Identification of novel targets for the treatment of tuberous sclerosis complex
Embargo Date
2028-02-26
OA Version
Citation
Abstract
Tuberous Sclerosis Complex (TSC) is an autosomal dominant disease characterized by a loss-of-function mutation in genes coding for TSC1 and TSC2. Hamartin and Tuberin are encoded by TSC1 and TSC2, respectively, forming an inhibitory protein complex that suppresses the mechanistic target of rapamycin complex 1 (mTORC1). Clinical presentation of TSC varies across patients. This rare genetic disease causes benign tumors and lesions in various organs, leading to multifarious physiological disruptions. Rapamycin is the only FDA-approved therapy for TSC patients. This drug is an mTORC1 allosteric inhibitor that shrinks brain and kidney tumors; however, several clinical trials have shown that tumors regrow when therapy is interrupted, suggesting that novel and more durable therapies are critical unmet clinical needs in TSC. The aim of this study is to determine the pathogenetic role of selected long noncoding RNAs (lncRNAs) that show remarkable changes in expression in TSC kidney and brain tumors compared to normal tissues. Future studies should evaluate the therapeutic potential of targeting lncRNA genes in TSC.
Description
2025