Treatment for Growth Failure in Patients With X-Linked Severe Combined Immunodeficiency: Phase 2 Study of Insulin-Like Growth Factor-1
January 10, 2012Purpose
This study will evaluate the safety and effectiveness of insulin-like growth factor-1 (IGF-1) to treat patients with X-linked severe combined immunodeficiency (XSCID). Those who have XSCID lack white blood cells that protect their bodies from invasion by all types of germs. IGF-1 is the main hormone responsible for the body’s growth and metabolism. As a medication, IGF-1 is Increlex[(Trademark)] (mecasermin),
Patients ages 2 to 20 who have not yet begun puberty, have a diagnosis of XSCID, and are shorter than the 3rd percentile for their age may be eligible for this study. This study will last about 3 years, and patients’ visits will be scheduled at 3-month intervals. Patients will have a physical history and exam, X-rays, electrocardiogram, blood tests, and body measurements.
Patients will take estradiol orally for 2 days, to help avoid false results of growth hormone (GH) levels in blood samples. Then provocation testing is done, with two tests back to back. It determines blood levels of GH and the body’s response to testing with drugs called arginine and clonidine. Patients are admitted to the pediatric inpatient unit and will have an intravenous (IV) line placed in the arm. Arginine is given by IV over 30 minutes, and blood samples are taken. Right after arginine testing, the clonidine tablet is given. The IGF-1 generation test is then done to see if the body makes IGF-1 as a product in response to injections of GH for 5 consecutive days. This test does not require that patients are inpatients, but after Day 8, patients must be admitted to the pediatric unit to have blood sampling, start Increlex injections, and start close monitoring of blood sugar levels. They will learn how to do a self-injection and follow other advice. They will complete records about the injection site, symptoms, and side effects-keeping records for at least the first 2 days after going home, with each dose change, and as needed. Patients stick their fingertip and place a small drop of blood on a blood sugar monitoring strip. The strip is put into a glucometer-a small hand-held device to measure the blood sugar level. Patients will be instructed to always have a source of sugar available in case blood sugar is too low.
linkback url: http://clinicaltrials.gov/ct2/show/NCT00490100?term=xscid&rank=1
Gene therapy works for ‘Bubble Boy’ disease
August 24, 2011Gene therapy works for ‘Bubble Boy’ disease
(WebMD)
Nine years after getting gene therapy for a rare, inherited immune system disorder often called “bubble boy disease,” 14 out of 16 children are doing well, researchers report.
The children were born with severe combined immunodeficiency disease (SCID). They got an experimental gene therapy in the U.K.
A new report shows that nine years later, 14 of the 16 children had working immune systems and were leading normal lives.
“These children, who would have died very young without treatment, are participating in life as fully as their brothers and sisters,” researcher H. Bobby Gaspar, MD, PhD, tells WebMD. “Most of them are going to school, playing ball, and going to parties.”
Few Treatment Options for SCID
Children with SCID carry genetic defects that prevent their immune systems from working. Without treatment, most die from infection in their first two years of life.
One exception was David Vetter, a Texas boy born in 1971. Vetter lived in a specially constructed sterile plastic bubble from birth until his death at age 12. He became famous as the “bubble boy,” and his story made many people aware of SCID for the first time.
For decades, the treatment has been to get transplants of blood-forming stem cells from the bone marrow of matched siblings or other donors who have healthy immune systems.
Such transplants can effectively cure the disorder. But only about one in five children with SCID have a perfectly matched donor.
Bone marrow from partially matched donors can also be used. But those mismatched transplants are much more risky. About one in three children who have them die from the procedure.
About a decade ago, researchers discovered a way to manipulate a patient’s own genes to manufacture the missing part of the gene needed to make the immune system work.
Since that time, gene therapy has been used to treat dozens of children with SCID, says UCLA researcher Donald B. Kohn, MD, who did not participate in the U.K. study.
How the Children Fared
“The big picture here is that almost 10 years down the line, all of these children are alive and 14 of 16 have been able to correct their immune systems,” Gaspar says. “With [mismatched] transplants, we would have lost two to four of them.”
