Doctors use HIV in gene therapy to fix ‘bubble boy’ disease

Doctors use HIV in gene therapy to fix ‘bubble boy’ disease

Doctors use HIV in gene therapy to fix ‘bubble boy’ disease

United States scientists say they used HIV to make a gene remedy that cured eight infants of extremely mixed immunodeficiency, or "bubble boy" illness. 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. The latest advance, reported in theNew England Journal of Medicine on Wednesday, details a study of eight infants who have a type of SCID called SCID-X1.

Dr Ewelina Mamcarz, from the St June Department of Bone Marrow Transplantation and Cellular Therapy, said: "These patients are toddlers now, who are responding to vaccinations and have immune systems to make all immune cells they need for protection from infections as they explore the world and lead normal lives".

This form of the disease, SCID-X1, first made headlines in the 1970s and 80s with David Vetter - the original "bubble boy" - who spent 12 years in strict isolation to protect himself from infections.

Doctors used gene therapy to cure babies who were born with Severe Combined Immunodeficiency (SCID), a rare and life-threatening disease marked by little or no immune system. "If left untreated, patients rarely live past their second birthday".

Ten infants have received the experimental therapy.

Rights to it have been licensed by St. Jude to Mustang Bio. He is the senior author and died after the manuscript was submitted for publication.

Currently, the best treatment for SCID-XI is a bone marrow transplant with a tissue-matched sibling donor.

Their bone marrow was collected and processed at a central facility to enrich for stem cells that were then transfected with the lentivirus for gene therapy.

X-SCID is caused by a mutation in a gene, IL2RG, which produces a protein essential for normal immune function. But more than 80 percent of SCID-X1 patients lack such donors. "They must rely on stem cells from other donors". That prepared them to rebuild healthy ones from corrected copies of the mutated gene that caused X-SCID, which the researchers inserted into the babies' blood-forming stem cells using an inactive virus.

It worked by scientists creating the gene required to fix sick patients' DNA in a lab, then injecting it into their bodies inside weakened HIV viruses.

One patient treated with the new technique has been followed for more than two and a half years with no sign that the benefits are fading. This helped the new cells take up permanent residence. In these earlier studies, gene therapy restored T cell function but did not fully restore the function of other key immune cells, including B cells and NK cells. All are developing and growing normally.

The researchers now hope the treatment will provide a template to develop gene therapies for other blood and genetic disorders.

However, these patients will need to be tracked to make sure side effects don't crop up, Boyle added.

The babies will, however, be studied to check if the results of the gene therapy last. Lentiviral gene therapy with low dose busulfan for infants with X-SCID.

For example, instead of inserting a healthy gene into blood cells, Porteus, the Stanford pediatrician, has used a precision gene-editing technique called CRISPR to correct the genetic error in blood cells drawn from SCID patients.

The vector includes insulators to block activation of genes adjacent to where IL2RG is inserted into patients' DNA. Both are important steps for expanding access to treatment and commercializing production. Without treatment, it often kills in the first year or two of life.

Dr Mamcarz said the current therapy, which is also being trialled among older SCID-XI patients whose bone marrow transplants had been unsuccessful, was able to deliver gene-corrected cells to a patient in a way not possible before.

Reference: E Mamcarz et al.

The study was supported by the American Lebanese Syrian Associated Charities; by grants from the California Institute of Regenerative Medicine, the National Heart, Lung, and Blood Institute, the National Cancer Institute, the intramural program of the National Institute of Allergy and Infectious Diseases; and by the Assisi Foundation of Memphis.

(Peter Barta/St. Jude Children's Research Hospital via AP) Gael Jesus Pino Alva, 2, plays with toys at a hospital in Memphis.

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