Nature Medicine

Treatment during a vulnerable developmental period rescues a genetic epilepsy

Marguet SL, Le-Schulte VT, Merseburg A, Neu A, Eichler R, Jakovcevski I, Ivanov A, Hanganu-Opatz IL, Bernard C, Morellini F, Isbrandt D.

Contributed by Sloka Iyengar

Nature Medicine, vol 21 no. 12, pp 1436-1444 December 2015 doi:10.1038/nm.3987

Objective: Proper functioning of the brain is dependent on transfer of ions in and out of neurons which is mediated by ion channels situated on neuronal membranes. One such ion channel is the potassium (K+) channel called Kv7 channel. A defect in this ion channel can lead to epilepsy.

The incidence of epilepsy is high during the first few years of life as the brain is developing and is more susceptible to insults. Since there is a narrow time window where Kv7 K+ channels are formed in the brain, the authors of a recent paper investigated whether administering a drug only during that specific time window would decrease seizures. Bumetanide, a drug that has been shown to normalize ionic imbalance in neurons and reduce seizures in lab experiments, was used. The authors used mice with a mutation in Kv7 K+ channels, as previous experiments had shown that these mice develop seizures and abnormalities in structure and function during the first two weeks of life and for the rest of the adult life.

Results: Bumetanide showed no ill-effects on normal, healthy mice suggesting a possible lack of side-effects. Then, bumetanide was administered to mutant mice for the first two weeks of life; this transient treatment was enough to restore structure and function and to prevent seizure development.

Interpretation: At present, drugs for epilepsy target seizures and not epileptogenesis. This study shows administration of bumetanide before overt seizures develop can restore abnormalities in structure and function caused by deficient Kv7 K+ channels in mutant mice. A similar strategy could also be useful for individuals with hypoxia or traumatic brain injury, both of which can lead to epilepsy.

Summary for specialists