Targeting the mTOR signalling pathway for prevention and therapy of tuberous sclerosis in mouse models

Tuberous sclerosis is an autosomal dominant genetic disorder characterised by the development of benign tumours in multiple organs. It is caused by mutations in the TSC1 or TSC2 tumour suppressor gene, leading to hyperactivation of mTOR signalling in affected tissues. Rapamycin and its analogues are mTOR inhibitors and have been used to treat tuberous sclerosis in both pre-clinical and clinical trials. However, tumours usually relapse after drug withdrawal. The aims of this project were to identify novel agents and strategies for prevention and therapy of tuberous sclerosis using mouse models. First T2 weighted MRI was evaluated for assessment of renal lesions in Tsc1+/- and Tsc2+/- mouse models. MRI identified all types of Tsc-associated renal lesions in both Tsc mouse models. The smallest detectable lesions were