Previtali Roberto, Prontera Giorgia, Alfei Enrico, Nespoli Luisa, Masnada Silvia, Veggiotti Pierangelo, Mannarino Savina
Pediatric Neurology Unit, Buzzi Children's Hospital, Milan, Italy; Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Pharmacol Res. 2023 Sep;195:106884. doi: 10.1016/j.phrs.2023.106884. Epub 2023 Aug 6.
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.
结节性硬化症（TSC）是一种常染色体显性疾病，其特征为细胞增殖和分化异常，可累及多个器官并导致错构瘤生长。结节性硬化症由蛋白质mTOR（雷帕霉素哺乳动物靶点）的抑制解除引起。过去，人们尝试了各种治疗方法，即便只是对症治疗，以改善该疾病的临床疗效。虽然所有这些治疗策略都有用且仍在使用和推荐，但它们都是基于疾病的个体症状的对症治疗，因此在改变长期预后方面并不完全有效。一种新的治疗方法是引入mTORC1的变构抑制剂，这可以恢复突变细胞中的代谢稳态，有可能消除与结节性硬化症相关的大多数临床表现。依维莫司是一种雷帕霉素抑制剂的哺乳动物靶点，能够减少错构瘤，纠正导致结节性硬化症的特定分子缺陷。在本综述中，我们报告了文献中关于依维莫司作为一种有效且安全的药物用于治疗从中枢神经系统到心脏等各个器官的TSC表现的研究结果。
