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.
-
Sep 17, 2026, 10:08WFH 2027 Comprehensive Care Summit Opens Abstract Submissions – World Federation of Hemophilia
-
Sep 17, 2026, 09:56Marianne Yee: MySCDstory Expands Access to Multilingual Sickle Cell Education
-
Sep 17, 2026, 09:36Enewa Onoja: Platelet Satellitism Phenomenon, Three Misleading Counts
-
Sep 17, 2026, 09:22Emmanuel J Favaloro: Hemostasis and Thrombosis in Exercise and Athletes
-
Sep 17, 2026, 09:18Updated Iron Deficiency Diagnostic Guidelines – American Society of Hematology
-
Sep 17, 2026, 09:14Angela Weyand: ASH 2026 Iron Deficiency Guidelines
-
Sep 17, 2026, 08:18Anirban Sen Gupta: From Flow to Clot Insights Into Hemostasis and Thrombosis
-
Sep 17, 2026, 08:03Aya Sherif: HEMO COP – Building a Collaborative Future for Hemophilia Care
-
Sep 17, 2026, 07:50Applications Are Now Open for the 2026 WFH IHTC Fellowships