Bone Growth Induction in Mucopolysaccharidosis IVA Mouse.
Estera RintzAngélica María Herreño-PachónBetul CelikFnu NidhiShaukat KhanEliana Benincore-FlórezShunji TomatsuPublished in: International journal of molecular sciences (2023)
Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is caused by a deficiency of the N-acetylgalactosamine-6-sulfate-sulfatase (GALNS) enzyme, leading to the accumulation of glycosaminoglycans (GAG), keratan sulfate (KS) and chondroitin-6-sulfate (C6S), mainly in cartilage and bone. This lysosomal storage disorder (LSD) is characterized by severe systemic skeletal dysplasia. To this date, none of the treatment options for the MPS IVA patients correct bone pathology. Enzyme replacement therapy with elosulfase alpha provides a limited impact on bone growth and skeletal lesions in MPS IVA patients. To improve bone pathology, we propose a novel gene therapy with a small peptide as a growth-promoting agent for MPS IVA. A small molecule in this peptide family has been found to exert biological actions over the cardiovascular system. This work shows that an AAV vector expressing a C-type natriuretic (CNP) peptide induces bone growth in the MPS IVA mouse model. Histopathological analysis showed the induction of chondrocyte proliferation. CNP peptide also changed the pattern of GAG levels in bone and liver. These results suggest the potential for CNP peptide to be used as a treatment in MPS IVA patients.
Keyphrases
- replacement therapy
- bone mineral density
- end stage renal disease
- ejection fraction
- small molecule
- chronic kidney disease
- newly diagnosed
- soft tissue
- mouse model
- gene therapy
- bone loss
- prognostic factors
- smoking cessation
- signaling pathway
- early onset
- case report
- combination therapy
- extracellular matrix
- protein protein