Results in AAV-mediated gene therapy trials for subjects infused at a dose of 2 × 10¹² vg/kg (high dose in both trials). (A-B) Of the 2 subjects infused at the highest dose with the AAV2-FIX vector, the first achieved a circulating level of ∼ 10% initially, followed by a gradual fall to the baseline of < 1%. This was accompanied by an asymptomatic rise in liver enzymes that began 4 weeks after vector infusion. The second subject, with a higher pretreatment neutralizing antibody titer to AAV-2, failed to achieve any substantial expression. (C-D) The 2 subjects infused at the highest dose with the AAV8-scFIX vector both achieved circulating levels in the range of 6%-10% initially. (C) The first showed a rise in liver enzymes and fall in FIX levels ∼ 8 weeks after vector infusion, but administration of prednisolone at 60 mg/d normalized liver function tests and arrested the decline in FIX levels, leaving the subject with sustained expression in the range of 2%. (D) In the second subject infused at this dose, liver function tests rose very slightly ∼ 9 weeks after vector infusion, the subject was immediately started on prednisolone, and his circulating FIX level now remains in the range of 5%.²  (C-D) Reprinted from Figure 1E and F in Nathwani et al² with permission.