Nearly 50 infants with “bubble baby” disease developed a working immune system after they received a gene therapy that contained the AIDS virus, according to a new study.
Nearly 50 infants with “bubble baby” disease, or X-linked severe combined immunodeficiency (SCID-X1), developed a working immune system after they received a gene therapy that contained the AIDS virus, according to study results reported Tuesday.
SCID-X1 is an inherited disorder that affects the immune system and occurs nearly exclusively in boys. Infants with the condition face a high risk of recurrent and persistent infections due to a lack of immune cells needed to fight off viruses and bacteria.
Doctors typically use a bone marrow transplant to treat SCID-X1 early on in life before infections occur. Transplants are usually performed within the first three months as this window is generally associated with a higher success rate. Transplants can be lifesaving, but to date, they only partially restore the baby’s immunity.
A research team at Saint Jude Children’s Research Hospital in Memphis has developed a potentially curative investigational gene therapy using harvested bone marrow stem cells from a child with the disorder. The researchers inserted the normal gene missing in these patients into the cells. The therapy was then infused back into the affected infants, causing cells to populate and revive and restore immunity.
A surprising vector in the therapy is an engineered copy of HIV, the virus responsible for AIDS. Although seemingly alarming, patients who receive the treatment can’t get infected with HIV, according to study author Dr. Morton Cowan of the University of California, San Francisco. “It originated as HIV, but it’s really no longer HIV when it’s inserted,” he said in an interview with CNN.
Co-author Dr. Stephen Gottschalk, chair of the Department of Bone Marrow Transplantation & Cellular Therapy at St. Jude Children’s Research Hospital, said the "[HIV] virus is able to effectively deliver the healthy copy of the gene into the stem cells in a way that was not possible before,” making it “safer and more effective for gene therapy.”
Findings from the study were published in the New England Journal of Medicine. Results show the overall survival was 100% up to 24 and 36 months. Additionally, event-free survival (EFS) was 97% in the U.S. and 100% in UK cases at 12 months. At 36 months, the EFS rate was 95% in UK babies.
Additionally, 90% of patients in the U.S. and 100% of patients in the UK discontinued immunoglobulin replacement therapy by 24 and 36 months, respectively, demonstrating robust immune reconstitution. There was no evidence of monoclonal expansion, leukoproliferative complications, or replication-competent lentivirus emergence. Adverse events associated with the therapy were considered low grade in their severity.
A total of 48 babies and toddlers from the U.S. and the UK born without a working immune system experience restoration of their immune system with the treatment, while two did not. The two out of 50 children who did not benefit from the gene therapy later underwent bone marrow transplants. The researcher notes that longer-term follow-up is needed to determine if any of the 50 participants in the study were cured, but they say the children seem to be doing well currently.
