Emerging treatments in the management of tuberous sclerosis complex

Tuberous sclerosis complex is a genetic disorder characterized by the formation of nonmalignant hamartomas in the brain, heart, skin, kidney, lung, and other organs. It is associated with autism, epilepsy, and other neurocognitive and behavioral disabilities. Wide phenotypic variation occurs in disease severity and natural course: some patients demonstrate minimal effects, e.g., skin changes; others manifest profound seizures and mental retardation. Tuberous sclerosis complex is caused by mutations in either the tuberous sclerosis complex 1 or 2 gene (coding for hamartin and tuberin, respectively). The tuberous sclerosis complex 1/tuberous sclerosis complex 2 protein dimer complex is a crucial inhibitory element in the mammalian target of rapamycin pathway, regulating cell growth and proliferation. Until recently, few options existed, other than surgery, for treating symptoms of tuberous sclerosis complex related to the growth of hamartomas. Increased understanding of the genetic cause of the disease and underlying dysregulation of the mammalian target of rapamycin pathway has led to clinical trials of mammalian target of rapamycin inhibitors, including sirolimus and everolimus. This review gives an overview of tuberous sclerosis complex and its molecular causes, and summarizes results from recent clinical trials of mammalian target of rapamycin inhibitors in patients with the disease.