Activity of drugs and components of natural origin in the severe myoclonic epilepsy of infancy (Dravet syndrome).
The sea anemones (Cnidaria) produce neurotoxins, polypeptides active on voltage-gated sodium channels, which induce a non-inactivating condition, with consequent seizures and paralysis in zebrafish (Danio rerio). In humans, severe myoclonic epilepsy of infancy (SMEI) is due to SCN1A gene mutation, which causes a non-inactivating sodium channels condition with seizures. Some symptoms, such as age of first seizure, repetitive events, frequent status epilepticus, scarce responsiveness to antiepileptic drugs (AEDs), may be due to superimposed environmental causes. The authors report a case of SMEI treated for years with benzodiazepines and subsequently with valproate. The attenuation of the frequency of epileptic events and of time in seizing, but no change in burst duration and EEG events was observed. These results are similar to those reported in the literature about zebrafish scn1Lab mutant, which recapitulates the SCN1A symptoms and AED resistance occurring in humans. During seizures the production of polypeptides similar to sea anemones neurotoxins, causing repetitive seizures, status epilepticus, and AED resistance can be hypothesized in subjects with SCN1A mutation.
Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DINOGMI), University of Genova, Largo Gaslini 5, Genova, Italy. agostinoberio@ospedale-gaslini.ge.it.
Agostino
A
Berio
Attilia
A
Piazzi
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D003063:Cnidaria / Q000737:chemistry; D003064:Cnidarian Venoms / Q000145:classification / Q000494:pharmacology*; D004195:Disease Models, Animal; D004351:Drug Resistance; D004569:Electroencephalography; D004831:Epilepsies, Myoclonic / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D051379:Mice; D008818:Mice, Neurologic Mutants; D018716:Molecular Mimicry; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D012615:Sea Anemones / Q000737:chemistry; D061585:Voltage-Gated Sodium Channel Agonists / Q000633:toxicity*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000187:drug effects / Q000235:genetics
D000927:Anticonvulsants; D003064:Cnidarian Venoms; D062550:NAV1.1 Voltage-Gated Sodium Channel; D010455:Peptides; C568242:SCN1A protein, human; D061585:Voltage-Gated Sodium Channel Agonists; D029961:Zebrafish Proteins; C000605300:scn1laa protein, zebrafish