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Lennox-Gastaut syndrome

Lennox-Gastaut syndrome (LGS) is a rare but severe form of childhood epilepsy, characterized by a triad of multiple seizure types, characteristic electroencephalogram (EEG) findings, and intellectual impairment

Prevalence

15/100,000

49,650

US Estimated

77,025

Europe Estimated

Age of Onset

Infancy

ICD-10

G40.81

Inheritance

Autosomal dominant

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Autosomal recessive

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Mitochondrial/Multigenic

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X-linked dominant

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Multigenic or multifactor

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5 Facts you should know

FACT

1

Lennox-Gastaut syndrome (LGS) is a pediatric epilepsy syndrome characterized by multiple seizure types; mental retardation or regression.

FACT

2

The hallmark signs of LGS are “drop seizures”, which may occur several times/day.

FACT

3

The mean age at epilepsy onset is 26-28 months.

FACT

4

LGS has characteristic abnormal findings on electroencephalogram (EEG), with paroxysms of fast activity and generalized slow spike-and-wave discharges (1.5-2 Hz).

FACT

5

A significant correlation exists between age of onset of seizures and mental deterioration.

Lennox-Gastaut Syndrome is also known as...

Lennox-Gastaut Syndrome

Childhood epileptic encephalopathy; Encephalopathy of childhood; LGS

What’s your Rare IQ?

Which of the following is not a “classic” symptom typical of patients with Lennox-Gastaut syndrome (LGS)?

Common signs & symptoms

EEG with focal sharp slow waves

Encephalopathy

Intellectual disability

Mental deficiency, mental retardation, nonspecific mental-retardation

Abnormality of brainstem morphology

Abnormal shape of brainstem

Aggressive behavior

Atonic seizure

Current treatments

Rufinamide(Brand name: Banzel)

Manufactured by Eisai Medical Research, Inc.
FDA-approved indication: Adjunctive therapy of seizures associated with Lennox-Gastaut syndrome.

Cannabidiol(Brand name: Epidiolex)

Manufactured by GW Pharma Ltd.
FDA-approved indication: June 2018, cannabidiol (Epidiolex) was approved for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) in patients 2 years of age and older. Sept 2018, the DEA (US Drug Enforcement Agency) placed Epidolex in schedule V of Controlled Substance Act. However, availability may be dependent on laws of individual States.

Felbamate(Brand name: Felbatol®)

Manufactured by Meda Pharmaceuticals Inc.
FDA-approved indication: As adjunctive therapy in the treatment of partial and generalized seizures associated with the Lennox-Gastaut syndrome in children.

Perampanel(Brand name: Fycompa)

Manufactured by Eisai, Inc.
FDA-approved indication: Treatment of Lennox-Gastaut Syndrome. Treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy 12 years of age and older and as adjunctive therapy for the treatment of primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older.

Lamotrigine(Brand name: Lamictal®)

Manufactured by Glaxo Wellcome Research and Development. FDA-approved indication: Adjunctive treatment of Lennox-Gastaut syndrome in pediatric and adult patients.

Topiramate(Brand name: Topamax®)

Manufactured by Ortho-McNeil Neurologics
FDA-approved indication: As adjunctive therapy in patients two years and older with seizures associated with Lennox-Gastaut syndrome.

Fenfluramine (Brand name: Fintepla®)

Manufactured by Zogenix International Limited.
The mechanisms by which fenfluramine exerts its therapeutic effects in the treatment of seizures associated with LGS are unknown. Fenfluramine and the metabolite, norfenfluramine, increase extracellular levels of serotonin through interaction with serotonin transporter proteins, and exhibit agonist activity at serotonin 5HT-2 receptors.

Top Clinical Trials

TitleDescriptionPhasesStatusInterventionsMore Information
A Study of Soticlestat as an Add-on Therapy in Children, Teenagers, and Adults With Lennox-Gastaut SyndromeThe aims of the study are to learn if soticlestat, when given as add-on therapy, reduces the number of major motor drop seizures in children, teenagers, and adults with Lennox-Gastaut Syndrome. Further, to assess the safety profile of soticlestat when given in combination with other therapies.
Participants will receive their standard anti-seizure therapy, plus either tablets of soticlestat or placebo. A placebo looks just like soticlestat but will not have any medicine in it. Participants will take soticlestat or placebo for 16 weeks, followed by a gradual dose reduction for 1 week. Then, participants will be followed up for 2 weeks.
Phase 3RecruitingDrug: Soticlestat|Drug: PlaceboMore Info
A Phase 2, Prospective, Interventional, Open-Label, Multi-Site, Extension Study to Assess the Long-Term Safety and Tolerability of TAK-935 (OV935) as Adjunctive Therapy in Patients With Rare EpilepsyThe main purpose of this study is to investigate the long-term safety and tolerability of TAK-935/OV935 as an adjunctive therapy in patients with rare epilepsies.Phase 2RecruitingDrug: TAK-935More Info
Assessment of Potential for Chronic Liver Injury in Participants Treated With Epidiolex (Cannabidiol) Oral SolutionThis study will monitor for potential chronic liver injury and liver fibrosis, in participants treated with cannabidiol oral solution.Phase 4RecruitingDrug: CannabidiolMore Info

Top Treatments in Research

AgentClass/Mechanism of ActionDevelopment StatusCompanyClinical StudiesMore Information
TAK-935 (soticlestat)Soticlestat is a potent, highly selective, first-in-class inhibitor of the enzyme cholesterol 24-hydroxylase (CH24H), with the potential to reduce seizure susceptibility and improve seizure control. CH24H is predominantly expressed in the brain, where it converts cholesterol into 24S-hydroxycholesterol (24HC) to adjust the homeostatic balance of brain cholesterol. 24HC is a positive allosteric modulator of the NMDA receptor and modulates glutamatergic signaling associated with epilepsy.Phase 3TakedaMore InfoMore Info