Myoclonic Epilepsy of Lafora (EPM2)
Myoclonic epilepsy of Lafora (EPM2) is a rare, adult-onset, autosomal recessive disorder. With our pioneering efforts in EPM2 research, we are at the forefront of developing cutting-edge diagnostic tools and therapeutics to facilitate the effective management of EPM2. As your reliable partner in EPM2 research, we offer unmatched support to fulfill your scientific research needs.
Introduction to EPM2
Myoclonic epilepsy of Lafora (EPM2), also known as Lafora disease, is a rare and devastating genetic disorder that primarily affects children and adolescents. EPM2 is a devastating neurological disorder characterized by the gradual onset and progression of myoclonus epilepsy, resulting in severe neurological symptoms and a reduced lifespan. The incidence of EPM2 is approximately four cases per one million persons.
Fig. 1 The mechanisms of EPM2. (Worby, Carolyn A., et al., 2008)Pathogenesis of EPM2
In EPM2, a distinguishing feature is the presence of intracellular aggregates known as Lafora bodies. These Lafora bodies are composed of abnormal glycogen molecules or polyglucosans, which have an irregular shape and accumulate within the cytoplasm.
Mutations in the EPM2A or EPM2B gene disrupt glycogen metabolism and impair the functions of laforin and malin proteins, leading to malformation and accumulation of glycogen. Abnormal glycogen accumulation in the form of Lafora bodies interferes with cellular processes and leads to neurodegeneration.
Diagnostics Development of EPM2
Significant progress has been made in the diagnostics development of EPM2. Currently, the main diagnostic methods include symptom evaluation, genetic testing, and imaging examinations.
Symptom Evaluation
Physicians arrive at an initial diagnosis by assessing an individual's symptoms, reviewing their medical history, and considering any relevant family history.
Genetic Testing
Gene sequencing and other advanced technologies are utilized to detect mutations in the EPM2A or EPM2B gene, enabling precise diagnosis of the disease.
Imaging Examinations
EEG and MRI can be used to evaluate abnormalities in brain waves and brain structure, helping to distinguish diseases with similar symptoms to EPM2.
Therapeutics Development of EPM2
- Targets of EPM2 Therapy Development
| Target | Description |
|---|---|
| Glycogen Metabolism Recovery Pathway | EPM2 is characterized by abnormalities in glycogen metabolism, leading to the accumulation of Lafora bodies. Modulating enzymes involved in glycogen synthesis and degradation or targeting pathways that regulate glycogen metabolism can help prevent or reduce Lafora body formation. For example, phosphatase activators facilitate the degradation of abnormal glycogen and inhibit the formation of inclusion bodies. |
| Neuroinflammation and Oxidative Stress Inhibitory Pathways | Studies have shown that EPM2 is associated with increased levels of inflammatory markers and oxidative damage in the brain. Anti-inflammatory drugs and antioxidants can inhibit neuroinflammation and oxidative stress in EPM2 to reduce neuronal damage and improve overall neurological function. |
- Types of EPM2 Therapy Development
Gene Therapy
Gene therapy aims to restore normal function of the laforin and malin proteins by delivering functional copies of the EPM2A or EPM2B genes to affected cells. This can be achieved through the use of viral vectors or genome editing technology to introduce corrected genes.
Our Services
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 EPM2.
Recognizing the significance of animal disease models in the therapy development for EPM2, we offer our expertise in establishing animal models specifically tailored for EPM2. These models serve as invaluable tools to facilitate the safety evaluation and pharmacokinetics study of your drug candidates.
Animal Models of EPM2
| Genetically Engineered Models | |||
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| Our company is a leader in the development of genetically engineered models for EPM2 research. Leveraging our expertise in genetic engineering technologies, specifically CRISPR/Cas9 technology, we created a highly accurate and reliable model that faithfully replicates the genetic alterations found in human EPM2. | |||
| Optional Models |
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| Optional Species | Mice, Canines, Rats, Zebrafish, 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
- Jansen, Anna C., and Eva Andermann. "Progressive myoclonus epilepsy, Lafora type." (2019).
- Worby, Carolyn A., Matthew S. Gentry, and Jack E. Dixon. "Malin decreases glycogen accumulation by promoting the degradation of protein targeting to glycogen (PTG)." Journal of Biological Chemistry 283.7 (2008): 4069-4076.
- Burgos, Daniel F., et al. "Epm2aR240X knock-in mice present earlier cognitive decline and more epileptic activity than Epm2a−/− mice." Neurobiology of disease 181 (2023): 106119.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.