(Press-News.org) In a small study that included seven children and teens with Wiskott-Aldrich syndrome, a rare immunodeficiency disorder, use of gene therapy resulted in clinical improvement in infectious complications, severe eczema, and symptoms of autoimmunity, according to a study in the April 21 issue of JAMA, a theme issue on child health.
Wiskott-Aldrich syndrome (WAS) is caused by loss-of-function mutations in the WAS gene. The condition is characterized by thrombocytopenia (low platelet count), eczema, and recurring infections. In the absence of definitive treatment, patients with classic WAS generally do not survive beyond their second or third decade of life. Partially human leucocyte antigen (HLA) antigen-matched allogeneic (donated from another individual) hematopoietic stem cell (HSC) transplantation is often curative, but is associated with a high incidence of complications. Gene therapy based on transplantation of autologous (from the same individual) genecorrected HSCs may be an effective and potentially safer alternative. This procedure involves the removal and treatment of the patient's own blood stem cells, and their return to the patient by intravenous injection.
Marina Cavazzana, M.D., Ph.D., of Necker Children's Hospital, Paris, France, and colleagues assessed the outcomes and safety of autologous HSC gene therapy in patients with Wiskott-Aldrich syndrome. Gene-corrected autologous HSCs were infused in 7 patients (age range, 0.8-15.5 years) with severe Wiskott-Aldrich syndrome lacking HLA antigen-matched related or unrelated HSC donors. Patients were enrolled in France and England and treated between December 2010 and January 2014. Follow-up of patients in this intermediate analysis ranged from 9 to 42 months.
Among 6 of the 7 patients, there was clinical improvement after gene therapy, which was well tolerated. One patient died of preexisting, treatment-refractory infectious disease. In the 6 surviving patients, the infectious complications resolved after gene therapy, and prophylactic (preventative) antibiotic therapy was successfully discontinued in 3 cases. Severe eczema resolved in all affected patients, as did signs and symptoms of autoimmunity.
No severe bleeding episodes were recorded after treatment, and at last follow-up, all 6 surviving patients were free of blood product support. Hospitalization days were reduced from a median of 25 days during the 2 years before treatment to a median of 0 days during the 2 years after treatment.
The authors note that the interpretation of the results of this type of study is constrained by the small number of patients. "We therefore cannot draw conclusions on long-term outcomes and safety. Further follow-up of these patients and those reported in a similar study last year, together with additional clinical trials of this therapy, are therefore necessary."
(doi:10.1001/jama.2015.3253; Available pre-embargo to the media at http://media.jamanetwork.com)
Editor's Note: This study was sponsored by Genethon, Evry, France. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.
Editorial: An Emerging Era of Clinical Benefit From Gene Therapy
In an accompanying editorial, Harry L. Malech, M.D., of the National Institutes of Health, Bethesda, Md., and Hans D. Ochs, M.D., of the University of Washington and Seattle Children's Research Institute, Seattle, write that this study provides strong evidence that this type of gene therapy achieves substantial restoration of immune function associated with prolonged clinical benefit to patients with severe WiskottAldrich syndrome.
They add that the impressive clinical response seen in the study was achieved in the context of a long line of research by many groups of investigators striving toward the goal of clinically beneficial gene therapy. "Taken together, the available evidence demonstrates substantial sustained clinical benefit following gene therapy for certain diseases."
"At a time when many are championing personalized medicine, no advance is as representative of that fundamental biological approach as gene therapy."
(doi:10.1001/jama.2015.2055; Available pre-embargo to the media at http://media.jamanetwork.com)
Editor's Note: Please see the article for additional information, including financial disclosures, funding and support, etc.
INFORMATION:
In a study that included approximately 95,000 children with older siblings, receipt of the measles-mumps-rubella (MMR) vaccine was not associated with an increased risk of autism spectrum disorders (ASD), regardless of whether older siblings had ASD, findings that indicate no harmful association between receipt of MMR vaccine and ASD even among children already at higher risk for ASD, according to a study in the April 21 issue of JAMA, a theme issue on child health.
Although a substantial body of research over the last 15 years has found no link between the MMR vaccine ...
A 24 week parent training program, which provided specific techniques to manage disruptive behaviors of children with autism spectrum disorder, resulted in a greater reduction in disruptive and noncompliant behavior compared to parent education, according to a study in the April 21 issue of JAMA, a theme issue on child health.
