[Abstract]

One of the biggest challenges of drug discovery is to ensure the correlation between in vitro activity and clinical efficacy. As a first step to addressing the big challenges, animal models can be a valuable and predictable bridges between in vitro drug discovery and early clinical evaluation. In particular, the importance of the disease model becomes greater for drug development of rare disease.

Mucopolysaccharidosis type II (MPSII) also called hunter syndrome, is a rare, multisystemic progressive lysosomal storage disease caused by deficiency of iduronate 2-sulfatase (IDS). Accumulation of the glycosaminoglycans (GAGs) result in a broad range of disease manifestations. Notably, central nervous system (CNS) involvements like neuronal regression are observed in 70 % of the patients. MPS II mice were generated and used in preclinical studies that directly target the replacement of IDS protein to the entire body or the brain. These preclinical studies provided promising results and based on the findings, the clinical trials were successfully completed. Furthermore, we firstly demonstrate that the heparan sulfate in CSF as a useful clinical biomarker for neuropathology using IDS KO mice. These results demonstrate the importance and usefulness of animal models for drug development.