Cathepsin K: both a likely biomarker and a new therapeutic target in lymphangioleiomyomatosis?

Abstract

Lymphangioleiomyomatosis (LAM) is a rare disease characterized by cystic lung destruction and lymphangiomas and is associated with a high risk of osteoporosis-related bone fractures. Its diagnosis is based on pulmonary anatomo-pathological criteria combined with chest computed tomography. Vascular endothelial growth factor-D is the only serum diagnostic biomarker used in clinical practice, while inhibition of the mammalian target of rapamycin (mTOR) pathway by rapamycin is currently the only reference therapy for LAM. Human cathepsin K (CatK), a potent collagenase predominantly found in osteoclasts, is considered a valuable target for anti-osteoporosis and bone cancer therapy. Recently, CatK, which is overexpressed in lung cysts, was proposed as a putative LAM biomarker. Moreover, CatK may play a role in the LAM pathophysiology by contributing to pulmonary cystic destruction and bone degradation. Accordingly, targeting the collagenolytic activity of CatK by exosite-binding inhibitors, in combination with mTOR inhibition, could represent an innovative therapeutic option for reducing lung destruction in LAM.

Keywords

Bourneville’s disease / biomarker / cathepsin / protease inhibitors / lung / lymphangioleiomyomatosis / protease / rapamycin (Sirolimus)

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