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Marchand-Adam et al. Rare Dis Orphan Drugs J 2023;2:3 Rare Disease and
DOI: 10.20517/rdodj.2022.24
Orphan Drugs Journal
Perspective Open Access
Cathepsin K: both a likely biomarker and a new
therapeutic target in lymphangioleiomyomatosis?
3
1,2
1,2
Sylvain Marchand-Adam 1,2,3 , Marion Pronost , Ahlame Saidi , Fabien Lecaille , Gilles Lalmanach 1,2
1
University of Tours, Tours 37000, France.
2
INSERM, UMR1100, Research Center for Respiratory Diseases (CEPR), Team “Proteolytic Mechanisms in Inflammation”, Tours
37000, France.
3
The University Hospital Center of Tours (CHRU Tours), Pulmonology Department, Tours 37000, France.
Correspondence to: Prof. Gilles Lalmanach. INSERM UMR 1100, Research Center for Respiratory Diseases (CEPR), University of
Tours, Faculty of Medicine, 10 Boulevard Tonnellé, F-37032 Tours cedex, Tours 37000, France.
E-mail: gilles.lalmanach@univ-tours.fr
How to cite this article: Marchand-Adam S, Pronost M, Saidi A, Lecaille F, Lalmanach G. Cathepsin K: both a likely biomarker and
a new therapeutic target in lymphangioleiomyomatosis? Rare Dis Orphan Drugs J 2023;2:3.
https://dx.doi.org/10.20517/rdodj.2022.24
Received: 23 Nov 2022 First Decision: 30 Jan 2023 Revised: 17 Feb 2023 Accepted: 3 Mar 2023 Published: 13 Mar 2023
Academic Editors: Jacques S Beckmann, Bridget Bax Copy Editor: Ying Han Production Editor: Ying Han
Abstract
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.
Keywords: bourneville’s Disease, biomarker, cathepsin, protease inhibitors, lung, lymphangioleiomyomatosis,
protease, rapamycin (Sirolimus)
© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.
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