Gene Therapy For Sickle Cell Not Linked To Cancer, Bluebird Finds

The biotech company Bluebird Bio intends to resume clinical trials of a sickle cell disease gene therapy that were halted in February after a participant was diagnosed with acute myeloid leukemia five years after treatment. The company released a statement yesterday (March 10) claiming an investigation has found “it is very unlikely” the AML is related to the therapy and the firm is seeking approval from the US Food and Drug Administration (FDA) to resume the trials.

The therapy works by taking a patient’s own hematopoietic stem cells (HCS) and using a lentiviral vector to insert a healthy copy of a β-globin gene. After the patient who had received the gene therapy was diagnosed with AML, Bluebird examined the cancer cells and found the vector DNA incorporated into their genome. Upon additional testing from independent sources, researchers found that the vector landed within the VAMP4 gene and did not seem to have affected the expression or regulation of nearby genes.

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“VAMP4 has no known association with the development of AML nor with processes such as cellular proliferation or genome stability,” Bluebird’s Chief Scientific Officer Philip Gregory says in the press release. Furthermore, the patient’s cells had mutations in other genes, which are related to leukemia.

In early February, a patient from a different arm of the trial was diagnosed with myelodysplastic syndrome (MDS), a condition of malformed blood cells that often precedes AML, although the company has more recently said that the diagnosis is uncertain, Science reports. The same vector is used in an experimental treatment for β-thalassemia and though there haven’t been any cancers in connection with that treatment, those trials were put on hold as well.

“These [preliminary] data indeed point away from the vector as causative,” John Tisdale of the National Heart, Lung and Blood Institute who was not involved in the trial tells The New York Times.

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