1. Field of the Invention
The present invention relates to a composition for the prevention and treatment of absence seizure comprising PKC agonist as an active ingredient.
2. Description of the Related Art
Epilepsy is a seizure disease whose beginning symptom is loss of consciousness with tonic convulsion cramp followed by clonic convulsion. The cause of this disease is presumably mesial temporal sclerosis, brain tumor, trauma, stroke, congenital disorder, and brain infection, which is believed not inherited.
Epilepsy is largely divided into two categories, which are generalized seizure and partial seizure. Generalized seizure is characterized by the simultaneous overall seizure in the total area of cerebrum. Clinically, generalized seizure begins simultaneously in the right and the left side of the body which accompanies loss of consciousness. So, when electroencephalography is performed, epilepti form discharge is observed overall in both sides of cerebrum. Generalized seizure includes the following sub-types: tonic clonic seizure, petit mal seizure, myoclonic seizure, and atonic seizure. Tonic clonic seizure is also called as grand mal seizure and is the most frequent type of seizure. When tonic clonic seizure begins, a subject loses his consciousness abruptly without any warning sign, followed by convulsions in muscles over the whole body. Seizure progresses from the early tonic phase, which is the stage of body stiffness, to the late clonic phase, that is the stage of shaking body. Petit mal seizure is mainly observed among children at the age group of 5-7 years old, which allegedly disappears after puberty. It accompanies unconsciousness for several seconds, blinking, and light muscle cramp. Myoclonic seizure is the temporary acute muscular contraction in the whole body without losing consciousness as if a sudden shock. Atonic seizure is characterized by sudden body weakness with shock, unlike spasm.
Partial seizure shows warning signs when it beings. Partial seizure is divided into complex partial seizure and simple partial seizure according to the clouding of consciousness. However, in the early stage of partial seizure, epilepti form discharge is apt to be dispersed to both sides of the brain, so that it progresses into generalized seizure. Complex partial seizure takes ⅔ of the total seizures, whose symptoms vary with patients. The light complex partial seizure looks like petit mal seizure, while the severe complex partial seizure shows similar symptoms to grand mal seizure. So, it is most difficult to be diagnosed. After the warning signs such as auditory hallucination, olfactory hallucination and visual hallucination, automatism which is characterized by repeated hands, feet, and mouth movement, and other behavioral symptoms such as turning the body one side or yelling, or leaning power on one arm and one leg can be observed, but the patient cannot recognize his own symptoms. Simple partial seizure happens locally in a part of the brain particularly in the part responsible for a specific function. It is generally known that such simple partial seizure occurs in the motor cortex or sensory cortex of the brain.
Absence seizure is a kind of epilepsy that does not carry seizure. It only shows unconsciousness for a moment and SWD (spike-and-wave discharge). In thalamocortical (TC) neurons, low voltage dependent burst firing is accompanied. This seizure shows two different sub-types: one is observed in infancy at the age of around 6 and the other is observed in adolescence at the age of around 12. The frequency of this seizure is higher in women. It can be triggered by hyperventilation and photic stimulation. Absence seizure takes 10% of total seizures outbreaking in children. However, the mechanism of absence seizure is still not disclosed. Accordingly, the treatment method has not been established.
The object of the treatment for absence seizure is to reduce frequency of seizure eventually to prevent injury during unconsciousness including seizure or to improve memory loss or other troubles in daily life resulted from the seizure and to reduce side effects that could be more serious than the seizure itself.
For the treatment of epilepsy, drugs for oral administration such as Phenytoin, Carbamazepine, Valproic acid, Phenobarbital, ethosuximide, Clonazepam, clobazam and Primidone have been used. Recently, the treatment of epilepsy becomes more advanced owing to the newly developed drugs like vigabatrin, Zonisamide, Lamotrigine, topiramate, Oxcarbazepine and Gabapentine, etc. However, the results of the treatment of epilepsy using the said medicines are not satisfactory. The chances of controlling epilepsy with a single medicine are 60-70% and 20-25% requires co-administration of different medicines. The last 10% does not show any improvement with any of the said medicines.
Make matter worse, the said drugs carry side effects. For example, Clonazepam can bring the medicinal effect shortly after the administration but resistance to this drug and other side effects are observed frequently. It was also reported that Clonazepam could cause damage in the liver. So, Clonazepam is not recommended. Even though the said drugs are effective in the treatment of absence seizure, the known side effects are serious and prescription has to be different over the cause of the seizure. Thus, the administration of those drugs has to be done after doctor's diagnosis.
Therefore, the present inventors tried to develop a novel therapeutic agent for absence seizure, and finally completed this invention by confirming that SWD, the characteristic of absence seizure, was reduced when PKC agonist was administered to the phospholipase C beta4 (PLCβ4) knock-out mouse.