DEPDC5, meet the mTOR pathway – a novel mechanism in genetic focal epilepsies

Variable foci. A few weeks ago, we discussed the recent gene finding in Familial Partial Epilepsy with Variable Foci, a rare but puzzling familial epilepsy syndrome. DEPDC5 was identified as the culprit gene. However, the potential function of the gene product left researcher scratching their heads. Now, a recent paper in Science suggests that DEPDC5 might interact with the mTOR pathway, the master regulator of growth. Should we reconsider the role of the mTOR pathway in genetic focal epilepsies? Continue reading

STRADA mutations, mTOR activation and personalized medicine using rapamycin

Rapamycin. The mTOR pathway, known through its role in Tuberous Sclerosis Complex (TSC), becomes increasingly important in epilepsy. A wide range of epilepsies caused by brain malformations are due to mutations in genes involved in this pathway, and several neurodevelopmental disorders associated with macrocephaly, intellectual disability and epilepsy are known, where components of this pathway are altered due to germline mutations. For one of these disorders named PMSE (polyhydramnios, megalencephaly and symptomatic epilepsy), a recent paper in Science Translational Medicine reports the effects of treatment with rapamycin, an mTOR inhibitor. The results demonstrate that personalized medicine might in part be promising, asexisting drugs can be used in rare genetic diseases. Continue reading