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Targeting the gut to improve seizure control in CDKL5 deficiency disorder (CDD): study protocol for a single-arm,
Francesca Triva1, Elisa Borghi1, Matteo Domenico Marsiglia1
1Department of Health Sciences, University of Milan, Milan, Italy.
Insights
This study investigates targeting the gut-brain axis to treat Cyclin-dependent kinase-like 5 deficiency disorder (CDD). Supplementation with specific nutrients and sodium butyrate may reduce seizures and improve gut microbiota in CDD patients.
Area of Science:
- Neuroscience
- Microbiology
- Gastroenterology
Background:
- Cyclin-dependent kinase-like 5 deficiency disorder (CDD) is a severe neurodevelopmental condition with infantile-onset epilepsy and no current treatments.
- Epilepsy in CDD is refractory to standard anti-seizure medications, negatively impacting development.
- CDD patients exhibit gastrointestinal issues and altered gut microbiota, suggesting the gut-brain axis as a therapeutic target.
Purpose of the Study:
- To evaluate a two-step gut-microbiota-brain axis intervention in CDD patients.
- To assess the efficacy of alpha-lactalbumin, FOS, inulin, and sodium butyrate supplementation on neurological and gastrointestinal symptoms.
- To explore the impact of this intervention on gut microbiota composition and diversity.
Main Methods:
- A 24-week study involving two supplementation phases: 12 weeks of ALAC/FOS/Inulin, followed by 12 weeks of ALAC/FOS/Inulin plus Sodium Butyrate (NaB).
- Monitoring of clinical parameters including seizure frequency, sleep, and GI discomfort.
- Analysis of stool samples to characterize gut microbiome changes.
Main Results:
- The study aims to determine if the supplementation strategy can improve neurological features in CDD.
- Investigating the effects of the intervention on gut microbiota composition is a primary objective.
- Evaluating the potential of this approach to alleviate seizures and associated comorbidities.
Conclusions:
- Targeting the gut-brain axis presents a novel therapeutic strategy for CDD.
- This intervention may offer a new avenue for managing epilepsy and improving quality of life in CDD patients.
- Further research is needed to confirm the efficacy and long-term benefits of this approach.
Introduction:
Cyclin-dependent kinase-like 5 deficiency disorder (CDD) is a neurodevelopmental condition characterized by infantile-onset epilepsy, developmental delay, intellectual and motor disabilities, sleep disturbances, and cortical visual impairment. Currently, there is no treatment for CDD, and epilepsy is a prominent and severe feature of the disorder. Standard anti-seizure medications have limited efficacy in seizure control, leading to detrimental effects on cognitive and motor development in CDD. The gut-brain axis has gained attention in epilepsy research, prompted by evidence of gastrointestinal (GI) symptoms in people with epilepsy. Notably, CDD patients experience GI problems and exhibit alterations in their gut microbiota compared to healthy individuals. We propose targeting the gut-microbiota-brain axis in CDD patients to alleviate seizures and potentially ameliorate other symptoms.
Methods And Analysis:
The protocol involves a two-step treatment strategy: a 12-week supplementation with alpha-lactalbumin (ALAC), fructooligosaccharides (FOS), and inulin to reduce inflammation, followed by a 12-week supplementation with ALAC/FOS/Inulin plus Sodium butyrate (NaB), to restore the balance of the gut microbiota. Clinical parameters, including seizure frequency, sleep disturbances, and GI discomfort, will be evaluated. Stool samples will be collected to analyse the gut microbiome. Primary objectives are to determine whether supplementation with ALAC/FOS/inulin alone or in combination with NaB can improve neurological features in CDD and to explore their effects on gut microbiota composition. Our study aims to provide insights into the potential benefits of targeting the gut-brain axis in CDD and offer new therapeutic options to improve seizure control and associated comorbidities.
Ethics And Dissemination:
The study protocol was approved by the local ethics committee (CET 3, n° 4189_17.04.2024_N_bis). Study results will be disseminated by the investigators through presentations at international scientific conferences and reported in peer-reviewed scientific journals.
Clinical Trial Registration:
ClinicalTrials.gov, Identifier NCT06448663.
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