Enemy turns saviour- HIV used in gene therapy to treat 'bubble boy' disease

A St. Jude doctor Brian Sorrentino pioneered gene therapy using HIV to save patients of bubble boy disease. The study results were published by the New England Journal of Medicine.

In a new study, scientists altered HIV virus in a way that it couldn't cause disease and then used it to deliver a gene to the patient which he lacked. The patients, eight babies with "bubble boy disease" were born without a working germ-fighting system. That increased their susceptibility to every infection as a threat to their lives. Their lacking gene was fixed by a gene therapy made from one of the immune system's worst enemies - HIV, the virus that causes AIDS.

SCID is caused by a genetic flaw that keeps the bone marrow from making effective versions of blood cells that comprise the immune system. It affects 1 in 200,000 newborns, almost exclusively males. Without treatment, it often kills in the first year or two of life.

Allogeneic hematopoietic stem-cell transplantation for X-linked severe combined immunodeficiency (SCID-X1) often fails to reconstitute immunity associated with T cells, B cells, and natural killer (NK) cells when matched sibling donors are unavailable unless high-dose chemotherapy is given. When doctors first tried it 20 years ago, the treatment had unintended effects on other genes, and some patients later developed leukaemia. The new therapy has safeguards to lower that risk.

"This therapy has cured the patients," although it will take more time to see if it's a permanent fix, said Dr Ewelina Mamcarz, one of the study leaders at St. Jude Children's Research Hospital in Memphis.

The nickname "bubble boy disease" comes from a famous case in the 1970s - a Texas boy who lived for 12 years in a protective plastic bubble to isolate him from germs. A bone marrow transplant from a genetically matched sibling can cure SCID, but most people lack a suitable donor. Transplants also are medically risky - the Texas boy died after one.It is now thought that gene therapy could be a solution.

Gene therapy involves removing some of a patient's blood cells, using the modified HIV to insert the missing gene, and returning the cells through an IV. Before getting their cells back, patients are given a drug to destroy some of their marrow so the modified cells have more room to grow.

Within a few months, normal levels of healthy immune system cells developed in seven boys. Previous infections cleared in all infants, and all continued to grow normally. IgM levels normalized in seven of the eight infants, of whom four discontinued intravenous immune globulin supplementation; three of these four infants had a response to vaccines. Vector insertion-site analysis was performed in seven infants and showed polyclonal patterns without clonal dominance in all seven.

A small study of older children suggested it was safe. The new study tried it in infants, and doctors are reporting on the first eight who were treated at St. Jude and at UCSF Benioff Children's Hospital San Francisco.

Within a few months, normal levels of healthy immune system cells developed in seven boys. The eighth needed a second dose of gene therapy but now is well, too. Six to 24 months after treatment, all eight are making all the cell types needed to fight infections, and some have successfully received vaccines to further boost their immunity to disease.

In addition, no serious or lasting side effects occurred. Doctors have not been able to ascertain costing of the procedure but are contemplating to use it in other diseases like sickle cell disease.

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DOI: 10.1056/NEJMoa1815408