Pathogenesis and treatment of spine disease in the mucopolysaccharidoses

Abstract

The mucopolysaccharidoses (MPS) are a family of lysosomal storage disorders characterized by deficient activity of enzymes that degrade glycosaminoglycans (GAGs). Skeletal disease is common in MPS patients, with the severity varying both within and between subtypes. Within the spectrum of skeletal disease, spinal manifestations are particularly prevalent. Developmental and degenerative abnormalities affecting the substructures of the spine can result in compression of the spinal cord and associated neural elements. Resulting neurological complications, including pain and paralysis, significantly reduce patient quality of life and life expectancy. Systemic therapies for MPS such as hematopoietic stem cell transplantation and enzyme replacement therapy have shown limited efficacy for improving spinal manifestations in patients and animal models, and there is therefore a pressing need for new therapeutic approaches that specifically target this debilitating aspect of the disease. In this review, we examine how pathological abnormalities affecting the key substructures of the spine – the discs, vertebrae, odontoid process and dura – contribute to the progression of spinal deformity and symptomatic compression of neural elements. Specifically, we review current understanding of the underlying pathophysiology of spine disease in MPS, how the tissues of the spine respond to current clinical and experimental treatments, and discuss future strategies for improving the efficacy of these treatments.

RNA sequencing identifies gene regulatory networks controlling extracellular matrix synthesis in intervertebral disk tissues

“…Frozen tissue biopsies were ground into a powder using a mortar and pestle and homogenized in Qiazol reagent (Qiagen, Hilden, Germany) and homogenized. Total RNA was extracted from research biopsies based on previous methods 24,25 using the miRNeasy minikit (Qiagen) and quantified using the NanoDrop 2000 spectrophotometer (Thermo Fischer Scientific, Wilmington, DE). For samples selected for next generation sequencing, RNA integrity was assessed using the Agilent Bioanalyzer DNA 1000 chip (Invitrogen, Carlsbad, CA).…”

Functional Independence of Pediatric Patients With Mucopolysaccharidoses

“… 5 , 7 The nervous system is also commonly affected in some types of MPS, and results in the occurrence of neural and/or spinal cord compression, eventually leading to cognitive impairment. 8 , 9 These changes are progressive and have a significant impact on the functional independence of the individuals affected. 10 …”

Orthopaedic challenges for mucopolysaccharidoses

“…Spine involvement is common in the majority of MPS, although with great variability [ 4 ]. Flattened vertebral bodies (platyspondyly) are a typical feature of dysostosis.…”