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AB0137 Characterization of joint disease in mucopolysaccharidosis type I mice and the effects of enzyme replacement therapy
  1. P.G. Oliveira1,
  2. G. Baldo2,
  3. F.Q. Mayer2,
  4. B. Martinelli2,
  5. L. Meurer3,
  6. R. Giugliani2,
  7. U. Matte2,
  8. R.M. Xavier1
  1. 1Rheumatology, Universidade Federal Do Rio Grande Do Sul
  2. 2Genetics Therapy Center, hospital de Clinicas de Porto Alegre
  3. 3Pathology, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil


Background Mucopolysaccharidosis type I (MPS I) is a lysosomal disorder caused by deficiency of alpha-L-iduronidase, which leads to storage of the glycosaminoglycans heparan sulphate and dermatan sulphate. Patients with MPS I present destructive changes in their joints in a process not well understood. The MPS I animal model is a useful tool to study the disease pathogenesis; however the changes in the MPS I joints were never investigated in more detail. This work aimed to describe the joint disease progression in the murine model of MPS I.

Objectives Create a score to characterize the histological abnormalities in the MPS I mice knee joints. It allowed us to systematically study the age of onset of joint disease, as well as its progression. In addition, based on the results from the histological analysis, we tried to find possible mechanisms responsible for the disease. Finally, we verified if intravenous ERT was effective in preventing this complication of MPS I.

Methods Normal (wild type) and untreated MPS I mice were killed at different time points (2, 4, 6, 8, and 12 months). In addition, some MPS I mice were treated with enzyme replacement therapy (ERT) and sacrificed at 6 months. The knee joints were collected and hematoxylin and eosin staining was used to evaluate the articular architecture. Safranin-O staining was used to analyze proteoglycans (PGs) content. In addition we analyzed the expression of matrix-degrading metalloproteinases (MMPs), MMP-2 and -9, by immunohistochemistry.

Results MPS I mice did not present any significant joint changes at 2 and 4 months. From 6 months, we observed progressive joint alterations, including presence of synovial inflammatory infiltrate, destruction and thickening of the cartilage extracellular matrix and PGs depletion. Also, we observed an increase in the expression of MMP-2 and -9, which could explain the degenerative changes. We also investigated the effect of ERT when started at 2 months, which showed no benefits, suggesting that the poorly vascularized cartilage is difficult to reach, and an ancillary therapy might be needed for patients.

Conclusions Our results suggest that the degenerative joint and bone disease in MPS I animals presents some similarities to osteoarthritis. More important, our results evidence the importance of understanding the pathologic processes of joint disease associated with MPS I in the search for new treatments.

Disclosure of Interest None Declared

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