Biomarkers for prediction of skeletal disease progression in mucopolysaccharidosis type I

• Published in: JIMD reports 2021-03, Vol.58 (1), p.89-99
• Main Authors: Lund, Troy C., Doherty, Terence M., Eisengart, Julie B., Freese, Rebecca L., Rudser, Kyle D., Fung, Ellen B., Miller, Bradley S., White, Klane K., Orchard, Paul J., Whitley, Chester B., Polgreen, Lynda E.
• Format: Article
• Language: English
• Subjects: Age; Arthritis; biomarker; Biomarkers; bone; Bone surgery; Cartilage; Clinical trials; Cytokines; Genetic disorders; Hip dislocation; Hurler; Immunoassay; inflammation; Metabolic disorders; mucopolysaccharidosis; Observational studies; Orthopedics; Osteoarthritis; Pediatrics; Plasma; Quality of life; Regression analysis; Research Report; Research Reports; Scheie; Standard scores; Statistical analysis; Tumor necrosis factor-TNF; Urine
• ISSN: 2192-8312; 2192-8304; 2192-8312
• DOI: 10.1002/jmd2.12190

Background Orthopedic disease progresses in mucopolysaccharidosis type I (MPS I), even with approved therapies and remains a major factor in persistent suffering and disability. Novel therapies and accurate predictors of response are needed. The primary objective of this study was to identify surrogate biomarkers of future change in orthopedic disease. Methods As part of a 9‐year observational study of MPS I, range‐of‐motion (ROM), height, pelvic radiographs were measured annually. Biomarkers in year 1 were compared to healthy controls. Linear regression tested for associations of change in biomarkers over the first year with change in long‐term outcomes. Results MPS I participants (N = 19) were age 5 to 16 years and on average 6.9 ± 2.9 years post treatment initiation. Healthy controls (N = 51) were age 9 to 17 years. Plasma IL‐1β, TNF‐α, osteocalcin, pyridinolines, and deoxypyridinolines were higher in MPS than controls. Within MPS, progression of hip dysplasia was present in 46% to 77%. A 1 pg/mL increase in IL‐6 was associated with −22°/year change in ROM (−28 to −15; P