Just when it seemed that a new gene therapy for sickle cell disease was heading towards success, the company that developed the treatment found that two patients now had cancer and stopped testing.
A patient who was treated five and a half years ago has developed myeloidesplastic syndrome, a form of cancer that is often a precursor to leukemia, Bluebird Bio reported, While others have developed acute myeloid leukemia.
It is not clear whether cancers are associated with experimental gene therapy. But sudden trauma is a disappointment for many sickle cell patients, mostly African-Americans, who Had hoped that a cure was on the horizon.
“It seems that the sickle cell disease community just might never get a break,” Dr. Melissa J. Frey-Jones is a researcher at the University of Texas School of Medicine in San Antonio.
“My second concern is that the black community has again lost faith or confidence in research studies because it has taken the medical community to gain some degree of trust for so long,” he said.
It is not yet clear what caused the cancer. One possibility is that inefficient viruses used to deliver gene therapy treatments damaged critical DNA in blood-forming cells in patients’ bone marrow. This would be the worst case, with the head of the Cellular and Molecular Therapeutics Branch at the National Heart, Lung and Blood Institute, Dr. John F. Tisdale stated.
But there is also the possibility that both cancers were caused by a powerful drug, Bussaflan, which is used to cleanse the bone marrow to make room for new cells modified by gene therapy. Dr. Tisdale said bassulfan is known to avoid a blood cancer risk. If it turned out to be the culprit in Bluebird Bio’s trial, “We know what we know.”
Disabled lentaviruses were used with safety features to give Bluebird its gene therapy. It is thought to be much less risky than the virus used in gene therapy years ago, leading to immune deficiency in children. A lentavirus is being used in gene therapy testing for sickle cell disease at Boston Children’s Hospital.
Dr. Tisdale stated that the first patient in Bluebird’s trial developed myeloidplastic syndrome about three years after receiving gene therapy. An examination found that it was caused by busulfan.
The new case is “very similar to what we saw in the first patient” Dr. Tisdale said. At this point, however, more testing simply needs to establish that the new patient actually has the syndrome, he said.
Bluebird is completing an analysis to determine whether the gene inserted into the patients’ DNA landed near the new cancer-associated gene. If not, Busulfan is the likely culprit.
Complicating the question is the fact that people with sickle cell disease are at increased risk of leukemia even without treatment. Nevertheless, no one expects two patients to be screened for the disease.
If gene therapy turns out to be at fault, it is unclear what the Food and Drug Administration will do.
Dr., a hematologist at Boston Children’s Hospital. David A. Williams stated that sickle cell disease itself is degenerative and debilitating, which over time causes intense pain and damage to harmful tissues and organs.
The risk of gene therapy can be offset by the benefits of a treatment that can reduce this terrible burden, he and other experts said.
Director of the Vanderbilt-Mehri-Matthew Walker Center of Excellence in sickle cell disease, Drs. Michael R. Researchers should be careful to speculate about what it would mean for bluebird’s gene therapy, said Debon. But he said he diagnoses cancer as “a cautionary tale between cutting-edge science, clinical trials with few participants and hope for a population that has been largely ignored in the medical community.” . “
He is optimistic, however, that there will be sufficient evidence to eventually make informed choices about curious treatments for patients, including gene therapy and bone marrow transplantation.
“At the end of the day, families want the disease to be treated.” “They can’t join the discussion for a cure, but they want to know that they have a choice.”