Table 1.
Animal models of genetic mTOR hyperactivation and seizures and the response to treatment with an mTOR inhibitor.
| Model | Deletion timing | Treatment timing | Treatment response | Ref |
|---|---|---|---|---|
| Tsc1 induced KO | 2–4 months postnatal | Rapamycin after seizure onset | Prolonged survival; no seizures during treatment | [49] |
| Tsc1 induced KO | 2–4 months postnatal | Rapamycin immediately after deletion | No seizures developed during treatment | [49] |
| Tsc1 Syn-neuronal KO | Embryonic | Rapamycin treatment started at P7–P9 | Prolonged survival, weight gain, absence of seizures during treatment | [38] |
| Tsc1 GFAP KO | Embryonic | Rapamycin treatment started at P14 | No seizures developed; prolonged survival during treatment | [37] |
| Tsc1 GFAP KO | Embryonic | Rapamycin treatment as juvenile (6 week) | No seizures developed; prolonged survival during treatment | [37] |
| Tsc1 nestin KO | Embryonic | Rapamycin treatment started at P8 | No seizures developed; prolonged survival during treatment | [39] |
| Tsc1 Emx1 KO | Embryonic | Rapamycin treatment started at P13–15 | No mortality or seizures during treatment | [41] |
| Tsc2 GFAP KO | Embryonic | Rapamycin treatment started at P14 | Fewer seizures | [40] |
| Tsc2 GFAP KO | Embryonic | Rapamycin E12.5 to birth (pre) | Seizures improved | [42] |
| Tsc2 GFAP KO | Embryonic | Rapamycin birth to P21 (post) | No seizures developed; prolonged survival during treatment | [42] |
| Tsc2 GFAP KO | Embryonic | Rapamycin E12.5 to P21 (combined) | No seizures developed; prolonged survival during treatment | [42] |
| Pten GFAP KO | Embryonic | Temsirolimus in adult mice; post-symptoms | Decreased seizures and mortality | [82] |
| Pten GFAP KO | Embryonic | Rapamycin in adolescent mice; post-symptoms | Decreased seizures; persisted following discontinuation of treatment | [67] |
| Pten GFAP KO | Embryonic | Rapamycin in adolescent mice; post-symptom; subset received several more doses | Decreased seizures and improved survival; recurrence at 10 weeks; seizures decreasing with intermittent treatment | [83] |
| Pten NSE KO | Embryonic | Rapamycin in adult mice following development of seizures | Decreased seizure duration and frequency | [84] |
| Pten induced KO | P14 | Rapamycin 2–5 days post tamoxifen injection | Decreased seizures | [44] |
| Wag/Rij KO | Embryonic | Rapamycin in adult rats | Rapamycin decreased seizures within 30 minutes of administration. Treatment prior to development of epilepsy decreased absence seizures | [64] |
| STRADA KO | Embryonic | Rapamycin E15–E19 (Dams) | Did not measure seizures; histopathological findings improved | [47] |
Abbreviations: E embryonic day, GFAP glial fibrillary acidic protein, KO knockout, P postnatal day, PTEN phosphatase and tensin homolog on chromosome 10, STRADα STE20-related kinase adapter alpha, Tsc1 tuberous sclerosis complex 1 protein, Tsc2 tuberous sclerosis complex 2 protein, Wag/Rij Wistar Albino Glaxo rat from Rijswijk.