[article]
| Titre : |
Current neurologic treatment and emerging therapies in CDKL5 deficiency disorder |
| Type de document : |
texte imprimé |
| Auteurs : |
Heather E. OLSON, Auteur ; Carolyn I. DANIELS, Auteur ; Isabel HAVILAND, Auteur ; Lindsay C. SWANSON, Auteur ; Caitlin A. GREENE, Auteur ; Anne Marie M. DENNY, Auteur ; Scott T. DEMAREST, Auteur ; Elia PESTANA-KNIGHT, Auteur ; Xiaoming ZHANG, Auteur ; Ahsan N. MOOSA, Auteur ; Andrea FIDELL, Auteur ; Judith L. WEISENBERG, Auteur ; Bernhard SUTER, Auteur ; Cary FU, Auteur ; Jeffrey L. NEUL, Auteur ; Alan K. PERCY, Auteur ; Eric D. MARSH, Auteur ; Timothy A. BENKE, Auteur ; Annapurna PODURI, Auteur |
| Langues : |
Anglais (eng) |
| Mots-clés : |
Epilepsy/genetics/therapy Epileptic Syndromes/genetics/therapy Humans Protein Serine-Threonine Kinases/genetics Spasms, Infantile/genetics/therapy CDKL5 deficiency disorder Clinical trials Developmental encephalopathy Emerging therapies Epileptic encephalopathy Ketogenic diet Movement disorders Vagus nerve stimulator Therapeutics and Marinus Pharmaceuticals. PI of "Diagnosis and genotype-phenotype correlations in early life epilepsy and CDKL5 disorder" NINDS award (1K23NS107646). Funding for the Boston Children’s Hospital CDKL5 Center of Excellence provided by the International Foundation for CDKL5 Research. Consulting for Takeda and Ovid Therapeutics. Scott T. Demarest: site PI of clinical trials in CDD sponsored by Ovid Therapeutics and Marinus Pharmaceuticals. Consulting for Upsher-Smith and BioMarin. All remuneration has been made to his department. Elia Pestana-Knight: site PI of clinical trial in CDD sponsored by Marinus Pharmaceuticals. Co-PI of Cleveland Clinic CDD Center of Excellence established by the International Foundation for CDKL5 Research. Consultant for Marinus Pharmaceuticals. Ahsan N. Moosa: site co-investigator for clinical trials in CDD sponsored by Marinus Pharmaceuticals. Bernhard Suter: site PI of a clinical trial in CDD sponsored by Marinus Pharmaceuticals. Site PI of a clinical trial in Rett syndrome sponsored by RSRT, the investigator-initiated trial using ketamine. PI of Texas Children’s Hospital CDD Center of Excellence established by the International Foundation for CDKL5 Research. Jeffrey L. Neul: consultancy to GW Pharmaceuticals, Acadia, AveXis, Ovid Therapeutics. Data and Safety Monitoring Board for Roche, Ovid Therapeutics. Alan K. Percy: PI of the NICHD-funded Natural History Study. Site PI of clinical trials in Rett syndrome sponsored by Anavex and Acadia and the investigator-initiated trial using ketamine. Consultant with Acadia. Eric D. Marsh: site PI of clinical trial in CDD sponsored by Marinus Pharmaceuticals. Site PI for clinical trials for DS and LGS trials sponsored by Zogenix. Provides research support and clinical Center of Excellence support for the International Foundation for CDKL5 Research. Timothy A. Benke: site co-PI of clinical trials in CDD sponsored by Ovid Therapeutics and Marinus Pharmaceuticals. Consulting for AveXis, Ovid Therapeutics, Takeda, and Marinus Pharmeceuticals. All remuneration has been made to his department. Annapurna Poduri: SAB for TevardBio, no personal remuneration. Carolyn Daniels, Isabel Haviland, Lindsay Swanson, Caitlin Greene, AnneMarie M. Denny, Andrea Fidell, Cary Fu, Xiaoming Zhang, Judith L. Weisenberg: no competing interests. |
| Index. décimale : |
PER Périodiques |
| Résumé : |
BACKGROUND: CDKL5 deficiency disorder (CDD) is associated with refractory infantile onset epilepsy, global developmental delay, and variable features that include sleep, behavioral disturbances, and movement disorders. Current treatment is primarily symptom-based and informed by experience in caring for this population. METHODS: We describe medication and non-medication approaches to treatment of epilepsy and additional key neurologic symptoms (sleep disturbances, behavioral issues, movement disorders, and swallowing dysfunction) in a cohort of 177 individuals meeting criteria for CDD, 154 evaluated at 4 CDKL5 Centers of Excellence