Sirolimus for Angiomyolipoma in Tuberous Sclerosis Complex or Lymphangioleiomyomatosis

In this open-label trial, patients with tuberous sclerosis or lymphangioleiomyomatosis — conditions with constitutive activation of signaling by the mammalian target of rapamycin (mTOR) — received rapamycin (now called sirolimus) for 1 year and were observed for an additional year. Angiomyolipomas regressed with sirolimus therapy but generally increased after therapy was stopped. Pulmonary function improved after treatment in some patients. Suppression of mTOR signaling may hold therapeutic promise in these conditions. Angiomyolipomas regressed with sirolimus therapy but generally increased after therapy was stopped. Pulmonary function improved after treatment in some patients. Suppression of mTOR signaling may hold therapeutic promise in these conditions. The tuberous sclerosis complex, a tumor-suppressor syndrome caused by mutations in the tuberin gene ( TSC2 ) or the hamartin gene ( TSC1 ), is characterized by hamartomas in organs including the brain, kidney, lung, skin, and heart. 1 Angiomyolipomas — tumors rich in fat, muscle, and blood vessels that can hemorrhage or infiltrate the kidney, leading to renal failure — develop in approximately 80% of patients. 2 Lymphangioleiomyomatosis, the major pulmonary manifestation in women with the tuberous sclerosis complex, is a progressive lung disease characterized by infiltration of smooth-muscle cells and formation of parenchymal cysts. 3 Sporadic lymphangioleiomyomatosis can develop in women . . .