Tuberous sclerosis complex (
TSC) is a multisystem disease associated with an overall reduction in life expectancy due to the possible occurrence of different life-threatening conditions. Subjects affected by
TSC are, in fact, at risk of
hydrocephalus secondary to the growth of subependymal giant cell
astrocytomas, or of
sudden unexpected death in epilepsy. Other nonneurological life-threatening conditions include abdominal
bleeding owing to renal
angiomyolipomas rupture,
renal insufficiency due to progressive parenchymal destruction by multiple
cysts, pulmonary complications due to
lymphangioleiomyomatosis, and
cardiac failure or arrhythmias secondary to
rhabdomyomas. In the last decades, there has been a great progress in understanding the pathophysiology of
TSC-related manifestations, which are mainly linked to the hyperactivation of the so-called
mammalian target of rapamycin (mTOR) pathway, as a consequence of the mutation in 1 of the 2 genes TSC1 or TSC2. This led to the development of new treatment strategies for this disease. In fact, it is now available as a biologically targeted
therapy with
everolimus, a selective mTOR inhibitor, which has been licensed in Europe and USA for the treatment of subependymal giant cell
astrocytomas and
angiomyolipomas in subjects with
TSC. This
drug also proved to benefit other
TSC-related manifestations, including pulmonary
lymphangioleiomyomatosis, cardiac
rhabdomyomas, and presumably epileptic
seizures.
mTOR inhibitors are thus proving to be a systemic
therapy able to simultaneously address different and potentially life-threatening complications, giving the hope of improving life expectation in individuals with
TSC.