Thursday, June 10, 2010
86th Annual AANP Meeting: Rapamycin as a possible treatment for tuberous sclerosis
Dr. Elizabeth Henske (pictured), an oncologist, talked about the spectrum of clinical manifestations seen in tuberous sclerosis complex (TSC) and experiemental therapeutics based on understanding the molecular underpinnings of the syndrome. Given that the genes mutated in tuberous sclerosis (TSC1 and TSC2) inhibit mTOR, Henske said that researchers are looking into the use of rapamycin, an inhibitor of mTOR, as a treatment for not only the more obvious manifestations of TSC, such as subependymal giant cell astrocytoma, but even for reversing learning deficits in children with TSC. In a mouse model of TSC in which there is no pathological evidence of brain lesions, it was discovered that these mice have cognitive defects as evidenced by water-maze testing. "And the thing that just gives me shivers to think about," says Henske, "is that these cognitive deficits are correctable with rapamycin. Five days of rapamycin! So that has caused a big shift in the thinking about children with tuberous sclerosis who have cognitive defects and many parents are actually putting their children on rapamycin off-trial, but we would really like to do a cognitive trial and figure out whether there is benefit in children with tuberous sclerosis who are taking rapamycin. The parents, many of them, have very compelling anecdotal studies of improvement in their childrens' learning or behavior." Therefore, Dr. Henske will be working on an efficacy and safety trial, with funding from the Tuberous Sclerosis Alliance, to see if rapamycin can improve cognitive function in these children. "If there is benefit with rapamycin neurocognitively, it would just be wonderful."