http://rdf.ncbi.nlm.nih.gov/pubchem/patent/WO-2022219021-A1
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_e3b4f2ef8f062dcde3a2b7cd81748472 http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_43a72884e25aaecffebe0942132d704f http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_96c84c8efcc6aeaf350488384f4952ff |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P25-08 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K45-06 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-501 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-5415 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K31-501 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K31-5415 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K45-06 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61P25-08 |
| filingDate | 2022-04-13-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| inventor | http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_47f58fdb3c142f80dd27eadf1cb41371 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_cea4a14ba9812a11bc34b37dfdd76037 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_c19ac1223a2faed4825db529af418421 |
| publicationDate | 2022-10-20-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | WO-2022219021-A1 |
| titleOfInvention | Methods and pharmaceutical compositions for treating refractory epilepsy |
| abstract | Cation chloride cotransporters (CCC) play a critical role in neuronal chloride homeostasis. Altered CCC expression and function has emerged as a hallmark of wide range of psychiatric and neurological conditions, including various forms of epilepsy. Elevated intraneuronal chloride concentration is thought to result in depolarizing GABA signaling that may contribute to pathological activities and seizures. Compensating for the dysregulation of CCC function in the pathology therefore appears as a promising therapeutic strategy. Bumetanide, an antagonist of the Na/K/Cl co-transporter NKCC1 failed to prevent acute neonatal seizures in the NEMO trial. Here, instead, the inventors tested the effects of novel candidate KCC2 enhancers on epileptiform activity in vitro and in vivo. The inventors show that FDA-approved prochlorperazine (PCPZ) as well as CLP257 potentiate KCC2 function by promoting its membrane clustering, through a mechanism/pathway that does not involve phosphorylation of canonical residues. Both PCPZ and CLP257 reduce interictal activity recorded in vitro in epileptogenic postoperative brain samples from mesial temporal lobe epilepsy patients. In addition, chronic PCPZ administration strongly reduces seizure occurrence in a mouse model of temporal lobe epilepsy. Their results demonstrate for the first time the antiepileptic potential of a KCC2 enhancer and suggest PCPZ may be used in adjunctive therapy in pharmaco-resistant epilepsy. |
| isCitedBy | http://rdf.ncbi.nlm.nih.gov/pubchem/patent/CN-116076440-A http://rdf.ncbi.nlm.nih.gov/pubchem/patent/CN-116076440-B |
| priorityDate | 2021-04-14-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
Incoming Links
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