Fig. 7: Durable gene-corrected cell therapy for Pompe disease requires persistent proliferative cells.

a Plots showing the degree of phenotypically normal cardiac tissue when either 10 billion non-proliferative single- or double-corrected cells are dosed or 0.1 billion proliferative single- or double-corrected cells are dosed. For these plots, the GAA production for double-corrected cells is 150% excess that of single corrected cells for four different half-lives of dosed cells. For long-lasting correction, proliferative progenitor cells need to have a half-life exceeding 100 days. b Heatmap showing the proliferative cell dose (assuming double-corrected cells with 75% excess GAA production compared to single-corrected cells) against the half-life of dosed cells. If the dosed cells have a half-life similar to endogenous hepatocytes, a 75 million cell dose is sufficient for matching ERT. c Heatmap showing the proliferative cell dose (assuming that the dosed cells have 250-day half-life) against the GAA production rate of dosed cells, demonstrating that dose has a higher effect on therapeutic efficacy than GAA production gained from double correction. d Heatmap showing that the GAA production against the half-life of the dosed cells (assuming that 250 million cells were dosed), indicating that the half-life of the dosed cells has a higher effect on therapeutic efficacy than the GAA production gained from double correction. e Sensitivity analysis for model parameters relevant to cell therapy. In addition to growth and differentiation rates of the transplanted cells, outcomes are highly sensitive to the proliferative cell half-life, cell dose and excess GAA produced by double gene correction. These later parameters, relevant to the design of therapy with autologous gene-corrected cells, are bolded.