in the USA and 40 identified through the NIH Natural History Study of Rett and Related Disorders. RESULTS: The four most frequently prescribed anti-seizure medications were broad spectrum, prescribed in over 50% of individuals. While the goal was not to ascertain efficacy, we obtained data from 86 individuals regarding response to treatment, with 2-week response achieved in 14-48% and sustained 3-month response in 5-36%, of those with known response. Additional treatments for seizures included cannabis derivatives, tried in over one-third of individuals, and clinical trial medications. In combination with pharmacological treatment, 50% of individuals were treated with ketogenic diet for attempted seizure control. Surgical approaches included vagus nerve stimulators, functional hemispherectomy, and corpus callosotomy, but numbers were too limited to assess response. Nearly one-third of individuals received pharmacologic treatment for sleep disturbances, 13% for behavioral dysregulation and movement disorders, and 43% had gastrostomy tubes. CONCLUSIONS: Treatment for neurologic features of CDD is currently symptom-based and empiric rather than CDD-specific, though clinical trials for CDD are emerging. Epilepsy in this population is highly refractory, and no specific anti-seizure medication was associated with improved seizure control. Ketogenic diet is commonly used in patients with CDD. While behavioral interventions are commonly instituted, information on the use of medications for sleep, behavioral management, and movement disorders is sparse and would benefit from further characterization and optimization of treatment approaches. The heterogeneity in treatment approaches highlights the need for systematic review and guidelines for CDD. Additional disease-specific and disease-modifying treatments are in development. |
| En ligne : |
https://dx.doi.org/10.1186/s11689-021-09384-z |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 |
in Journal of Neurodevelopmental Disorders > 13 (2021)
[article] Current neurologic treatment and emerging therapies in CDKL5 deficiency disorder [texte imprimé] / Heather E. OLSON, Auteur ; Carolyn I. DANIELS, Auteur ; Isabel HAVILAND, Auteur ; Lindsay C. SWANSON, Auteur ; Caitlin A. GREENE, Auteur ; Anne Marie M. DENNY, Auteur ; Scott T. DEMAREST, Auteur ; Elia PESTANA-KNIGHT, Auteur ; Xiaoming ZHANG, Auteur ; Ahsan N. MOOSA, Auteur ; Andrea FIDELL, Auteur ; Judith L. WEISENBERG, Auteur ; Bernhard SUTER, Auteur ; Cary FU, Auteur ; Jeffrey L. NEUL, Auteur ; Alan K. PERCY, Auteur ; Eric D. MARSH, Auteur ; Timothy A. BENKE, Auteur ; Annapurna PODURI, Auteur. Langues : Anglais ( eng) in Journal of Neurodevelopmental Disorders > 13 (2021)
| Mots-clés : |
Epilepsy/genetics/therapy Epileptic Syndromes/genetics/therapy Humans Protein Serine-Threonine Kinases/genetics Spasms, Infantile/genetics/therapy CDKL5 deficiency disorder Clinical trials Developmental encephalopathy Emerging therapies Epileptic encephalopathy Ketogenic diet Movement disorders Vagus nerve stimulator Therapeutics and Marinus Pharmaceuticals. PI of "Diagnosis and genotype-phenotype correlations in early life epilepsy and CDKL5 disorder" NINDS award (1K23NS107646). Funding for the Boston Children’s Hospital CDKL5 Center of Excellence provided by the International Foundation for CDKL5 Research. Consulting for Takeda and Ovid Therapeutics. Scott T. Demarest: site PI of clinical trials in CDD sponsored by Ovid Therapeutics and Marinus Pharmaceuticals. Consulting for Upsher-Smith and BioMarin. All remuneration has been made to his department. Elia Pestana-Knight: site PI of clinical trial in CDD sponsored by Marinus Pharmaceuticals. Co-PI of Cleveland Clinic CDD Center of Excellence established by the International Foundation for CDKL5 Research. Consultant for Marinus Pharmaceuticals. Ahsan N. Moosa: site co-investigator for clinical trials in CDD sponsored by Marinus Pharmaceuticals. Bernhard Suter: site PI of a clinical trial in CDD sponsored by Marinus Pharmaceuticals. Site PI of a