Tuberous sclerosis complex (TSC) is a rare condition which results in the buildup of tumors in the skin, kidneys, brain, as well as other organs. Although the tumors are not generally cancerous, they can cause a range of symptoms. TSC is caused by mutations in TSC1 and TSC2. Symptoms of this condition include developmental delay, seizures, skin abnormalities, and kidney disease.
It has long been understood that the mutations in the TSC genes affect mTORC1, making it hyperactive and resulting in progression of disease. However, some patients only partially responded to therapies which targeted mTORC1, making researchers suspicious that some other mechanism could be involved in this condition.
New Research
Some previous studies have indicated that the accumulation of glycogen may be a factor in this disease. Even though glycogen is not usually toxic, an excessive amount can cause damage.
Scientists at the Baylor College of Medicine sought to uncover more. Their findings were published in the Proceedings of the National Academy of Sciences.
They confirmed that there are high levels of glycogen in mouse models and human patients with the disease. Additionally, their research indicated that there had to be another mechanism causing glycogen to accumulate that was unrelated to mTORC1.
This research team also discovered that cells affected by the disease had fewer lysosomes. As lysosomes are responsible for clearing the cell of waste, a decreased number often is an indication of disease. This could be a clue into what other mechanism is involved in this condition.
While we still don’t completely understand tuberous sclerosis, these findings have provided crucial new information regarding this disease. We now know not all mutations of TSC2 are the same. That means that the disease manifests differently in different patients. As a result, different treatments will be more effective for different patients.
Looking Forward
These new findings don’t mean that our past findings were wrong- simply that they were incomplete. TSC mutations are still clearly the cause of this condition. However, we now understand that these TSC mutations manifest in different ways which means they may affect mTORC1 or they may not.
Hopefully, this new understanding will lead to the development of new treatments for this disease. These new developments will be especially important for patients who only partially responded to treatments targeting mTORC1.
You can read more about these new findings in tuberous sclerosis here.
