Tuberous Sclerosis Complex

Tuberous sclerosis complex (TSC) is a multi-system genetic disease seen in about 1:6,000 people. The hallmark of the disorder is hamartomas, benign tumours found in the brain and other organs such as the kidneys, heart, eyes, lungs, and skin. While affecting many organs, neurological features including seizures, autism, developmental delay, and behavioral problems are very common and debilitating. TSC is caused by mutations on either of two genes, TSC1 and TSC2, which encode for the proteins hamartin and tuberin respectively. These proteins act as tumour growth suppressors that appear to regulate both cell proliferation and differentiation.

TSC research has greatly accelerated over the last few years and is considered to be a vital model system that impacts fields of brain development, epilepsy, and autism. A very important recent finding was the inhibition of the mTOR kinase by hamartin/tuberin. Loss of function of either hamartin/tuberin has been shown in multiple human cell types to lead to constitutive activity of the mTOR kinase. While many downstream effectors are now being discovered, inhibition of mTOR by drugs such as rapamycin have been proposed as rational therapies for the neurological and other manifestations of TSC.

Modeling TSC Brain Devl and Hyperexcitability.