Mucopolysaccharidosis type IVA (MPS IVA) results from a deficiency of the enzyme N-acetylgalactoseamine- 6-sulfate sulfatase. This enzyme is required for the breakdown of complex sugars called “glycosaminoglycans (GAGs).” GAGs are normally found throughout the body, including bones and joints, and are constantly broken down and replaced with new GAGs. In MPS IVA, GAGs cannot be broken down properly, resulting in their abnormal accumulation. Patients with MPS IVA often present with systemic skeletal abnormalities (bone deformities, short stature, and spinal cord compression).
Several treatment strategies for MPS have been tested. These treatments showed limited effect on bone and brain involvement. Recently, an enzyme replacement therapy strategy using modified long-circulating β- glucuronidase on MPS VII mice was shown to almost completely correct brain storage of GAGs and to reduce storage materials substantially in bone. Given the success of this therapy in MPS VII mice, the question of whether the modified enzyme also works to improve bone pathology is of great interest in MPS IVA mice. We have developed an assessment method to evaluate skeletal pathology quantitatively in MPS mice. We expect the new treatment strategy to improve bone lesions in MPS IVA, leading to increased mobility and a better quality of life.
– Shunji Tomatsu, MD, PhD
Nemours Children’s Clinic – Delaware Valley of the Nemours Foundation