Gene therapy cures form of 'bubble boy disease'By MALCOLM RITTER, AP Science Writer Malcolm Ritter, Ap Science Writer Wed Jan 28, 5:02 pm ETNEW YORK – Gene therapy seems to have cured eight of 10 children who had potentially fatal "bubble boy disease," according to a study that followed their progress for about four years after treatment. The eight patients were no longer on medication for the rare disease, which cripples the body's defenses against infection. The successful treatment is reported in Thursday's issue of the New England Journal of Medicine and offers hope for treating other diseases with a gene therapy approach.Bubble boy disease is formally called severe combined immunodeficiency, or SCID. This genetic disorder is diagnosed in about 40 to 100 babies each year in the United States. The nickname comes from the experience of a Houston boy, David Vetter, who became famous for living behind plastic barriers to protect him from germs. He died in 1984 at age 12.He had the most common form of SCID. Recent studies found that gene therapy produced impressive results for that form of the disease, but also carried a risk of leukemia.The new study involved a different, less common form of SCID — and one that holds a key position in medical history. In 1990 it became the first illness to be treated by gene therapy, according to the U.S. government. Two Ohio girls improved but continued to take medication.This form of SCID arises in babies with a genetic defect that leaves them deficient of an enzyme called adenosine deaminase. Patients can be treated with twice-weekly shots of the enzyme or a bone marrow transplant, but the medicine is expensive and marrow transplants don't always work.Gene therapy for the new study was performed in Italy and Israel. Researchers removed marrow cells from the patients, equipped the cells with working copies of the gene for the enzyme, and injected the cells back into the patients. In most cases, that was done before age 2.The journal article reports the outcome two to eight years later, with an average of four years. All 10 patients were still alive, but two needed further treatment. None showed signs of leukemia or other health problems from the therapy, the researchers said.Dr. Donald Kohn, a SCID expert at Childrens Hospital Los Angeles and the University of Southern California, said scientists are trying to understand why gene therapy produces a leukemia risk with the most common form of SCID but not the enzyme-related form.The new findings are good news for the idea of using gene therapy to treat some other blood cell disorders, including sickle cell disease, said Kohn, who didn't participate in the new study.___On the Net:New England Journal of Medicine: http://www.nejm.orgInformation on SCID: http://www.genome.gov/13014325
CHALLENGES IN GENE THERAPYGene therapy is not a new field; it has been evolving for decades. Despite the best efforts of researchers around the world, however, gene therapy has seen only limited success. Why?The answer is that gene therapy poses one of the greatest technical challenges in modern medicine. It is very hard to introduce new genes into cells of the body. Let's look at some of the main technical issues in gene therapy.Gene delivery and activationGene therapy will work only if we can deliver a normal gene to a large number of cells - say, several million - in a tissue. And they have to be the correct cells, in the correct tissue. Once the gene reaches its destination, it must be activated, or turned on to produce the protein encoded by the gene. Gene delivery and activation are the biggest obstacles facing gene therapy researchers. Tools of the Trade highlights some of the most common methods for addressing these challenges.Introducing changes into the germlineTargeting a gene to the correct cells is crucial to the success of any gene therapy treatment. Just as important, though, is making sure that the gene is not incorporated into the wrong cells. Delivering a gene to the wrong tissue would be inefficient and could cause health problems for the patient.For example, improper targeting could incorporate the therapeutic gene into a patient's germline, or reproductive cells, which ultimately produce sperm and eggs. Should this happen, the patient would pass the introduced gene on to his or her offspring. The consequences would vary, depending on the type of gene introduced.Immune responseOur immune systems are very good at fighting off intruders such as bacteria, viruses and Jesse Gelsinger other biological substances. Gene delivery vectors must be able to escape the body's natural surveillance systems. Failure to do so can cause serious illness or even death.The story of Jesse Gelsinger illustrates this challenge well. Gelsinger, who had a rare liver disorder, participated in a 1999 gene therapy trial at the University of Pennsylvania. He died of complications from an inflammatory response shortly after receiving a dose of experimental adenovirus vector. His death halted all gene therapy trials in the United States for a time, sparking a much-needed discussion on how best to regulate experimental trials and report health problems in volunteer patients.Disrupting important genes in target cellsThe best gene therapy David Vetter is the one that lasts. Ideally, we would want a gene that is introduced into a group of cells to remain there and continue working.For this to happen, the newly introduced gene must become a permanent part of each cell's genome, usually by integrating, or "stitching" itself, into the cell's existing DNA. But what happens if the gene stitches itself into an inappropriate location, disrupting another gene?This happened recently in a gene therapy trial to treat several children with X-linked Severe Combined Immune Deficiency (SCID). People with this disorder have virtually no immune protection against bacteria and viruses. To escape infections and illnesses, they must live in a completely germ-free environment.In the late 1990s, Ryes Evans researchers tested a gene therapy treatment that would restore the function of a crucial gene, gamma c, to cells of the immune system. This treatment appeared very successful, restoring immune function to most of the children who received it.But later, two of these children developed leukemia. Researchers found that the leukemia occurred because the newly transferred gamma c gene had stitched itself into the wrong place, interrupting the function of a gene that normally helps regulate the rate at which cells divide. As a result, the cells began to divide out of control, causing the blood cancer leukemia.Although doctors have treated the children successfully with chemotherapy, the fact that they developed leukemia during treatment raises another important safety-related issue that gene therapy researchers must address.NCRR/SEPASupported by a Science Education Partnership Award (SEPA) [No. 1 R25 RR16291-01] from the National Center for Research Resources, a component of the National Institutes of Health, Department of Health and Human Services. The contents provided here are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH.