Targeting the Gut to Improve Seizure Control in CDKL5 Deficiency Disorder (CDD)

Targeting the Gut to Improve Seizure Control in CDD

Standard anti-seizure medications have limited efficacy in seizure control in cyclin-dependent kinase-like 5 deficiency disorder (CDD).

The study will investigate whether targeting the gut-microbiota-brain axis in CDD patients can alleviate seizures and ameliorate other comorbidities.

CDD is a neurodevelopmental condition characterized by infantile-onset epilepsy, developmental delays, 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. Studies have demonstrated significant changes in gut microbial composition in animal models and between individuals with epilepsy and healthy subjects. Notably, CDD patients experience GI problems, and we discovered that they exhibit alterations in their gut microbiota compared to healthy individuals. The study will investigate whether supplementing CDD patients with alpha-lactalbum and prebiotics alone or with post-biotics can improve neurological features and modulate microbiota composition.

Inclusion Criteria:

clinical diagnosis of CDD and demonstrated CDKL5 pathogenic variant; drug-resistant seizures; ensured participation of a caregiver; willingness to sign the informed consent.

Exclusion Criteria:

organic GI disorders (i.e., food allergies, celiac disease); special diets; percutaneous endoscopic gastrostomy tube; use of antibiotics or probiotics in the previous month.