Paradigm shift in the treatment of tuberous sclerosis: Effectiveness of everolimus.

ABSTRACT

Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterised by abnormal cell proliferation and differentiation that affects multiple organs and can lead to the growth of hamartomas. Tuberous sclerosis complex is caused by the disinhibition of the protein mTOR (mammalian target of rapamycin). In the past, various therapeutic approaches, even if only symptomatic, have been attempted to improve the clinical effects of this disease. While all of these therapeutic strategies are useful and are still used and indicated, they are symptomatic therapies based on the individual symptoms of the disease and therefore not fully effective in modifying long-term outcomes. A new therapeutic approach is the introduction of allosteric inhibitors of mTORC1, which allow restoration of metabolic homeostasis in mutant cells, potentially eliminating most of the clinical manifestations associated with Tuberous sclerosis complex. Everolimus, a mammalian target of the rapamycin inhibitor, is able to reduce hamartomas, correcting the specific molecular defect that causes Tuberous sclerosis complex. In this review, we report the findings from the literature on the use of everolimus as an effective and safe drug in the treatment of TSC manifestations affecting various organs, from the central nervous system to the heart.