Effects of lithium administration on vertebral bone disease in mucopolysaccharidosis I dogs

Modeling skeletal dysplasia in Hurler syndrome using patient-derived bone marrow osteoprogenitor cells

“…Essential steps in the substitution process include apoptosis of hypertrophic chondrocytes, resorption of mineralized ECM, and homing of blood vesselassociated progenitor cells producing bone, marrow stroma, and marrow adipose tissue (16,21). Accordingly, available studies on the mechanisms underlying the abnormal retention of cartilage observed in MPS IH endochondrally formed bone (12)(13)(14)(22)(23)(24) are mainly focused on the effects of GAG accumulation on this sequence of events (10,14,25). Recent evidence, however, demonstrates that endochondral ossification is a more complex phenomenon in which specific chondrocyte subsets escape death and undergo a phenotypic shift that leads to the direct remodeling of cartilage into other skeletal tissues (26)(27)(28)(29).…”

“…Experimental work on MPS IH transgenic mice and other spontaneously occurring dog and cat models supports the hypothesis that dysostosis multiplex may result from early developmental changes that become clinically apparent after birth (10,11). In particular, many studies identified inappropriate retention of cartilage at sites of bone formation as a recurrent pathological feature of the disease (10,(12)(13)(14). This suggests that HS and DS accumulation during skeletal development and growth interferes with the replacement of cartilage anlage with bone and bone marrow (BM), a process that relies on endochondral ossification and, as recently shown, on the direct phenotypic switch of the cartilaginous tissue (15).…”

Evaluation of tendon and ligament microstructure and mechanical properties in a canine model of mucopolysaccharidosis I

“…Treatment with adalimumab, a tumor necrosis factor‐alpha (TNF‐α) inhibitor, was also found to improve joint range‐of‐motion in MPS I patients in both upper and lower extremities 57 . Oral lithium carbonate treatment was reported to reduce joint swelling and improve mobility in MPS I dogs 58 . Preclinical studies suggest that intra‐articular delivery of therapeutic agents may be a promising alternative to systemic treatments due to increased local bioavailability of drugs to joint tissues 59,60 .…”

“…57 Oral lithium carbonate treatment was reported to reduce joint swelling and improve mobility in MPS I dogs. 58 Preclinical studies suggest that intra-articular delivery of therapeutic agents may be a promising alternative to systemic treatments due to increased local bioavailability of drugs to joint tissues. 59,60 Notably, none of these studies specifically evaluated effects on ligament and tendon function; however, our group recently reported dose-dependent improvements in CCL mechanical properties in response to systemic ERT in MPS VII dogs, and these were associated with improvements in mobility.…”