Hemostasis Today
NewsFeed
Headlines Hematology Health Medicine VTE ASH Plasma Donation
February, 2026
February 2026
M T W T F S S
 1
2345678
9101112131415
16171819202122
232425262728  
Wolfgang Miesbach on The 1st Case of Secondary Malignancy Triggered by Integrated AAV
Wolfgang Miesbach/LinkedIn
Feb 1, 2026, 11:50

Wolfgang Miesbach on The 1st Case of Secondary Malignancy Triggered by Integrated AAV

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

”Is there evidence that integrated AAV can trigger oncogenesis in a clinical setting?

First case worldwide with molecular evidence linking AAV integration to human malignancy.

The FDA placed clinical holds on REGENXBIO’s AAV9-based gene therapies after detecting a CNS tumour in a 5-year-old with Hurler syndrome (MPS I).

The case:
Patient: 5-year-old with Hurler syndrome (MPS I)
Therapy: RGX-111 — AAV9 carrying IDUA gene (α-L-iduronidase)
Dose: 5.0×10¹⁰ vg/gram brain mass (~10¹³⁻¹⁴ total)
Route: Intracisternal injection (direct CSF)
Timeline: Brain tumour detected 4 years post-injection
Status: Asymptomatic; surgically resected; progressing developmentally

Critical context: No tumours in 9 other RGX-111 recipients or 32 RGX-121-treated patients (some followed ~7 years).

Pathogenic mechanism:

Finding: AAV integration in resected tumour with PLAG1 proto-oncogene overexpression.
Mechanism: PLAG1 (pleomorphic adenoma gene 1) is normally silenced in adult tissues. AAV integration may have created a promoter substitution event—placing the strong CMV/CB7 promoter near PLAG1, driving ectopic overexpression. This recapitulates the exact mechanism in spontaneous PLAG1-driven tumours (salivary adenomas, lipoblastomas).

Context: At clinical doses (~10¹⁴ vector genomes), even 0.1–1% integration frequency equals millions of integration events per patient.

Implications for haemophilia gene therapy:

Haemophilia therapies target the liver (AAV5/AAV8), not CNS (AAV9)—fundamentally different biology.
Evidence from >500 haemophilia patients treated with gene therapy:
8 cancer cases reported total: NO evidence AAV caused the cancer—
Adult hepatocytes are postmitotic; strong regenerative capacity dilutes integrated genomes
AAV5/AAV8 are liver-selective; minimal CNS penetration

This case increases uncertainty and awareness. Patient awareness and informed consent so importannt:

  • Detailed baseline information before treatment
  • Explicit shared decision-making
  • Long-term surveillance protocols and registries”

Read the full announcement here.

Wolfgang Miesbach on The 1st Case of Secondary Malignancy Triggered by Integrated AAV

Stay updated with Hemostasis Today.

AAV cancer CNS tumours FDA Gene therapy Health Hematology Hemostasis Hemostasis News Hemostasis Today Medicine OncoDaily PLAG1 REGENXBIO Wolfgang Miesbach
NewsFeed