Autism spectrum disorder (ASD) affects an estimated 6 per 1,000 children worldwide and is a major public health challenge. As many as 50 percent of children with ASD exhibit behavioral problems, including tantrums, noncompliance, aggression, and ...
In a pilot study that included children at high risk for type 1 diabetes, daily high-dose oral insulin, compared with placebo, resulted in an immune response to insulin without hypoglycemia, findings that support the need for a phase 3 trial to determine whether oral insulin can prevent islet autoimmunity and diabetes in high-risk children, according to a study in the April 21 issue of JAMA, a theme issue on child health.
A few specific proteins are often the trigger for immune responses that cause autoimmune diseases. This has led to the experimental use of antigenspecific ...
The incidence of a potentially life-threatening complication of diabetes, diabetic ketoacidosis, in youth in Colorado at the time of diagnosis of type 1 diabetes increased by 55 percent between 1998 and 2012, suggesting a growing number of youth may experience delays in diagnosis and treatment, according to a study in the April 21 issue of JAMA, a theme issue on child health.
Diabetic ketoacidosis (DKA) at the time of type 1 diabetes (T1D) diagnosis has detrimental long-term effects and is characterized by dangerously high blood sugar and the presence of substances in ...
A multi-site study sponsored by the National Institute of Mental Health (NIMH) finds young children with autism spectrum disorder and serious behavioral problems respond positively to a 24-week structured parent training. The benefits of parent training endured for up to six months post intervention.
Published in the April 21 issue of the Journal of the American Medical Association the study found parent training was more effective in reducing disruptive and aggressive behavior than 24 weeks of parent education. Parent training provided parents with specific strategies ...
Researchers from the University of Tokyo have revamped an old e-paper concept to make an inexpensive handwriting-enabled e-paper well suited to large displays like whiteboards. They describe the e-paper in the Journal of Applied Physics, from AIP Publishing.
Traditional ink and paper is convenient for both reading and writing. In e-paper development the writing feature has generally lagged behind. Handwriting-enabled displays mainly show up in the inexpensive, but feature-limited realm of children's toys, and in the high-end realm of touch-screen e-readers and smart ...
French teams from CIC Biothérapie (AP-HP/Inserm), from pediatric hematology department of Necker Hospital for Children (AP-HP), led by Marina Cavazzana, Salima Hacein Bey Albina and Alain Fischer and from Genethon led by Anne Galy (Genethon/Inserm UMR-S951), and English teams from UCL Institute of Child Health and Great Ormond Street Hospital in London led by Adrian Thrasher and Bobby Gaspar demonstrated the efficacy of gene therapy treatment for Wiskott-Aldrich Syndrome (WAS). Six children that were treated and followed for at least 9 months had their immune system ...
BOULDER, Colo. -- In another advance at the far
frontiers of timekeeping by National Institute of
Standards and Technology (NIST) researchers, the
latest modification of a record-setting strontium atomic
clock has achieved precision and stability levels that
now mean the clock would neither gain nor lose one
second in some 15 billion years*--roughly the age of
the universe.
Precision timekeeping has broad potential
impacts on advanced communications, positioning technologies (such as GPS) and many
other technologies. Besides keeping future technologies on schedule, ...
Scientists from the DFG Center for Regenerative Therapies Dresden, TU Dresden and the Institut für Diabetesforschung, Helmholtz Zentrum München, together with researchers from Vienna, Bristol and Denver (USA) have successfully completed the first step in development of an insulin vaccine to prevent type 1 diabetes.
As reported by these diabetes researchers in the current edition of the renowned scientific journal JAMA, evaluations of the international Pre-POINT study point to a positive immune response in persons at risk for the disease who were given oral doses ...
AURORA, Colo. (April 21, 2015) - The incidence of a potentially life-threatening complication of diabetes, called diabetic ketoacidosis, increased by 55 percent between 1998 and 2012 in youth in Colorado, according to a study by researchers from the Barbara Davis Center for Childhood Diabetes and the University of Colorado School of Medicine on the Anschutz Medical Campus.
The finding is published in the April 21 issue of JAMA.
Diabetic ketoacidosis (DKA) at the time of type 1 diabetes diagnosis has detrimental long-term effects and is characterized by dangerously high ...
