Tuberous sclerosis (TS) is an inherited disorder where the brain, skin and other organs are studded with small plaques or tubers. When these occur in the brain, epilepsy commonly results. TS is one of the most common causes of genetically-inherited epilepsy, occurring in about one in every 6000 people.

TS is caused by mutations in two genes. These change a number of signalling pathways in the brain, including one controlled by a protein called mTOR, which regulates cell growth and multiplication. Investigators working at Washington University School of Medicine in St Louis, Missouri, USA, looked at whether blocking the over-working of mTOR could stop the development of some features of TS.

They investigated whether dosing with rapamycin, a drug which interacts with mTOR, could affect the development of seizures in mice with a form of TS. If left untreated, these mice normally develop seizures (which get steadily worse) between the age of one and two months, and die aged three to four months. The mice also have abnormal brain development, including over-development of some nerve cells and disorganisation of cell growth.

Dr Zeng and colleagues treated the mice with rapamycin from the age of either two weeks or 6 weeks, to find out whether starting treatment before or after the seizures started made a difference. The mice were videoed to detect seizures.

The researchers found that treatment with rapamycin before seizures started prevented seizures altogether, as long as the treatment was continued. When it stopped, the mice began to have seizures for the first time. The treatment also extended their lifespan to at least 6 months.

Mice which began treatment only after they had developed seizures continued to have them, but had fewer than untreated mice. Treated mice also lived longer than untreated mice, and also had larger brains. Analysis of brain tissue after death showed that rapamycin treatment prevented the development of the cellular abnormalities that are typical of TS.

The researchers, writing in the journal Annals of Neurology in April 2008, concluded that treatment with rapamycin not only stopped seizures, but stopped the development of the underlying features in the brain that cause them. Since rapamycin interacts with mTOR, which is present in the brains of all mammals, it's possible that this mode of treatment or a related one might be useful to treat TS in humans too.

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