The 16 children with SCID who got the gene therapy ranged in age from 6 months to 3 years. Four of them had the ADA-deficiency type of SCID. The other kids had the X1 form of SCID. Those are the two most common types of SCID.
For most of the children, gene therapy was a success. But one boy who had the X1 form of SCID developed treatment-related leukemia. The complication was not unexpected, Gaspar says, because four children with the X1 from of SCID in a French study had developed leukemia after getting the gene therapy.
Gaspar says researchers learned from those cases and have modified the treatment in hopes of reducing the risk for patients with the X1 form of the disorder.
Kohn says gene therapy should be considered the treatment of choice for children with ADA-deficient SCID who do not have perfect bone marrow donor matches. It may prove to be a better choice for patients with perfect donor matches, too, he says.
As for the X1 form of the disease, Kohn says it remains to be seen if the new approach to gene delivery works and has less risk of leukemia.
Lessons learned from the SCID trials have spurred studies to find effective gene-based treatments for other blood cell diseases, including sickle cell anemia, Kohn notes.
“The history of gene therapy research can be summarized as, ‘Two steps forward and one step back.’ We retrench, we learn, and then we move forward again,” he says.
“Twenty years ago, nothing was working,” Kohn says. “Ten years ago, these treatments started to work, but with complications. The hope is that the next decade will bring highly effective treatments with few complications.”
Reviewed by Laura J. Martin, MD
linkback url: http://www.cbsnews.com/stories/2011/08/24/health/webmd/main20096859.shtml
‘Bubble Boy’ Kids Living Normally After Gene Therapy: Study
August 24, 2011‘Bubble Boy’ Kids Living Normally After Gene Therapy: Study
By Amanda Gardner
HealthDay Reporter
WEDNESDAY, Aug. 24 (HealthDay News) — More than a dozen children with so-called “bubble boy” disease are alive and well, with functioning immune systems, nine years after undergoing gene therapy to correct their disorder, researchers report.
Most of the patients attend school with other children, something that probably would have been fatal without treatment.
“The promise of gene therapy is being fulfilled, at least for these diseases, where a number of patients are walking around in good health because they had gene therapy,” said Dr. Donald Kohn, professor of microbiology, immunology and molecular genetics and pediatrics at the University of California, Los Angeles.
The disorder — severe combined immunodeficiency (SCID) — compromises the immune system so severely that children can’t fight off normally innocuous infections. The condition is rare, and the term “bubble boy” was coined after a Texas boy with the condition lived in a germ-free plastic bubble.
Only boys inherit the gene in question, and many born with SCID die in infancy.
Two studies published Aug. 24 in Science Translational Medicine detail the results of the gene-modifying treatment. Kohn wrote a perspective piece accompanying the studies.
Traditionally, the only treatment for SCID was stem cell transplantation in which immune cells from a matching donor are transferred to the patient. But it’s difficult to find matching donors and, even then, the patient’s body may reject the transplanted cells.
With gene therapy, clinicians remove the patient’s own bone marrow, isolate the stem cells, correct the gene and reinsert it into the patient, explained William J. Bowers, associate professor of neurology at the University of Rochester Medical Center in Rochester, N.Y.
The two current papers detail the success of gene therapy in two groups of patients: 10 boys with X-linked SCID (SCID-X1); and six with ADA-SCID, which involves a slightly different gene mutation. All were between 6 months and 39 months old.
Gene therapy successfully treated four of the six ADA-SCID patients.
All the SCID-X1 children recovered, although one developed leukemia. That boy is currently in remission, but leukemia has been a problem with previous gene therapy trials.
Last year, French researchers reported that eight of nine male infants born with SCID-X1 had recovered as a result of gene therapy. Unfortunately, almost half developed acute leukemia, one of whom died.
The virus vector used in this earlier trial inadvertently activated an oncogene, which led to the development of the leukemia, researchers said.
The latest research circumvented this problem by using a different virus vector.
“A cloud was thrown over the field several years ago and they’ve solved it nicely,” said Dr. Darwin Prockop, director of the Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine at Scott & White in Temple, Texas. “Very probably this can be used for other genetic diseases.”
“This field came on with huge promise, then hit a few bumps and now . . . we’re starting to see more and more of these successes,” added Bowers.
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