New Gene Therapy for “Bubble Boy” Disease Appears to be Safe, Effective

PHILADELPHIA A new form ofgene therapyfor boys with X-linked severe combined immunodeficiency syndrome (SCID-X1), a life-threatening condition also known as bubble boy disease, appears to be both effective and safe, according to an international clinical trial with sites inBoston, Cincinnati, Los Angeles, London, and Paris.

Early data published in theNew England Journal of Medicinesuggests that the therapy may avoid the late-developing leukemiaseen in a quarter of SCID-X1 patients in previous gene-therapy trials in Europe that took place more than a decade ago. Left untreated, boys with SCID-X1 usually die of infection before their first birthday.

The lab of coauthorFrederic Bushman, PhD, professor of Microbiology, from thePerelman School of Medicine at the University of Pennsylvania, carried out the deep DNA sequencing on patient specimens to track and verify distributions of integration sites of the vector.The vector used in the new trial was engineered to remove molecular signals implicated in cancers in the first trial.

Eight of nine boys recruited to date to the present trial are alive between 12 and 38 months after treatment, with no SCID-X1-associated infections. The gene therapy alone generated functioning immune systems in seven of eight boys. Genetic studies showed that the new viral vector did not lead to vector insertions near known cancer-causing genes, raising cautious hopes about the vector's long-term safety.

We showed that fewer cells accumulated with integration sites near cancer genes in the second trial, suggesting that the adverse properties had indeed been engineered out, explains Bushman So far there are no clinical adverse events in the present trial -- the integration site data has suggested improved safety.

The modified vector created for the current trial is a self-inactivating gammaretrovirus, designed to deliver its payload effectively while minimizing the chance of inadvertently turning on oncogenes that could lead to leukemia.

The core question of the trial was whether the new self-inactivating viral vector could safely and successfully shuttle a gene called theIL-2 receptor gamma(IL2RG) subunit into the patients' hematopoietic stem cells. In boys born with SCID-X1, mutations render theIL2RGgene inactive, robbing the children of the ability to produce a functional immune system.

For more information, see theDana-Farber/Boston Children's Cancer and Blood Disorders Centersnews release.

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Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of theRaymond and Ruth Perelman School of Medicine at the University of Pennsylvania(founded in 1765 as the nation's first medical school) and theUniversity of Pennsylvania Health System, which together form a $4.3 billion enterprise.

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New Gene Therapy for "Bubble Boy" Disease Appears to be Safe, Effective