Everolimus for the treatment of refractory seizures associated with tuberous sclerosis complex (TSC): current perspectives
| Autor: | André B. Rietman, Iris E. Overwater, Marie Claire Y. de Wit, Agnies M van Eeghen |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Oncology
Drug Refractory seizures congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty media_common.quotation_subject 030204 cardiovascular system & hematology Epileptogenesis 03 medical and health sciences Tuberous sclerosis Epilepsy 0302 clinical medicine Internal medicine medicine Pharmacology (medical) 030212 general & internal medicine General Pharmacology Toxicology and Pharmaceutics PI3K/AKT/mTOR pathway Loss function media_common Chemical Health and Safety Everolimus business.industry General Medicine medicine.disease business Safety Research medicine.drug |
| Zdroj: | Therapeutics and Clinical Risk Management. 15:951-955 |
| ISSN: | 1178-203X |
| Popis: | Up to 90% of patients with tuberous sclerosis complex (TSC) have epilepsy, and in over half of patients seizure control cannot be achieved by regular antiepileptic drugs. The underlying problem is mTOR hyperactivation due to loss of function of the TSC proteins. Treatment with everolimus, an mTOR inhibitor, has been shown to be of great benefit to TSC patients, both in reducing tumor growth and as a treatment for intractable epilepsy. Up to 40% of TSC patients with intractable epilepsy show a clinically relevant seizure response to everolimus. It has not yet fully lived up to its promise as a disease-modifying drug, however, as half of TSC patients with intractable epilepsy do not show a clinically relevant seizure frequency reduction. There is no evidence yet of a positive effect on the cognitive and neuropsychiatric deficits in TSC patients. In preclinical studies, mTOR inhibition can rescue abnormal neuronal migration and synapse formation that is caused by mTOR hyperactivation. These studies show a critical time window that suggests that mTOR inhibition may be most beneficial in young children. The trials done so far have not studied treatment in children under 2 years of age, although case series suggest that the safety profile is similar to that in older children. Further studies into the optimal time window, dosing schedules and possibly combination with other drugs may further improve the benefit of everolimus for TSC patients. |
| Databáze: | OpenAIRE |
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