Further incidences of insertional mutagenesis related cancer have been identified in patients treated for cerebral adrenoleukodystrophy (ALD).
The FDA had approved a lentivirus mediated gene therapy product for the treatment of ALD, an X-linked disease caused by a mutation in ABCD1. This mutation leads to the build up of fats around nerve cells, interfering with the myelin sheath and reducing the rate of nerve transmission. This disease is often fatal in early life, with other symptoms including seizures and blindness.
The gene therapy product, developed by Bluebird Bio, allowed autologous transplantation of T cells, specifically CD34+ cells, corrected with a lentivirus carrying the complete copy of ABCD1. Unfortunately, 7 of the 67 patients who received the therapy have been shown to develop insertional mutagenesis related cancer.
Integration site analysis found integrations in clones at MECOM-EVI1 or PRDM16, with multiple other somatic mutations. The results have been published recently in the New England Journal of Medicine.
The need to understand vector safety with regards to genotoxicity is paramount and at TestAVec, we aim to derisk these gene therapies by understanding genotoxicity vectors at an early stage.
Komentarze