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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
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