Gene therapy breakthrough ends lifelong transfusions

Jorge and Jullisa
Living with the inherited blood disorder beta-thalassemia is a challenge. Those with the most severe type, beta-thalassemia major, require life-long blood transfusions and careful medical monitoring to survive. Untreated, the spleen, liver and heart become enlarged, bones become deformed and growth is inhibited. About 40,000 babies are born with beta-thalassemia each year worldwide.
It takes fortitude to endure a lifetime of regular blood transfusions and medication to rid the body of excess iron caused by transfusions. “I’m in awe of the courage of these patients,” says Alexis Thompson, MD, PhD, Director of the Comprehensive Thalassemia Program at Ann & Robert H. Lurie Children’s Hospital of Chicago and Professor of Pediatrics at Northwestern University Feinberg School of Medicine.
This same strength has led several of Dr. Thompson’s patients to participate in a groundbreaking international multicenter clinical trial with results that Dr. Thompson says are “stunning.” Dr. Thompson is the lead investigator of a gene therapy study called the Northstar Study, sponsored by bluebird bio, which uses the patient’s own stem cells to replace the gene that is defective in thalassemia. If successful, gene therapy for thalassemia will restore the ability of patients to make the protein inside red blood cells called globin that is needed to carry oxygen.
Since March 2014, all patients in the study have successfully engrafted following their transplant, meaning the infused stem cells started to grow and make new blood cells. The patients range in age from 18 to 35 years. To date, all of the Lurie Children’s patients are now transfusion-free.
“If she can do it, I can do it”
Lurie Children’s is home to the largest thalassemia treatment center in the Midwest and has cared for Julissa Perez, 18, and her brother Jorge Perez Jr., 7, since infancy. Julissa underwent gene therapy in November 2014 and two months later fulfilled a dream by enrolling in the nursing program at St. Xavier University in Chicago.
Julissa’s mother, Guadalupe, says that she has been hoping for a cure since her daughter’s diagnosis as an infant. Unsuspected by Guadalupe and husband Jorge Sr., they both carried the gene for thalassemia. “My whole world fell in,” Guadalupe says now. “I didn’t know if I could handle it. Then I began to read everything I could find about thalassemia.”
When Guadalupe read about the Northstar Study, she encouraged Julissa to consider participating. Though Julissa has experienced serious health problems from thalassemia, including bone deformities, removal of an enlarged spleen, and fatigue, she has tolerated blood transfusions well. She was curious about the new therapy, however, and discussed its pros and cons with her doctors. She was also able to talk with 19-year-old Wandasun Sihanath, the first patient to undergo the gene therapy at Lurie Children’s, in April 2014. Julissa decided to take the plunge. “I thought ‘if she can do it, I can do it,’” she says now.
Seeing sick cells turn healthy
Living with thalassemia was good preparation for the rigors of gene therapy. Julissa went on medication to mobilize her stem cells, which were collected at Lurie Children’s. In the lab, her stem cells were then treated with a modified virus to introduce the healthy human globin gene into her stem cells. Once tests determined that Julissa’s cells were expressing the new gene, she was admitted to the hospital for chemotherapy to prepare her body for the new cells.
After the cell infusion, Julissa was kept in isolation at the hospital for another three weeks, seeing only immediate family. She was discharged when doctors saw early evidence that her cells were making normal adult hemoglobin. “We are particularly pleased,” Dr. Thompson says, “at how early and robust the expression of the new gene is and how tolerable the side effects are for patients.”
Julissa and her fellow study participants will be monitored for many years to determine whether the new gene continues to work efficiently over time. “We are not yet using the term ‘cure,’” Dr. Thompson says. Patients also are being monitored for any signs of cancer or late effects, as the process of modifying stem cells carries a slight risk of altering DNA in a way that can lead to cancer.
Seeing hope for her son
If the Northstar Study continues to go well, Dr. Thompson envisions opening the trial up to younger children and also starting a separate trial for patients with sickle cell disease, another blood disorder that is caused by a single mutation in the globin gene. “This has been such a rewarding journey,” Dr. Thompson says. “The success of this trial to date is a tribute to the vision of Lurie Children’s leadership, the work of the entire thalassemia and stem cell
transplant teams, and the willingness of the patients and their families to embrace new technology and advocate for themselves.”
Julissa’s mother is closely following the results of the Northstar Study in hopes that Jorge may be able to participate in the future. “I would be thrilled if Jorge could also benefit like Julissa,” she said. “I want both my children to be able to look forward to healthy futures where they can accomplish their dreams.“
Alexis Thompson, MD, PhD, is the A. Watson and Sarah Armour Professor in Childhood Cancer and Blood Diseases.
This article originally appeared in the Spring 2015 issue of Heroes magazine.