Same mTOR pathway also involved in autism, Alzheimer’s, Parkinson’s

An important Phase III clinical trial confirms that the anti-rejection drug everolimus can dramatically reduce brain tumor growth in patients with tuberous sclerosis complex (TSC).

The study -- published online Nov. 14, 2012, in The Lancet -- was led by David Franz, MD, director of the TSC Clinic at Cincinnati Children’s.   

“Every patient in this study experienced a decrease in size of their tumors, and no patient required surgery for their tumors after treatment with everolimus,” Franz says. “Thirty-five percent of patients in this study on everolimus had at least a 50 percent reduction in tumor volume after an average of 42 weeks on medication.”

Until recently, surgery was the standard therapy for treating subependymal giant astrocytomas (SEGAs), but everolimus offers a new alternative, Franz says.

Similar results from a smaller Phase II study of everolimus were published in 2010 in The New England Journal of Medicine. Based on that data, the U.S. Food and Drug Administration (FDA) granted accelerated approval of everolimus for patients with SEGAs.  The FDA had already approved using the drug to treat TSC-related kidney tumors, based on studies by John Bissler, MD, a nephrologist at Cincinnati Children’s.

About 1 million people worldwide live with TSC, including nearly 50,000 in the US. The TSC Clinic at Cincinnati Children's, which follows more than 800 children and adults, is believed to be the largest in the world.

Everolimus also may have benefits beyond treating TSC. The same mTOR signaling pathway associated with overactive cell growth in TSC also is implicated in Alzheimer’s disease, type 2 diabetes, Parkinson’s disease, Huntington’s disease and autism. This makes everolimus, an mTOR inhibitor, a potential candidate to treat these disorders, Franz says.

Everolimus is marketed by Novartis, which provided drug and financial support for the study. In addition, several of the Phase III study co-authors are employees of Novartis.