Tuberous sclerosis complex: a brave new world?
OBJECTIVE
Tuberous sclerosis complex (TSC) is a multiorgan genetic disease caused by mutations in the TSC1 or TSC2 genes. TSC has been recognized for many years as an important cause of severe neurological disease with patients suffering from epilepsy, developmental delay, autism, and psychiatric problems. During the last year, there have been enormous advances in basic and translational research pertaining to TSC.


RESULTS
In this review, I discuss the basic science findings that position the TSC1 and TSC2 genes as critical regulators of the mammalian target of rapamycin kinase within mammalian target of rapamycin complex 1. In addition, I will discuss the development of new animal models, translational data, and recent clinical trials using mammalian target of rapamycin complex 1 inhibitors such as rapamycin.


CONCLUSIONS
The past few years have seen spectacular advances that have energized TSC-related research and challenged existing symptomatic treatments. Although it remains to be seen whether use of mammalian target of rapamycin complex 1 inhibitors will revolutionize the care of patients with TSC, the application of basic and translational research towards a specific clinical disorder emphasizes the potential and promise of molecular medicine.
Ess
Kevin C
KC
Department of Neurology and Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, Tennessee, USA. kevin.ess@vanderbilt.edu
D000818:Animals; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D015398:Signal Transduction; D020123:Sirolimus / Q000627:therapeutic use; D014157:Transcription Factors / Q000037:antagonists & inhibitors; D014402:Tuberous Sclerosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*
C519509:Crtc1 protein, mouse; D014157:Transcription Factors; D020123:Sirolimus