clinical trial in Rett syndrome sponsored by RSRT, the investigator-initiated trial using ketamine. PI of Texas Children’s Hospital CDD Center of Excellence established by the International Foundation for CDKL5 Research. Jeffrey L. Neul: consultancy to GW Pharmaceuticals, Acadia, AveXis, Ovid Therapeutics. Data and Safety Monitoring Board for Roche, Ovid Therapeutics. Alan K. Percy: PI of the NICHD-funded Natural History Study. Site PI of clinical trials in Rett syndrome sponsored by Anavex and Acadia and the investigator-initiated trial using ketamine. Consultant with Acadia. Eric D. Marsh: site PI of clinical trial in CDD sponsored by Marinus Pharmaceuticals. Site PI for clinical trials for DS and LGS trials sponsored by Zogenix. Provides research support and clinical Center of Excellence support for the International Foundation for CDKL5 Research. Timothy A. Benke: site co-PI of clinical trials in CDD sponsored by Ovid Therapeutics and Marinus Pharmaceuticals. Consulting for AveXis, Ovid Therapeutics, Takeda, and Marinus Pharmeceuticals. All remuneration has been made to his department. Annapurna Poduri: SAB for TevardBio, no personal remuneration. Carolyn Daniels, Isabel Haviland, Lindsay Swanson, Caitlin Greene, AnneMarie M. Denny, Andrea Fidell, Cary Fu, Xiaoming Zhang, Judith L. Weisenberg: no competing interests. |
| Index. décimale : |
PER Périodiques |
| Résumé : |
BACKGROUND: CDKL5 deficiency disorder (CDD) is associated with refractory infantile onset epilepsy, global developmental delay, and variable features that include sleep, behavioral disturbances, and movement disorders. Current treatment is primarily symptom-based and informed by experience in caring for this population. METHODS: We describe medication and non-medication approaches to treatment of epilepsy and additional key neurologic symptoms (sleep disturbances, behavioral issues, movement disorders, and swallowing dysfunction) in a cohort of 177 individuals meeting criteria for CDD, 154 evaluated at 4 CDKL5 Centers of Excellence in the USA and 40 identified through the NIH Natural History Study of Rett and Related Disorders. RESULTS: The four most frequently prescribed anti-seizure medications were broad spectrum, prescribed in over 50% of individuals. While the goal was not to ascertain efficacy, we obtained data from 86 individuals regarding response to treatment, with 2-week response achieved in 14-48% and sustained 3-month response in 5-36%, of those with known response. Additional treatments for seizures included cannabis derivatives, tried in over one-third of individuals, and clinical trial medications. In combination with pharmacological treatment, 50% of individuals were treated with ketogenic diet for attempted seizure control. Surgical approaches included vagus nerve stimulators, functional hemispherectomy, and corpus callosotomy, but numbers were too limited to assess response. Nearly one-third of individuals received pharmacologic treatment for sleep disturbances, 13% for behavioral dysregulation and movement disorders, and 43% had gastrostomy tubes. CONCLUSIONS: Treatment for neurologic features of CDD is currently symptom-based and empiric rather than CDD-specific, though clinical trials for CDD are emerging. Epilepsy in this population is highly refractory, and no specific anti-seizure medication was associated with improved seizure control. Ketogenic diet is commonly used in patients with CDD. While behavioral interventions are commonly instituted, information on the use of medications for sleep, behavioral management, and movement disorders is sparse and would benefit from further characterization and optimization of treatment approaches. The heterogeneity in treatment approaches highlights the need for systematic review and guidelines for CDD. Additional disease-specific and disease-modifying treatments are in development. |
| En ligne : |
https://dx.doi.org/10.1186/s11689-021-09384-z |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 |
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