| First Author | Reiss J | Year | 2019 |
| Journal | Hum Genet | Volume | 138 |
| Issue | 4 | Pages | 355-361 |
| PubMed ID | 30810871 | Mgi Jnum | J:336726 |
| Mgi Id | MGI:7490439 | Doi | 10.1007/s00439-019-01992-z |
| Citation | Reiss J (2019) Molybdenum cofactor deficiency type B knock-in mouse models carrying patient-identical mutations and their rescue by singular AAV injections. Hum Genet 138(4):355-361 |
| abstractText | Molybdenum cofactor deficiency is an autosomal, recessively inherited metabolic disorder, which, in the absence of an effective therapy, leads to early childhood death due to neurological deterioration. In type A of the disease, cyclic pyranopterin monophosphate (cPMP) is missing, the first intermediate in the biosynthesis of the cofactor, and a biochemical substitution therapy using cPMP has been developed. A comparable approach for type B of the disease with a defect in the second step of the synthesis, formation of molybdopterin, so far has been hampered by the extreme instability of the corresponding metabolites. To explore avenues for a successful and safe gene therapy, knock-in mouse models were created carrying the mutations c.88C>T (p.Q30X) and c.726_727delAA, which are also found in human patients. Recombinant adeno-associated viruses (rAAVs) were constructed and used for postnatal intrahepatic injections of MoCo-deficient mice in a proof-of-concept approach. Singular administration of an appropriate virus dose in 60 animals prevented the otherwise devastating phenotype to a variable extent. While untreated mice did not survive for more than 2 weeks, some of the treated mice grew up to adulthood in both sexes. |
