Progressive Myoclonic Epilepsy (PME)
The combination of neurodegeneration, genetic diversity, and resistance to standard antiepileptic drugs makes progressive myoclonus epilepsy (PME) especially difficult to treat. Through understanding PME's genetic and pathobiological features, Protheragen is developing precision animal models and targeted therapies, thereby advancing preclinical drug development. We aim to provide comprehensive support to simplify your therapeutic development process.
Overview of Progressive Myoclonic Epilepsy (PME)
Progressive myoclonic epilepsy (PME) is a diverse and uncommon genetic disorder of the nervous system with myoclonus (abrupt muscle twitching), epilepsy that escalates, and neurodegeneration as defining features. These are usually resistant to treatment with antiepileptic drugs (AEDs), leading to significant disability and early death. PME syndromes start in childhood or teenage years and involve a worsening course of ataxia, dementia, and motor dysfunction.
| Disease | Genetic Cause | Pathological Hallmark | Key Clinical Features | Disease Progression |
| Lafora Disease | EPM2A or NHLRC1 mutations | Polyglucosan inclusions (Lafora bodies) | Severe myoclonus, occipital seizures, dementia | Rapid progression (death in ~10 years) |
| Unverricht-Lundborg Disease (ULD) | CSTB mutation | Loss of cystatin B protease inhibitor | Action myoclonus, tonic-clonic seizures | Slower progression than Lafora |
| Neuronal Ceroid Lipofuscinoses (NCLs) | CLN gene family mutations | Lipopigment accumulation in lysosomes | Visual loss, cognitive decline, seizures | Variable (infantile to adult forms) |
| Myoclonic Epilepsy with Ragged Red Fibers (MERRF) | MT-TK mitochondrial mutation | Abnormal mitochondria in muscle fibers | Myoclonus, myopathy, hearing loss | Progressive multisystem decline |
Pathogenesis of Progressive Myoclonic Epilepsy (PME)
Progressive myoclonic epilepsy (PME) results from genetic mutations that causes nerve cell deterioration via different but interrelated pathological processes. Hyperexcitability of neuronal cells results from insufficient inhibitory neurotransmission, as exemplified by Unverricht-Lundborg disease, a condition characterized by excessive synaptic excitation in patients with CSTB deficiency. Also, abnormal protein aggregates such as Lafora bodies in EPM2A/NHLRC1 mutations and lipopigments in CLN disorders compromise homeostasis while MERRF syndrome among others, which have mitochondrial dysfunctions, weaken energy metabolism.
Fig.1 Mouse model of progressive myoclonic epilepsy (PME). (Feng H, et al., 2024)
Therapeutic Development for Progressive Myoclonic Epilepsy (PME)
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
| Ropinirole Hydrochloride | Dopamine D2/D3 receptor agonist; modulates basal ganglia output to reduce myoclonus | Dopamine receptors | NCT00639119 | Phase II |
| Brivaracetam | SV2A synaptic vesicle protein modulator; enhances inhibitory neurotransmission | Synaptic vesicle glycoprotein 2A (SV2A) | NCT00368251 | Phase III |
| Intravenous Immunoglobulin (IVIG) | Immunomodulation; neutralizes autoantibodies and suppresses neuroinflammation | Fcγ receptors, complement system, cytokines | NCT03351569 | Phase II |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
To improve the diagnosis and treatment of progressive myoclonic epilepsy (PME), Protheragen provides comprehensive services in the areas of diagnostic and therapeutic development. Addressing the different molecular causal factors of PME motivates us to address the critically lacking medical treatment solutions and devise novel precision medicine targeted therapies. Protheragen's team of specialists has unique skills to develop highly relevant models of disease which allow for the thorough assessment of the safety, efficacy, and mechanism of action of potential therapeutics.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
- Cystatin B-deficient Mouse Models: Genetically engineered mice lacking the CSTB gene, replicating Unverricht-Lundborg disease (ULD) pathology.
- NCL Mouse Models: Transgenic mice carrying CLN gene mutations that mimic neuronal ceroid lipofuscinoses (NCLs).
At Protheragen, we are committed to validating and optimizing therapies for progressive myoclonic epilepsy (PME) through comprehensive pharmacodynamics (PD), pharmacokinetics (PK) and toxicology research services to ensure their successful regulatory approval. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Feng H, Clatot J, Kaneko K, et al. Targeted therapy improves cellular dysfunction, ataxia, and seizure susceptibility in a model of a progressive myoclonus epilepsy[J]. Cell Reports Medicine, 2024, 5(2).