Hereditary multiple exostoses: are there new plausible treatment strategies?

ABSTRACT

Introduction: Hereditary multiple exostoses (HME) is a rare congenital pediatric disorder characterized by osteochondromas forming next to the growth plates in young patients. The osteochondromas cause multiple health problems that include skeletal deformities and chronic pain. Surgery is used to remove the most symptomatic osteochondromas but because of their large number, many are left in place, causing life-long problems and increasing the probability of malignant transformation. There is no other treatment to prevent or reduce osteochondroma formation at present.

Areas covered: Recent studies reviewable through PubMed are providing new insights into cellular and molecular mechanisms of osteochondroma development. The resulting data are suggesting rational and plausible new therapeutic strategies for osteochondroma prevention some of which are being tested in HME animal models and one of which is part of a just announced clinical trial.

Expert commentary: This section summarizes and evaluates such strategies and points also to possible future alternatives.

KEYWORDS:

• Hereditary Multiple Exostoses
• Multiple Osteochondromas
• EXT1
• EXT2
• Heparan sulfate
• signaling proteins and pathways
• drug treatment

Article Highlights

• Hereditary Multiple Exostoses is a rare pediatric disorder characterized by growth plate-associated osteochondromas that cause a number of health problems

• HME is linked to EXT mutations and ensuing deficiency in heparan sulfate (HS), a component of cell surface and matrix proteoglycans that regulates many fundamental processes

• This editorial summarizes and analyzes recent studies on pathogenic changes caused by the HS deficiency and leading to osteochondroma formation

• Those studies suggest plausible new and specific treatment strategies by which osteochondroma formation could be prevented or reduced

This box summarizes key points contained in the article.

Acknowledgments

I would like to express gratitude to the many colleagues participating in the studies, to collaborators providing reagents and mouse lines, and to Dr. E. Koyama in particular for contributions to Figure 1 model. Due to the concise nature of this review, not all relevant and deserving literature and authors could be cited. We would like to acknowledge the passionate efforts of the Multiple Hereditary Exostoses Research Foundation (http://www.mherf.org/), a private non-profit organization dedicated to the support of families and patients with HME and to advocating HME public awareness and biomedical research.

Disclosure statement

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Declaration of interests

Dr. Pacifici holds a patent on targeting heparanase as a possible therapeutic for HME. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

The original studies in the author’s laboratory upon which this review is based were supported by the NIAMS grant R01AR061758. The content of this article is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health.