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Wolfgang Miesbach: Can We ‘Pre‑Tame’ the Immune System to Unlock Better AAV8 FVIII Expression?

Wolfgang Miesbach/LinkedIn

Jun 30, 2026, 02:29

Wolfgang Miesbach: Can We ‘Pre‑Tame’ the Immune System to Unlock Better AAV8 FVIII Expression?

Wolfgang Miesbach, Professor of Medicine at Frankfurt University Hospital, shared on LinkedIn:

“The story of haemophilia gene therapy continues – in China.

Can we ‘pre‑tame’ the immune system to unlock better AAV8 FVIII expression?

A new phase 1 pilot study from Liu et al. (GS001, AAV8‑BDDFVIII) in Signal Transduction and Targeted Therapy tests exactly that: single‑dose, liver‑directed hemophilia A gene therapy plus prophylactic prednisone with or without tacrolimus in 12 adults with severe HA:

Rapid FVIII rise, with expression peaking at 5–7 weeks post‑infusion in both 2×10¹² and 4×10¹² vg/kg cohorts.

In the high‑dose group, median FVIII nearly 60 IU/dL at week 52 and nearly 43 IU/dL at week 104; all six patients stayed at least 29 IU/dL (non‑hemophilia / high mild range).

Annualized bleeding rate and FVIII consumption dropped sharply; in the high‑dose cohort, no bleeds requiring FVIII after gene therapy.

ALT/AST elevations were mostly grade 1–2, and single‑cell RNA‑seq plus in vitro assays suggest prednisone and tacrolimus specifically dampens CD8 T‑cell activation without major CD4 suppression.

Conceptually, this study pushes the idea that pre‑emptive, targeted immunosuppression can help secure higher, more durable FVIII levels at relatively modest AAV8 doses – highly relevant for countries with constrained resources and large haemophilia A populations.”

Wolfgang Miesbach