Effect of the high protein diet challenge on MMA mice treated with vehicle or 1×10¹⁴ vg/kg mLB-001 on PND 1.

(A) Study design. Animals were dosed with vehicle or mLB-001 on PND 1. Nursing dams were kept on the standard 21% protein diet until PND 14, when the diet was switched to a 12% protein diet. Pups were weaned on PND 28 and maintained on the 12% protein diet. At 3 months of age, all surviving animals were switched to the standard chow with 21% protein content and then to a 40% protein diet at 4 months of age. Necropsy was performed at 6 months of age. (B) Kaplan-Meier survival curves of MMA mice. Log-rank test demonstrated significantly better survival of the mLB-001-treated group than the vehicle-treated group (P 0.05). (C) Change in body weight of MMA mice in response to the high protein diet challenge. The body weight of each Mmut-deficient animal was normalized to its weight at the introduction of the 21% protein diet. Females and males were combined due to a lack of significant difference. Animal numbers at each timepoint are indicated above the graph. ** P 0.01, *** P 0.001, **** P 0.0001, mixed-effects analysis with multiple comparisons between vehicle- and mLB-001-treated groups at indicated timepoints. (D) Circulating methylmalonic acid levels in MMA mice. The mLB-001-treated animals maintained lower levels than the vehicle-treated animals in response to the high protein diet challenge.