Compositions and methods for inhibiting seizures
Inventors
Hsiao, Elaine • Yano, Jessica • Vuong, Helen • Olson, Christine
Assignees
University of California San Diego UCSD
Publication Number
US-12364717-B2
Publication Date
2025-07-22
Expiration Date
2037-12-20
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Abstract
Provided herein are methods and compositions related to treating or preventing seizures. In some aspects, provided herein are methods of treating or preventing seizures in a subject by administering to the subject a composition comprising Parabacteroides and Akkermansia bacteria.
Core Innovation
The invention provides methods and compositions for treating or preventing seizures in a subject by administering a composition comprising bacteria of the Akkermansia and Parabacteroides genera. These methods mimic the effects of a ketogenic diet by enriching specific gut microbiota, thereby conferring protection against seizures. The compositions include live bacteria such as Akkermansia muciniphila and Parabacteroides species including Parabacteroides merdae and Parabacteroides distasonis. The methods may involve depleting the gut microbiota, followed by administration of these bacteria to restore or augment seizure protection.
The problem being addressed is that epilepsy, characterized by recurrent seizures, affects 1-2% of the population and many individuals do not respond to existing anticonvulsant medications. The ketogenic diet (KD) has demonstrated efficacy in treating refractory epilepsy but has low patient retention due to difficulties with adherence and side effects. Moreover, the molecular mechanisms underlying the benefits of the KD are poorly understood, and dietary compliance is challenging. The invention aims to provide alternative methods that mimic KD effects by modulating the gut microbiota, specifically through probiotic compositions, thereby overcoming challenges associated with the KD diet.
Claims Coverage
The patent contains one independent claim focusing on a method of treating seizures by administering specific live bacteria comprising Akkermansia muciniphila and Parabacteroides merdae. The inventive features relate to the composition of bacteria, formulation, administration, and therapeutic indications.
Pharmaceutical composition comprising live Akkermansia muciniphila and Parabacteroides merdae bacteria
A method of treating seizures in a mammalian subject by administering a therapeutically effective amount of a pharmaceutical composition that comprises live Akkermansia muciniphila bacteria and live Parabacteroides merdae bacteria.
Formulation and delivery of the composition
The composition is formulated as a dry composition, suitable for oral delivery and may be provided as a pill, tablet, or capsule. The tablet or capsule may be time-released and/or enterically coated to control release within the gastrointestinal tract.
Inclusion of probiotic agents and pharmaceutically acceptable carriers
The composition may include other probiotic agents or nutrients promoting the growth of beneficial probiotic bacteria and comprises pharmaceutically acceptable carriers such as micro-crystalline cellulose, trehalose, maltodextrin, rice flour, magnesium stearate, inositol, dextrose, and sucrose.
Microbiota depletion and bacterial administration
The method may involve first depleting the subject's gut microbiota, for example, by administering antibiotics, followed by treatment with the live bacteria composition where Akkermansia muciniphila and Parabacteroides merdae bacteria are present in a 2:1 ratio.
The independent claim covers methods of treating seizures by administering a pharmaceutical composition comprising live Akkermansia muciniphila and Parabacteroides merdae bacteria, with specific formulations for delivery and options for prior microbiota depletion, addressing seizure conditions including epilepsy.
Stated Advantages
The compositions and methods mimic the effects of the ketogenic diet and confer seizure protection without requiring dietary restrictions.
They provide an alternative treatment approach that may overcome difficulties with ketogenic diet adherence and adverse side effects.
Administering specific gut bacteria can modulate seizure susceptibility, offering a novel therapeutic avenue targeting the gut microbiota rather than the central nervous system directly.
The method facilitates seizure protection even in subjects with refractory epilepsy where conventional anticonvulsants fail.
Documented Applications
Treatment or prevention of seizures, including refractory and non-refractory epilepsy.
Treatment or prevention of neurodevelopmental disorders associated with seizures, such as autism spectrum disorder, Rett syndrome, fragile X syndrome, attention deficit disorder, and attention-deficit/hyperactivity disorder.
Treatment or prevention of conditions responsive to a ketogenic diet, including Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), cancer, stroke, metabolic diseases such as obesity or diabetes, mitochondrial disorders, depression, chronic migraines, and traumatic brain injury.
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