Seeking a cure for ‘bubble boy’ disease

Felsburg

John Donges

Peter Felsburg, the Trustee Professor of Immunology in the School of Veterinary Medicine.

Made famous by the television show “Seinfeld,” the real “bubble boy” was no joke. David Vetter, the boy who lived in a plastic bubble until his death at the age of 12, suffered from a disease known as Severe Combined Immunodeficiency, or SCID.

Peter Felsburg, Trustee Professor of Immunology at Penn’s School of Veterinary Medicine, has been studying the most common form of the disease, X-linked SCID, for more than 25 years. A new funding award of $12 million over the next five years from the National Institutes of Health will enable Felsburg, along with colleagues at the Fred Hutchison Cancer Research Center and several other institutions, to focus on a novel type of gene therapy that might safely treat the condition.

X-linked SCID affects only boys, impacting one of every 30,000 newborns. In these patients, the B and T cells—important players in fighting disease—are low in number and function poorly, rendering babies helpless to infection. Untreated, baby boys often die before the age of 2. Bone marrow transplants can save their lives, but the transplants require a genetically matched donor, usually a sibling. In addition, many newborns contract an infection before the disease is even diagnosed.

Beagle

Penn Vet

A treated beagle two years after receiving an earlier version of a gene therapy treatment.

To better comprehend the underlying cause of the disease and to test possible treatments, Felsburg and colleagues developed a model of X-linked SCID in basset hounds. Studies of these dogs—dubbed “bubble bassets,” although beagles are now the main breed used—have led to a few different approaches to treatment, using bone marrow transplants and various types of gene therapy, where the dogs receive healthy copies of the defective gene. Though other researchers have created a mouse model of XSCID, Felsburg says the immunologic defect in the mice differs from that of the human and dog, and dogs have remained a superior model species for evaluating the efficacy of treatments.

“The dog is the mirror image of what happens in humans with the disease,” he says.

While previous gene therapy trials have advanced to the stage of human clinical trials, problems have emerged. Some patients have developed leukemia. With the new funding, Felsburg and the other researchers will test a new approach, using a type of retrovirus called a foamy virus, to deliver a “good” copy of the SCID-affected gene into patients.

“These foamy virus vectors, because of the way they behave biologically, are proposed to be safer than the previous gene therapy vectors used in human patients,” says Felsburg.

By the end of the five-year project, Felsburg and his research partners hope to have enough data from trials in dogs and mice to win approval for clinical trials of the foamy virus therapy in humans.

Originally published on October 11, 2012