut Muhle, Hiltrud aut Beysen, Diane aut Dietel, Tobias aut Møller, Rikke S. aut Lemke, Johannes R. aut Syrbe, Steffen aut Enthalten in NeuroRX Springer-Verlag, 2006 19(2022), 1 vom: Jan., Seite 334-341 (DE-627)SPR031264964 nnns volume:19 year:2022 number:1 month:01 pages:334-341 https://dx.doi.org/10.1007/s13311-021-01173-9 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 19 2022 1 01 334-341 |
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Krey, Ilona misc Developmental and epileptic encephalopathy misc Epilepsy misc Precision medicine misc Targeted treatment misc Retrospective observational case series L-Serine Treatment is Associated with Improvements in Behavior, EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants |
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L-Serine Treatment is Associated with Improvements in Behavior, EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants Developmental and epileptic encephalopathy (dpeaa)DE-He213 Epilepsy (dpeaa)DE-He213 Precision medicine (dpeaa)DE-He213 Targeted treatment (dpeaa)DE-He213 Retrospective observational case series (dpeaa)DE-He213 |
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L-Serine Treatment is Associated with Improvements in Behavior, EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants |
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L-Serine Treatment is Associated with Improvements in Behavior, EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants |
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Krey, Ilona von Spiczak, Sarah Johannesen, Kathrine M. Hikel, Christiane Kurlemann, Gerhard Muhle, Hiltrud Beysen, Diane Dietel, Tobias Møller, Rikke S. Lemke, Johannes R. Syrbe, Steffen |
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l-serine treatment is associated with improvements in behavior, eeg, and seizure frequency in individuals with grin-related disorders due to null variants |
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L-Serine Treatment is Associated with Improvements in Behavior, EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants |
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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. © The Author(s) 2022 |
| abstractGer |
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. © The Author(s) 2022 |
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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. © The Author(s) 2022 |
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