Wolfgang Miesbach: Human Tissue Study Sheds Light on AAV Gene Therapy Safety
Wolfgang Miesbach, Professor of Medicine at Frankfurt University Hospital, shared a post on LinkedIn:
“First human tissue data after cardiotoxicity from AAV gene therapy in Duchenne — a 17-year-old with DMD received delandistrogene moxeparvovec, the first commercially approved gene therapy for the disease.
Ben Samelson-Jones, Lindsey George, and colleagues (CHOP) now report the first cardiac and skeletal-muscle biopsy analysis after cardiotoxic effects:
Day 2: myocarditis, symptomatic atrial fibrillation, mild thrombotic microangiopathy.
Day 42: troponin I rising again, cardiac function deteriorating – intravenous methylprednisolone on top of prednisone and sirolimus. The delayed toxicity is attributed to an adaptive immune response against the AAV capsid.
Day 44: biopsies. Endomyocardium unremarkable, but taken after heavy glucocorticoid exposure; skeletal muscle dystrophic. Cardiac microdystrophin measured in a human for the first time:
- vector copy number higher in heart than in skeletal muscle
- transcripts skewed towards the 5′ end of the cassette, i.e. incomplete packaging — also demonstrable in the clinical vector lots
- microdystrophin in 5 percent of cardiomyocytes and 10 percent of skeletal fibres, below 1 percent of normal dystrophin on Western blot
- in skeletal muscle the dystrophin–glycoprotein complex was restored in positive fibres; in heart it was not
Such heterogeneity may limit long-term efficacy and could aggravate arrhythmogenic risk.
Sampling at six weeks precedes stable episome formation, so expression may still rise.
The packaging defect will not.
The events were captured by institutional monitoring more extensive than the label recommends, and the authors call for safety monitoring beyond label.
One patient: a larger cohort is needed before generalising.”
Other posts featuring Wolfgang Miesbach on Hemostasis Today.
-
Jul 24, 2026, 08:58Aryabhatta Sadhu: Advancing Patient Blood Management with Rational Transfusion
-
Jul 24, 2026, 08:58Vikash Jaiswal: Toward Better ASCVD Risk Assessment for South Asian Populations
-
Jul 24, 2026, 08:57Muna Adam: Plasma-Derived Factor X Concentrate Used in First UAE Roma Variant Cases
-
Jul 24, 2026, 08:32Cedric Stephane Fosso: Every Drop of Blood Matters – A Child’s Silent Cry for Hemophilia Awareness
-
Jul 24, 2026, 08:19Afila Thasnim EK: Blood Grouping Discrepancies – A Critical Challenge in Transfusion Medicine
-
Jul 24, 2026, 05:15Jade Morrissey: Grateful to Present My PhD Research in Immunothrombosis at ISTH 2026
-
Jul 24, 2026, 05:04Moustafa Abdou: Unmasking Pure Red Cell Aplasia
-
Jul 24, 2026, 04:53Ana Pedrero Gil: The Future of Blood-Derived Therapies
-
Jul 24, 2026, 04:50Marc Wittwer: How We’re Making Hemostasis Diagnostics Faster, Simpler, and More Ergonomic