Rare Disease and Orphan Drugs Journal
Cover Picture: Lymphangioleiomyomatosis (LAM) is a rare disease that is 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 anatomopathological criteria combined with chest computed tomography. VEGF-D is the only serum diagnostic biomarker used in the clinic, while inhibition of the 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 as 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 take part in the LAM pathophysiology by participating in pulmonary cystic destruction and bone degradation. Accordingly, targeting 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.
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