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A healthy copy of the affected gene is introduced into the patient's stem cells by means of a gene delivery vehicle called a vector, a genetically altered virus that can penetrate cells but does not cause ongoing infection. The process begins by isolating blood stem cells from the patient's bone marrow. The therapeutic gene, inserted into the vector's genome, is then delivered into the patient's stem cells. The patient's stem cells, now corrected for the defect, are infused back into the patient in the clinic. |
Gene therapy holds the promise to cure a variety of diseases caused by single-gene mutations. But clinical trials stalled after the death of a patient in a trial at the University of Pennsylvania, and after five boys with SCID-X1, a severe X-linked immune deficiency disease, developed leukemia as a result of their treatment in Europe. Now, an international clinical trial has cleared all regulatory hurdles and is recruiting patients, reviving this potentially life-saving treatment.
The first gene-therapy trial for SCID-X1 to be approved by the FDA is sponsored in the U.S. by Children's Hospital Boston's David A. Williams, MD, chief of Hematology/Oncology and director of Translational Research. It will use a completely redesigned gene-delivery vector, expected to be much safer. The Children's-Dana Farber Cancer Institute team, which also includes Luigi Notarangelo, MD, (Immunology) and Sung-Yun Pai, MD, (Hematology/Oncology) has been awarded a five-year, $4.7 million grant from the National Institute of Allergy and Infectious Diseases to support the trial's implementation. "The many years of research investment and development are now paying off," says Dr. Williams.
The five participating centers in the United States and Europe will enroll a total of 20 children with SCID-X1. Patients will be infused with stem cells from their own bone marrow, in which the normal counterpart of the defective gene has been introduced. Patients will have their immune function assessed at six months, and will be monitored for 15 years to detect any possible cancers.
Gene therapy may provide a safer alternative for patients who otherwise would have to undergo bone marrow transplant, the only curative treatment. If this trial succeeds, it should pave the way for treating several other single-gene diseases with gene therapy. A second multicenter trial, for Wiskott-Aldrich syndrome, a primary immunodeficiency disease affecting platelets, is now undergoing regulatory review. Children's would be the sole U.S. site, and enrollment is hoped to begin in late 2010 or early 2011.
More information: For information on enrolling in the SCID-X1 trial: ClinicalTrials.gov,
or contact dawilliams@childrens.harvard.edu, Luigi.Notarangelo@childrens.harvard.edu or Sung-Yun.Pai@childrens.harvard.edu.
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