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Penn investigates gene therapy as a new way of treating immune deficiencies

July 1, 2006
Jessica Tremayne

Philadelphia - A corrective gene is being injected into the bloodstream of immune deficient dogs to correct hematopoietic stem cells at the University of Pennsylvania.

PHILADELPHIA — A corrective gene is being injected into the bloodstream of immune deficient dogs to correct hematopoietic stem cells at the University of Pennsylvania.

Severe Combined Immunodeficiency Disorder of the X chromosome (XSCID) affects males and has been treated with bone marrow transplants in the past.

However, this method has proven to have severe side effects. In a French study conducted on human boys with XSCID, 10 boys developed normal immune systems after receiving the treatment, but three of the boys developed T-cell leukemia as a side effect.

Dogs in the study were directly injected with the vector, transferring a corrective gene into the bloodstream, says Dr. Suk See Ting-De Ravin, a National Institute of Allergy and Infectious Disease (NIAID) researcher on the project.

"The new process restored immune function in three of the four dogs tested," Suk See Ting-De Ravin says.

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Researchers used Basset Hound puppies that had XSCID, separating them into long-term and short-term groups. The oldest dog participating in this study is now 2 years old, says Dr. Peter Felsburg, professor of immunology at Penn's School of Veterinary Medicine and lead researcher in the study.

Eighteen months after the treatment was given, the dogs in the long-term study appear to be cured of the XSCID with no side effects, he says.

This study shows a potential treatment for XSCID patients both canine and human, Felsburg adds.

"Study results show that this therapy is more effective long term than other methods that haven't proven to have generated new immune cells," he says.

The human study took bone marrow cells out of affected boys then exposed the cells to a retroviral vector containing the normal gene cultured in vitro and transplanted the cells back into the patient.

"This new method was necessary to help humans and maybe dogs," Felsburg says. "It can extend quality of life for XSCID patients and possibly those with other immunologic diseases.

There is not a high reporting of these cases in dogs, so it is hard to tell how common the defect occurs. However, it occurs in about 1 in 100,000 human births, so we can conclude it happens more often in dogs because of the way we breed them, Felsburg says.

"Untreated dogs die between 10 and 14 weeks after birth and have a 50/50 chance of contracting the faulty gene from their mother," he adds.

Felsburg has been conducting the gene-therapy study for three years.

"It is amazing that the dogs that underwent this therapy are absolutely normal immunologically," Felsburg says. "Unfortunately I don't know how practical this treatment will be for veterinarians to apply. Male dogs treated and cured with this technique can still carry the faulty X chromosome gene to their offspring."

Study findings were published in the April 15 journal Blood.

Research was funded by the National Institutes of Allergy and Infectious Diseases and the National Institutes of Health.


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