Gene replacement therapy shows promise in patients with blood disorder, study finds

Gene replacement therapy once sounded like science fiction, but today it's making its way to mainstream medicine.

Researchers at Lurie Children's Hospital began a study looking at the therapy’s promise four years ago, and it has already yielded some promising results. The international clinical trial tested a new approach to replacing faulty genes in Thalassemia sufferers.

Thalassemia is a genetic blood disorder where patients don’t make enough hemoglobin, which carries oxygen through the body in red blood cells. The cells can be replaced with transfusions, and children with the most severe form of the disease receive blood every three to four weeks for the rest of their lives. But with every transfusion comes an iron load, which builds up in the organs, damaging the liver and the heart. Over time, patients experience organ failure. Life expectancy for those with the disease is in the late 30s and 40s.

One of the first patients in the study, Wanda Sihanath hopes its will give her the chance to travel the world as a biomedical engineer.

“If I have the chance to not be on transfusions, it will give me the opportunity to travel,” Sihanath said.

Instead of donor cells, Wanda’s own stem cells were modified in a lab to carry a healthy copy of the gene, and then returned.

“We take a virus that carries a healthy gene, that gets into patients' stem cells, and starts producing normal proteins,"  explains Dr. Jennifer Schneiderman, a hematologist at Lurie Children's Hospital. "So, it changes how their own stem cells make the red blood cells... from being abnormal thalassemia cells to being normal.”

According to results of the study published Wednesday in the New England Journal of Medicine, 22 patients have undergone the treatment as part of the clinical trial so far. Doctors have been following their progress for about 45 months, and 15 of the patients— including Wanda — are now transfusion-free. The others have reduced their transfusions by 70 percent.

“The vast majority of patients are either transfusion-free, or if they had the genotype where they didn’t produce any normal beta globin gene, they’ve had a significant reduction in transfusion. This is something that could easily open up to many more patients and make their lives a lot better,” Dr. Schneiderman said.

Doctors warn it’s too soon to call the gene replacement therapy a cure, and it’s not without risk. Patients undergo chemotherapy to destroy their existing cells before the new, altered stem cells are infused. So, there’s potential for life-threatening infections, liver and kidney toxicities as well as long-term lung damage. Still, the benefits may outweigh the risks for many patients.