Nutritional Formulation for Patients with Angelman Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study of...

Area of Science:

• Neurology
• Genetics
• Nutritional Science

Background:

• Angelman syndrome (AS) patients often have refractory seizures managed with low glycemic index therapy.
• These diets are difficult to implement and impact quality of life.
• Exogenous ketone formulations (KF) may offer benefits in AS, even without ketosis biomarkers.

Purpose of the Study:

• To compare an exogenous medical food ketone formulation (KF) with placebo for dietary management in Angelman syndrome (AS).

Main Methods:

• A 16-week randomized, double-blind, placebo-controlled, crossover trial involving 13 participants (ages 4-11) with AS.
• Evaluated safety, tolerability, seizure burden, cortical irritability, cognition, mobility, sleep, and developmental staging.
• Primary outcomes: study retention and adherence; secondary outcomes: various clinical assessments.

Main Results:

• One participant discontinued due to formulation adherence issues.
• KF consumption improved stool consistency (P=0.0027) and showed trends toward decreased EEG delta frequency power.
• Improvements were noted in fine motor skills (Vineland-3) and potential changes in frontal memory response via event-related potentials.

Conclusions:

• Exogenous KF appears safe for Angelman syndrome (AS) patients.
• Further research is required to establish the efficacy of exogenous ketones as a nutritional strategy for AS.
• Clinical trial registered at clinicaltrials.gov (NCT03644693).