Disease Information

General Information of the Disease (ID: DIS00262)

• Name: Genetic epileptic syndromes
• ICD: ICD-11: 8A61

Type(s) of Resistant Mechanism of This Disease

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 7 drug(s) in total

Carbamazepine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Potassium inwardly rectifying channel subfamily J member 10 (KCNJ10) [1]

• Sensitive Disease: Genetic generalized epilepsies [ICD-11: 8A61.0]
• Molecule Alteration: SNP; rs12402969 C+ Genotypes CC+CT
• Sensitive Drug: Carbamazepine
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Genotyping assay
• Mechanism Description: By analyzing the association between KCNJ10 polymorphisms and anti-epileptic drug efficacy of GGEs we found the frequency of rs12402969 C allele and CC+CT genotypes were higher in GGEs drug responsive patients than that in drug resistant patients

Lamotrigine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Potassium inwardly rectifying channel subfamily J member 10 (KCNJ10) [1]

• Sensitive Disease: Genetic generalized epilepsies [ICD-11: 8A61.0]
• Molecule Alteration: SNP; rs12402969 C+ Genotypes CC+CT
• Sensitive Drug: Lamotrigine
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Genotyping assay
• Mechanism Description: By analyzing the association between KCNJ10 polymorphisms and anti-epileptic drug efficacy of GGEs we found the frequency of rs12402969 C allele and CC+CT genotypes were higher in GGEs drug responsive patients than that in drug resistant patients

Levetiracetam

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Potassium inwardly rectifying channel subfamily J member 10 (KCNJ10) [1]

• Sensitive Disease: Genetic generalized epilepsies [ICD-11: 8A61.0]
• Molecule Alteration: SNP; rs12402969 C+ Genotypes CC+CT
• Sensitive Drug: Levetiracetam
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Genotyping assay
• Mechanism Description: By analyzing the association between KCNJ10 polymorphisms and anti-epileptic drug efficacy of GGEs we found the frequency of rs12402969 C allele and CC+CT genotypes were higher in GGEs drug responsive patients than that in drug resistant patients

Oxcarbazepine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Potassium inwardly rectifying channel subfamily J member 10 (KCNJ10) [1]

• Sensitive Disease: Genetic generalized epilepsies [ICD-11: 8A61.0]
• Molecule Alteration: SNP; rs12402969 C+ Genotypes CC+CT
• Sensitive Drug: Oxcarbazepine
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Genotyping assay
• Mechanism Description: By analyzing the association between KCNJ10 polymorphisms and anti-epileptic drug efficacy of GGEs we found the frequency of rs12402969 C allele and CC+CT genotypes were higher in GGEs drug responsive patients than that in drug resistant patients

Phenobarbital

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Potassium inwardly rectifying channel subfamily J member 10 (KCNJ10) [1]

• Sensitive Disease: Genetic generalized epilepsies [ICD-11: 8A61.0]
• Molecule Alteration: SNP; rs12402969 C+ Genotypes CC+CT
• Sensitive Drug: Phenobarbital
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Genotyping assay
• Mechanism Description: By analyzing the association between KCNJ10 polymorphisms and anti-epileptic drug efficacy of GGEs we found the frequency of rs12402969 C allele and CC+CT genotypes were higher in GGEs drug responsive patients than that in drug resistant patients

Key Molecule: Potassium inwardly rectifying channel subfamily J member 10 (KCNJ10) [1]

• Sensitive Disease: Genetic generalized epilepsies [ICD-11: 8A61.0]
• Molecule Alteration: SNP; rs12402969 C+ Genotypes CC+CT
• Sensitive Drug: Phenobarbital
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Genotyping assay
• Mechanism Description: By analyzing the association between KCNJ10 polymorphisms and anti-epileptic drug efficacy of GGEs we found the frequency of rs12402969 C allele and CC+CT genotypes were higher in GGEs drug responsive patients than that in drug resistant patients

Topiramate

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Potassium inwardly rectifying channel subfamily J member 10 (KCNJ10) [1]

• Sensitive Disease: Genetic generalized epilepsies [ICD-11: 8A61.0]
• Molecule Alteration: SNP; rs12402969 C+ Genotypes CC+CT
• Sensitive Drug: Topiramate
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Genotyping assay
• Mechanism Description: By analyzing the association between KCNJ10 polymorphisms and anti-epileptic drug efficacy of GGEs we found the frequency of rs12402969 C allele and CC+CT genotypes were higher in GGEs drug responsive patients than that in drug resistant patients

Valproic acid

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Potassium inwardly rectifying channel subfamily J member 10 (KCNJ10) [1]

• Sensitive Disease: Genetic generalized epilepsies [ICD-11: 8A61.0]
• Molecule Alteration: SNP; rs12402969 C+ Genotypes CC+CT
• Sensitive Drug: Valproic acid
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Genotyping assay
• Mechanism Description: By analyzing the association between KCNJ10 polymorphisms and anti-epileptic drug efficacy of GGEs we found the frequency of rs12402969 C allele and CC+CT genotypes were higher in GGEs drug responsive patients than that in drug resistant patients

Investigative Drug(s) 1 drug(s) in total

Kainic acid

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Urothelial cancer associated 1 (UCA1) [2]

• Resistant Disease: Temporal lobe epilepsy [ICD-11: 8A61.3Y]
• Molecule Alteration: Up-regulation; Expression
• Resistant Drug: Kainic acid
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Epileptic rats model; Rattus norvegicus
• Experiment for Molecule Alteration: qRT-PCR; Immunofluorescence assay; Western bloting analysis; Overexpression assay
• Experiment for Drug Resistance: Morris water maze analysis
• Mechanism Description: LncRNA-UCA1 inhibits the astrocyte activation in the temporal lobe epilepsy via regulating the JAK/STAT signaling pathway.

References

• Ref 1: Common variants of KCNJ10 are associated with susceptibility and anti-epileptic drug resistance in Chinese genetic generalized epilepsies .PLoS One. 2015 Apr 13;10(4):e0124896. doi: 10.1371/journal.pone.0124896. eCollection 2015. 10.1371/journal.pone.0124896
• Ref 2: LncRNA-UCA1 inhibits the astrocyte activation in the temporal lobe epilepsy via regulating the JAK/STAT signaling pathwayJ Cell Biochem. 2020 Oct;121(10):4261-4270. doi: 10.1002/jcb.29634. Epub 2020 Jan 7.