EXPECTED THERAPEUTIC MECHANISM

Complexes of the products of the causative genes of tuberous sclerosis complex (TSC)—TSC1 and TSC2—inhibit mTORC1 activity via Rheb, a low-molecular-weight protein. Abnormal enhancement of mTORC1 activity is one cause of a variety of pathologies and may be caused by mutations in either of these genes. mTORC1 inhibition by sirolimus has been shown to suppress TSC symptoms directly and effectively. Today, this drug is indicated for TSC with comorbid lymphangioleiomyomatosis (TSC-LAM) in Japan’s national health insurance, as well as skin lesions, such as facial angiofibroma.

SIROLIMUS’ EFFECTS IN TSC

In LAM, sirolimus administration has proven effective in preventing and stabilizing declines in respiratory function, reducing counts of severe cases requiring lung transplantation. In addition, sirolimus gel preparations used to treat skin lesions have demonstrated benefits, such as shrinking facial angiofibroma, improving skin tone (redness), and concealing vitiligo. In every case, however, sirolimus neither eliminates nor heals the lesions in question, and symptoms will relapse and progress upon its discontinuation.