Blockade of a cystine/glutamate transporter can reduce glioma-induced epilepsy in mice, reports research published online this week in Nature Medicine.
Patients with brain cancers called gliomas often have seizures due to secretion of the excitatory neurotransmitter glutamate from the tumor cells. Gliomas require the amino acid cystine to survive, and the cystine/glutamate transporter on tumor cells shuttles cystine into the tumor cell while simultaneously secreting large amounts of glutamate onto the surrounding brain tissue. This causes neurons in the tumor vicinity to become overexcitable, resulting in the development of seizures.
Harald Sontheimer and colleagues administer a Food and Drug Administration approved inhibitor of the cystine/glutamate transporter called sulfasalazine, which is currently used to treat patients with gut inflammation, to tumor-bearing mice. They show that the drug can prevent the increase in brain glutamate levels caused by the tumors, and can reduce glioma-induced epilepsy in mice. The findings therefore suggest a potential new therapeutic approach to reducing brain tumor-induced seizures in humans.