On the Horizon for Metabolic Bone Disease in Children

These inborn errors of metabolism cannot currently be cured. With respect to spinal disease, current therapies are aimed at reducing the rate of progression of disease, optimizing function, and treating complications (e.g., spinal compression, deformity, and instability). Future directions of treatment include the following:

• Substrate reduction: In the mucopolysaccharidosis disorders, drugs (e.g., genistein) would be used to reduce the rate of formation of the glycosaminoglycans that build up in the connective tissues, leading to damage (38, 40).
• Gene therapy: An ultimate aim would be modify or replace the faulty gene responsible for these disorders (34). Recent reports have indicated that successful disease modification can be achieved after gene therapy treatment for mucopolysaccharidosis type III (Sanfilippo syndrome) in animal models (13). Human trials in Sanfilippo syndrome are underway that involve direct instillation of the viral vector carrying the gene into the brain. In Sanfilippo syndrome, in contrast with the other mucopolysaccharidosis, the brain is affected far more than the musculoskeletal system.
• Reduction of inflammation: Animal models have shown that much of the connective tissue damage in the mucopolysaccharidoses is mediated via inflammation. New anti-inflammatory agents have shown to reduce the rate of tissue damage when used alone or in combination with other treatments such as enzyme replacement therapy (30).