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For years, an experimental gene treatment has been able to reverse sickle cell disease

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A multicenter research demonstrated that an experimental gene therapy for sickle cell disease restored blood cells to their proper form and removed acute pain crises for years following treatment.

In some patients, a single dosage of an experimental gene treatment for sickle cell disease returned blood cells to their normal form and eradicated the illness’s most dangerous consequence for at least three years, according to a research.

The multicenter trial, the first to report on such long-term effects of a sickle cell gene therapy, included four patients from NewYork-Presbyterian/Columbia University Irving Medical Center. The research was published online December 12 in the New England Journal of Medicine, with corresponding author John F. Tisdale, MD, a senior investigator at the National Heart, Lung, and Blood Institute of the National Institutes of Health.

The single-dose therapy, which was tested on 35 adults and adolescents with sickle cell disease, not only effectively corrected the shape of the patients’ red blood cells, but it also completely eliminated episodes of severe pain caused by rigid, crescent-shaped red blood cells clumping together and obstructing blood vessels. The excruciating bouts often cause extensive organ damage. These incidents are a leading cause of emergency room visits and hospitalizations, as well as early mortality.

“The potential effect of this novel treatment cannot be overstated,” said Markus Y. Mapara, MD, PhD, a co-author of the research and a professor of medicine at Columbia University’s Vagelos College of Physicians and Surgeons. “People with sickle cell disease are always on the lookout for the next pain flare-up. This medicine may be able to help patients with this condition reclaim their lives. We hope that this treatment can be helpful in younger kids as well, so that they may grow up pain-free and live longer.”

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Mutations in the beta-globin gene cause sickle cell disease, which results in the production of defective hemoglobin, the oxygen-carrying protein in red blood cells. Normal red blood cells are shaped like donuts, but sickle cell disease causes red blood cells to stiffen and take on a spiky, sickle-like appearance due to aberrant hemoglobin. The illness is expected to impact 100,000 persons in the United States, with Black Americans being the most affected. Sickle cell disease may be healed with a donor bone marrow transplant, however this treatment works best in people who have a closely matched sibling donor, which is a small percentage of the population. Patients with sickle cell disease have a median lifetime of 40 years.

LentiGlobin is a revolutionary gene treatment that collects blood-forming stem cells from the patient’s blood. The stem cells are subsequently infected with harmless lentiviruses that transmit a modified copy of the beta-globin gene. After being reinfused into the patient, the cells settle in the bone marrow and begin producing healthy new red blood cells.

The treatment entirely eradicated acute pain crises in the months after infusion (follow-up varied from 4 to 38 months) in the clinical study, which is the longest amount of time that a gene therapy for sickle cell disease has been evaluated.

“The benefits have been maintained throughout the trial time, indicating that the outcomes may be long-lasting,” adds Mapara, who is also the head of the NewYork-Presbyterian/Columbia University Irving Medical Center’s Bone Marrow Transplantation and Cell Therapy Program.

Because LentiGlobin utilizes a patient’s own stem cells, there is no chance of rejection, which is a typical side effect of traditional bone marrow transplants, according to Mapara.

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One drawback of gene therapy is that patients must first undergo conditioning, which involves high-dose chemotherapy to destroy old stem cells and create place for the modified stem cells. Chemotherapy has the potential to be harmful and is linked to a tiny risk of cancer. Two individuals in the experiment got leukemia, which the researchers believe was caused by the chemotherapy rather than the LentiGlobin.

Researchers are presently developing less harmful methods of training bone marrow prior to gene therapy. “The ultimate objective will be to deliver this medication as soon as feasible,” Mapara adds, “far before individuals acquire organ damage and other sickle cell disease consequences.” “However, we need to develop a safer alternative to chemotherapy for conditioning tactics like antibodies before we can achieve that.”

The NewYork-Presbyterian/Columbia University Irving Medical Center is one of the few facilities in the world that is participating in sickle cell disease gene therapy clinical studies. In addition, Columbia University researchers want to find ways to make gene therapy for sickle cell disease more affordable.

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