In healthy individuals who do not have TSC, the products of the TSC1 and TSC2 gene work together to keep cell division in check. They do this by switching off a component of the cell called mTOR that, if improperly regulated stimulates cell growth and multiplication. In individuals with TSC this switching off mechanism does not work properly and mTOR signals the cells to grow and multiply inappropriately. This can lead to the development of tumours, or overgrowths of cells in many organs of the body. A drug has been developed that can inhibit (work against) mTOR, putting the break on cell division in tumours. Although this drug treatment can shrink kidney tumours in people with TSC, the tumours do not disappear and when treatment is stopped they can regrow.
This 1 year pilot project will test whether cells lacking TSC2 are responsive to another class of drugs that activate a cell process called ‘autophagy’, which means ‘self-eat’. Autophagy is a necessary normal process that ‘cleans’ the cell. This fundamental process is lost in tumour cells in TSC patients. By restoring autophagy function in these cells, the research team lead by Dr Andy Tee will test whether it is possible to reverse (rather than simply halt) the tumour properties of cells lacking TSC2 – turning tumour cells back into normal cells. The data acquired will determine whether this new strategy of therapy could be viable for future TSC clinical trials in the UK.