| First Author | Chung S | Year | 2007 |
| Journal | Mol Genet Metab | Volume | 90 |
| Issue | 2 | Pages | 181-92 |
| PubMed ID | 16979922 | Mgi Jnum | J:117749 |
| Mgi Id | MGI:3697540 | Doi | 10.1016/j.ymgme.2006.08.001 |
| Citation | Chung S, et al. (2007) Effect of neonatal administration of a retroviral vector expressing alpha-l-iduronidase upon lysosomal storage in brain and other organs in mucopolysaccharidosis I mice. Mol Genet Metab 90(2):181-92 |
| abstractText | Mucopolysaccharidosis I (MPS I) due to deficient alpha-l-iduronidase (IDUA) activity results in accumulation of glycosaminoglycans in many cells. Gene therapy could program cells to secrete IDUA modified with mannose 6-phosphate (M6P), and enzyme could be taken up by other cells via the M6P receptor. We previously reported that newborn MPS I mice that were injected intravenously with 10(9) (high-dose) or 10(8) (low-dose) transducing units/kg of a retroviral vector (RV) expressing canine IDUA achieved stable levels of IDUA activity in serum and had reduced disease in heart, eye, ear, and bone in a dose-dependent fashion. However, the dose required for improvement in manifestations of disease in other organs was not reported. High-dose and low-dose RV mice with an average serum IDUA activity of 1037+/-90U/ml (471-fold normal) and 43+/-12U/ml (20-fold normal), respectively, had complete correction of biochemical and pathological evidence of disease in the liver, spleen, kidney, and small intestines. Although mice that received high-dose RV had complete correction of lysosomal storage in thymus, ovary, lung, and testis, correction in these organs was only partial for those that received low-dose RV. Storage in brain was almost completely corrected with high-dose RV, but was not improved with low-dose RV. The correction of disease in brain may be due to diffusion of enzyme from blood. We conclude that high-dose RV prevents biochemical and pathological manifestations of disease in all organs in MPS I mice including brain. |
