Current therapies for Morquio A syndrome and their clinical outcomes

ABSTRACT

Introduction: Morquio A syndrome is characterized by a unique skeletal dysplasia, leading to short neck and trunk, pectus carinatum, laxity of joints, kyphoscoliosis, and tracheal obstruction. Cervical spinal cord compression/inability, a restrictive and obstructive airway, and/or bone deformity and imbalance of growth, are life-threatening to Morquio A patients, leading to a high morbidity and mortality. It is critical to review the current therapeutic approaches with respect to their efficacy and limitations.

Areas covered: Patients with progressive skeletal dysplasia often need to undergo orthopedic surgical interventions in the first two decades of life. Recently, we have treated four patients with a new surgery to correct progressive tracheal obstruction. Enzyme replacement therapy (ERT) has been approved clinically. Cell-based therapies such as hematopoietic stem cell therapy (HSCT) and gene therapy are typically one-time, permanent treatments for enzyme deficiencies. We report here on four Morquio A patients treated with HSCT approved in Japan and followed for at least ten years after treatment. Gene therapy is under investigation on mouse models but not yet available as a therapeutic option.

Expert opinion: ERT and HSCT in combination with surgical intervention(s) are a therapeutic option for Morquio A; however, the approach for bone and cartilage lesion remains an unmet challenge.

KEYWORDS:

• Morquio A
• ERT
• HSCT
• gene therapy
• orthopedic surgery
• tracheal obstruction

Article highlights

• Description of clinical effect and limitations of current therapies for Morquio A.

• Limited improvement of ERT and HSCT in bone.

• Cases with severe tracheal obstruction by a new tracheal surgery.

• Gene therapy as a new therapeutic option for Morquio A.

This box summarizes key points contained in the article.

Declaration of interest

The content of the article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other sponsors. Editorial assistance to the manuscript was provided by Michelle Stofa at Nemours/Alfred I. duPont Hospital for Children. The authors have 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

This work was supported by grants from the Austrian MPS Society and International Morquio Organization (Carol Ann Foundation). This work was also supported by Japanese MPS Family Society. Y Suzuki and KE Orii were supported by the Ministry of Health, Labor, and Welfare of Japan. RW Mason and S Tomatsu were supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences under grant number P30GM114736. S Tomatsu received a grant from the National Institutes of Health (R01HD065767).