More than two years after receiving a gene therapy treatment intended to restore immune functioning, 48 kids with severe combined immunodeficiency are healthy, according to a study published yesterday (May 11) in The New England Journal of Medicine.
“We’re taking what otherwise would have been a fatal disease,” and largely fixing the problem, study coauthor Donald Kohn of Mattel Children’s Hospital at the University of California, Los Angeles, tells the Associated Press. Now, he adds, “[t]hey’re basically ‘free range’—going to school, doing normal things,” without fear of a life-threatening infection.
“People ask us, is it a cure? Who knows long term, but at least up to three years, these children are doing well,” Stephen Gottschalk of St. Jude Children’s Research Hospital in Memphis who was not involved in the study but has tested a similar gene therapy, tells the AP. “The immune function seems stable over time so I think it looks very, very encouraging.”
The most common form of severe combined immunodeficiency syndrome (SCID), also known as bubble boy or bubble baby disease, results from genetic mutations in the ADA gene that encodes an enzyme called adenosine deaminase that is involved in immune function. These mutations prevent proper immune development and usually kills patients within one to two years of life. Bone marrow transplants have been used to treat the disorder, but suitable donors are not always available and the procedure carries risks. Twice-weekly doses of antibiotics and antibodies are often used as a stop-gap measure, but gene therapies promise to fix the root of the problem.
Three independent Phase 1/2 trials, two in the US and one in the UK, tested a gene therapy in 50 babies and toddlers with SCID due to mutations in ADA (ADA-SCID). The researchers removed blood cells from the patients and used a modified lentivirus to deliver a healthy version of ADA before infusing the cells back into the children. Two to three years later, 48 of the patients have immune systems that can effectively fight invading pathogens, including COVID-19.
“These findings suggest that this experimental gene therapy could serve as a potential treatment option for infants and older children with ADA-SCID,” Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, says in a press release. “Importantly, gene therapy is a one-time procedure that offers patients the hope of developing a completely functional immune system and the chance to live a full, healthy life.”
The other two children, who did not respond to the gene therapy, have both received successful bone marrow transplants.