Sirolimus Treatment for Pulmonary Lymphangioleiomyomatosis

Background: Lymphangioleiomyomatosis (LAM) is a rare disease characterized by abnormal proliferation of smooth-muscle cells within the lung (1) that are responsible for the cystic destruction of lung parenchyma, leading to chronic respiratory failure (2). No effective treatment, except for lung transplantation, is available. Abdominal tumors (renal angiomyolipomas, lymphangioleiomyomas, and enlarged lymph nodes) are frequently associated with lung involvement. Recently, loss-of-function mutations in the tumor suppressor genes tuberous sclerosis 1 and 2 (TSC1 and TSC2, respectively) have been described in LAM (3). In vitro studies on LAM smooth-muscle cells have shown that mutation on the TSC1–TSC2 complex dysregulates the activation of ribosomal protein S6 kinase …