Children's Researchers Find Promise in New Gene Therapy Treatment

Seattle, Wash.: Researchers at Children's Hospital and Regional Medical Center in Seattle and the University of Washington School of Medicine have identified a way to replace a mutated gene in mice with X-Linked Agammaglobulinemia (XLA), an inherited primary immune deficiency disease.


Seattle, Wash.: Researchers at Children's Hospital and Regional Medical Center in Seattle and the University of Washington School of Medicine have identified a way to replace a mutated gene in mice with X-Linked Agammaglobulinemia (XLA), an inherited primary immune deficiency disease.

The study, published in Blood, the Journal of the American Society of Hematology, found that a retroviral gene therapy could successfully rescue immune cell development and promote the generation of antibodies in mice that lacked antibody-producing cells.

"There are more than 130 different types of primary immune deficiency diseases identified to date, each caused by different genetic defects. Because many of these lead to a lack of infection-fighting antibodies, these findings could have a significant impact on finding a cure for a number of these diseases," said Carl Anthony Blau, M.D., associate professor, Division of Hematology at the University of Washington.

More than 500,000 people in the U.S. and 10 million people worldwide are afflicted with a form of primary immune deficiency disease.

XLA, a primary immune deficiency disease affecting only males, leaves patients without the ability to produce antibodies, proteins that make up the gamma globulin in blood plasma. Due to a lack of antibodies, patients with XLA are prone to developing life threatening infections that range from pneumonia to gastrointestinal tract infections and infections of the joints, bones or brain. Currently, patients with XLA receive lifelong monthly transfusions of blood plasma to provide some of the antibodies they lack.

Since XLA is a genetic disease, researchers have been looking for a way to repair or replace the gene. Using a retrovirus to enter cells and deposit a copy of the gene into the cell's chromosome, researchers at UW and Children's were able to rescue the defect in the development of B cells and promote the generation of antibodies.

"We've proven that gene therapy can overcome the disease in mice, now we hope to take what we've learned from this study and apply it to patients suffering from XLA," said David Rawlings, M.D., Head of Children's Section of Immunology and associate professor of Pediatrics and Immunology at the University of Washington School of Medicine. "This supports our pursuing further studies with the goal of conducting clinical trials in the relatively near future."

"Dr. Rawlings' study clearly demonstrates the potential therapeutic benefit of gene therapy for XLA and provides a strong conceptual basis for moving toward a clinical gene therapy trial in this form of immunodeficiency," said Blau.

Rawlings and fellow researchers first identified the gene that causes XLA in 1993. Since then, they have continued to search for a way to restore the normal gene in animal models of XLA and thereby rescue the production of antibodies.

Children's is the leading referral center for children and adults with immune problems in the Pacific Northwest, offering advanced genetic testing capabilities and serving as an international center for prenatal and neonatal testing, and for testing of adults to identify carriers of immune deficiency disorders.

The first edition of the study is available online here and will be printed in the September 2004 edition of Blood.

About Seattle Children’s

Seattle Children’s Hospital, Foundation and Research Institute together deliver superior patient care, advance new discoveries and treatments through pediatric research, and raise funds to create better futures for patients. Consistently ranked as one of the top 10 children’s hospitals in the country by U.S. News & World Report, Seattle Children’s Hospital specializes in meeting the unique physical, emotional and developmental needs of children from infancy through young adulthood. Through the collaboration of physicians in nearly 60 pediatric subspecialties, Seattle Children’s Hospital provides inpatient, outpatient, diagnostic, surgical, rehabilitative, behavioral, and emergency and outreach services to families from around the world.

Located in downtown Seattle’s biotech corridor, Seattle Children’s Research Institute is pushing the boundaries of medical research to find cures for pediatric diseases and improve outcomes for children all over the world. Internationally recognized investigators and staff at the research institute are advancing new discoveries in cancer, genetics, immunology, pathology, infectious disease, injury prevention, bioethics and much more.

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