Fig. 4: Long-term sustained complete rescue of severe MSUD phenotype in Bckdha−/− mice.
From: Neonatal gene therapy achieves sustained disease rescue of maple syrup urine disease in mice
Mice were injected at 1014 vg/kg with AAV8-EF1α-hBCKDHA. a Weight curves for males (Bckdha−/− n = 6, Bckdha+/− n = 3, Bckdha+/+ n = 3) and b females (Bckdha−/− n = 3, Bckdha+/− n = 8, Bckdha+/+ n = 6) for all injected mice. c Plasma leucine concentrations for non-injected Bckdha−/− newborns (n = 3) and at 6 months for injected mice, Bckdha−/−, Bckdha+/−, and Bckdha+/+ (n = 5 each). d Vector genome copy number (VGCN), e human BCKDHA (hBCKDHA) mRNA, and f BCKDHA protein levels in the liver, heart, and brain in mice sacrificed 6 months after neonatal injection (Bckdha−/− injected n = 5, controls: Bckdha−/− n = 1 non-injected and sacrificed at 1 week + 1 non-injected Bckdha+/+ sacrificed at 6 months for western blots). Analyses were performed in triplicate. The antibody detected both the human BCKDHA and the murine BCKDHA proteins. g Kaplan–Meier curves for all injected Bckdha−/− mice (n = 9) (blue line) during the first 6 months. The red dash line represents the maximum survival of untreated Bckdha−/− mice. All data are shown as mean ± SD. Source data are provided as a Source data file.
