Lennox-Gastaut Syndrome (LGS)
Lennox-Gastaut syndrome (LGS) is a severe epilepsy disorder that usually begins in infancy or early childhood. Our company is dedicated to advancing the diagnosis and therapeutics of LGS. Our team of researchers and scientists utilize cutting-edge technology to develop innovative diagnostic tools and therapeutic drugs, aiming to accelerate scientific progress in this field. As your trusted partner, we offer comprehensive and high-quality services tailored to meet your unique scientific research needs.
Introduction to LGS
Lennox-Gastaut syndrome (LGS) is a complex and severe childhood-onset epilepsy disorder characterized by multiple types of seizures, cognitive dysfunction, developmental delays, and electroencephalogram (EEG) abnormalities. LGS usually emerges in children between 3 and 5 years old and often persists into adulthood. LGS is relatively rare, with an incidence of approximately 0.1 to 0.28 per 100,000 people per year.
Fig. 1 Therapy algorithm for individuals with LGS. (Cross J H, et al., 2017)Pathogenesis of LGS
The exact pathogenesis of LGS is not fully understood, but several factors and mechanisms are believed to contribute to its development.
Brain Structural Abnormalities
Some cases of LGS are associated with structural brain abnormalities, such as cortical malformations, cortical dysplasia, or brain lesions resulting from brain injury, infection, or genetic mutations. These structural abnormalities can disrupt normal brain function and contribute to the development of LGS.
Genetic Factors
Genetic mutations and alterations are thought to play a role in LGS. Mutations in genes such as SCN1A, SCN2A, STXBP1, and others have been identified in a subset of LGS cases, suggesting a genetic component to the disorder. Identifying genetic mutations associated with LGS helps to understand the underlying disease mechanisms.
Neurotransmitter Imbalances
LGS is associated with imbalances in various neurotransmitters in the brain. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter, while glutamate is an excitatory neurotransmitter. Dysregulation of the balance between these neurotransmitters can lead to increased neuronal excitability and the occurrence of seizures.
Diagnostics Development of LGS
The development of diagnostics for LGS aims to improve the early and accurate identification of the syndrome, enabling timely intervention and appropriate management. Below are common diagnostic methods for LGS.
- Medical Evaluation is the first step in diagnosing LGS. The approach primarily takes into account characteristics of the disease, including multiple epilepsy types, cognitive impairment, and specific EEG patterns.
- Physical Examination mainly includes MRI and electroencephalography (EEG). These tests can assess brain structure and activity features that help support the diagnosis of LGS.
- Genetic Testing may be performed to identify specific genetic mutations associated with LGS. Mutations in genes such as SCN1A, SCN2A, STXBP1, and others have been found in a subset of LGS cases. Genetic testing can help confirm the diagnosis and provide insights into the underlying genetic causes.
Therapeutics Development of LGS
- Therapeutic Drugs of LGS
The therapeutics for LGS aim to improve seizure control, manage associated symptoms, and enhance the overall quality of life for individuals with the condition. At present, LGS therapeutic drugs are mainly used to control seizures, related drugs are as follows:
- Valproate
- Lamotrigine
- Topiramate
- Clobazam
- Rufinamide
- Felbamate
- Therapy Progress of LGS
Alongside medications, various other approaches are being developed to manage symptoms of LGS. These include surgical interventions, dietary modifications, gene therapy, etc.
Our Services
Surgical Interventions
Studies have shown that LGS individuals who undergo radical surgery show very good prognosis, with 80% of sufferers under 5 years old and 40% of sufferers over 5 years old becoming seizure-free. Common surgical methods include vagus nerve stimulation, corpus callosotomy, and transcranial direct current stimulation.
Dietary Modifications
The ketogenic diet is a high-fat, low-carbohydrate, and adequate-protein diet. Studies have shown that nearly half of children with LGS experienced a 50% reduction in seizures after 1 year on a ketogenic diet. This demonstrates the effectiveness of the ketogenic diet in reducing seizures in LGS.
Gene Therapy
Gene therapy involves delivering genetic material to target cells to restore normal gene function or suppress the effects of the mutated gene. Preclinical and early-phase clinical trials are being conducted to explore the potential of gene therapy in LGS.
Our company has established a comprehensive platform for developing rare disease diagnostics and therapies, encompassing small molecule drug, cell therapy, gene therapy, therapeutic antibody, therapeutic peptide, and therapeutic protein. Through our dedicated platforms, we are fully devoted to advancing the development of innovative diagnostic tools and therapies for LGS.
Animal models serve as valuable tools for studying neurological disorders like LGS. We offer our expertise in establishing animal models specifically tailored for LGS. These models serve as invaluable tools to facilitate the safety evaluation and pharmacokinetics study of your drug candidates.
Animal Models of LGS
| Genetically Engineered Models | |||
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| Our company specialize in developing genetically engineered models for LGS research. Our expertise in genetic engineering techniques, such as CRISPR/Cas9 technology, allows us to generate accurate and reliable models, allowing researchers to study disease mechanisms and potential therapeutic targets with greater confidence. | |||
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| Optional Species | Mice, Zebrafish, Non-human Primates, Others | ||
If you are interested in our services, please don't hesitate to contact us for more information and a detailed quotation regarding the specific services you require.
References
- Cross J H, Auvin S, Falip M, et al. Expert opinion on the management of Lennox–Gastaut syndrome: treatment algorithms and practical considerations[J]. Frontiers in neurology, 2017, 8: 285292.
- Qu S, Catron M, Zhou C, et al. GABAA receptor β3 subunit mutation D120N causes Lennox–Gastaut syndrome in knock-in mice[J]. Brain communications, 2020, 2(1): fcaa028.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.