In our April 2008 newsletter, we discussed how a drug called rapamycin, commonly prescribed to prevent organ transplant rejection, was shown to suppress seizures associated with tuberous sclerosis (TS, a condition associated with brain abnormalities similar to cortical dysplasia). Rapamycin inhibits a protein called mTor, which helps to regulate cell growth, cell proliferation, cell movement, cell survival and protein synthesis. Failure in the regulation of mTor regulation appears to play a vital role in TS.

Now, a year later, human trials using rapamycin in TS are being conducted in the US; a very promising progression. We are still awaiting the results of these.

Cortical dysplasia (CD) is the most common cause of epilepsy in children, and a high proportion of these cases are refractory to drug therapy. Although surgery is being increasingly used to treat drug-resistance in CD, there is still a lot of uncertainty in terms of outcome. Researchers are therefore keen to find new types of medication that might succeed where conventional anti-epileptic drugs (AEDs) have failed.

This has been a difficult task, however, because it requires an animal model that displays all of the features of CD, and until now, this has not existed.

Investigators at Rutgers, the State University of New Jersey, have successfully remedied this situation. They bred mice that lacked a gene called Pten, which blocks cell growth in some neurons, causing them to display all the characteristic traits of CD: enlarged cortical neurons and abnormal EEG activity with spontaneous seizures. There was also increased mTor activity in these models.

When they administered rapamycin, the team found that the severity and duration of seizures was strongly suppressed. Dr D'Arcangelo, the project leader commented, "We demonstrated that rapamycin is a novel and effective anti-epileptic agent that suppresses seizures in our mice as well as in the TS model, and this has raised some hope for the future."

The group hopes that these results will lead to human trials of rapamycin for CD, in the same way as it has for TS. If these show the same promise, rapamycin could be developed as a possible treatment for patients with epilepsy associated with CD and similar disorders.

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