Breaking News
May 26, 2018 - CRISPR-Cas9-based strategy allows researchers to precisely alter hundreds of different genes
May 26, 2018 - UT Southwestern-led researchers find new way to determine prognosis of invasive kidney cancer
May 26, 2018 - Researchers develop film to prevent bacteria from growing on dental retainers and aligners
May 26, 2018 - Mobile health intervention for people with serious mental illness as effective as clinic-based treatment
May 26, 2018 - Vaginal estradiol tablets outperform moisturizers when treating vulvovaginal problems
May 26, 2018 - Researchers call for new genetic tests for congenital diseases
May 26, 2018 - KHN’s ‘What the Health?’ Campaign promises kept, plus ‘nerd reports’
May 26, 2018 - Lung-on-a-chip technology could streamline drug-testing for pulmonary fibrosis
May 26, 2018 - Study finds early antibiotic initiation for majority of premature infants
May 26, 2018 - New environmental monitoring project finds increased numbers of deer ticks in Southern Indiana
May 26, 2018 - Pediatricians Should Advocate for Life Support Training
May 26, 2018 - Cannabidiol significantly reduces seizures in patients with severe form of epilepsy
May 26, 2018 - Allergies can have serious, far-reaching consequences on adolescents
May 26, 2018 - Scientists develop lab-based system to study mechanisms of common liver disease
May 25, 2018 - New guidelines may help pathologists to more accurately classify and diagnose invasive melanoma
May 25, 2018 - Immune cells promote lung cancer metastases by forming clots in tumors, study finds
May 25, 2018 - Can Excess Weight in Toddlers Cause Brain Drain?
May 25, 2018 - Studying insight
May 25, 2018 - Researchers reveal potent new mechanism of action for treatment of IBD
May 25, 2018 - Study shows lack of follow-up care for patients with concussion
May 25, 2018 - Study establishes the importance of haploid cells
May 25, 2018 - Coveted BMJ award bestowed on The Clatterbridge Cancer Center
May 25, 2018 - AACN outlines evidence-based protocols and clinical strategies to manage alarms
May 25, 2018 - Origami inspires researchers to develop new solution for tissue regeneration
May 25, 2018 - Melorheostosis – Genetics Home Reference
May 25, 2018 - Non-addictive pain medication changing therapy for substance use disorders
May 25, 2018 - Delayed lactate measurements in sepsis patients increase risk of in-hospital death
May 25, 2018 - Researchers identify novel epigenetic mutations as cause of neurodevelopmental, congenital disorders
May 25, 2018 - UD researchers examine connection between DNA replication in HPV and cancer
May 25, 2018 - Researchers identify neurons that play key role in aggressive behavior
May 25, 2018 - Snail’s eye inspires new type of RIOCATH urinary catheter
May 25, 2018 - Russian researchers develop high-tech device-transformer for ultrasound examination
May 25, 2018 - Researchers discover unexpected chemosensor pathway for predator odor-evoked innate fear behaviors
May 25, 2018 - Researchers build 3-D printer that offers sweet solution to making detailed structures
May 25, 2018 - Nearly one in three people know someone addicted to opioids
May 25, 2018 - Research suggests link between faulty gene, alcohol, and heart failure
May 25, 2018 - New findings could help fine-tune treatment for cancer patients
May 25, 2018 - New cancer treatment approach targets specific sugar receptors
May 25, 2018 - Skin responsible for uptake of cancer-causing compounds during barbecuing than lungs
May 25, 2018 - Early-onset cannabis use linked to further drug abuse problems
May 25, 2018 - Covered California takes aim at hospital C-section rates
May 25, 2018 - FDA Approves Palynziq (pegvaliase-pqpz) for the Treatment of Adults with Phenylketonuria
May 25, 2018 - Arthritis Glossary
May 25, 2018 - Study links breast cancer to the body’s internal clock
May 25, 2018 - Strenuous exercise in teenage years may protect against height loss later in life
May 25, 2018 - FDA approves novel enzyme therapy for adults with rare and serious genetic disease
May 25, 2018 - New research project aims at developing effective interventions for kids with DLD
May 25, 2018 - Middlemen who save $$ on medicines — but maybe not for you
May 25, 2018 - Study sheds new light on sharp rise in fatal drug overdoses in recent years
May 25, 2018 - Students propose revision of listeriosis guidelines for safer pregnancy
May 25, 2018 - TNFi Exposure In Utero Does Not Up Serious Infection Risk
May 25, 2018 - Organization of cells in the inner ear enables the sense and sensitivity of hearing
May 25, 2018 - Yoga May Be Right Move Against Urinary Incontinence
May 25, 2018 - Drinking recommended amount of milk could protect obese children against metabolic syndrome
May 25, 2018 - New cytokine network can repair tissue damage in the intestine, study finds
May 25, 2018 - Lyme disease researcher dispels misconceptions about ticks and provides prevention tips
May 25, 2018 - Penn researchers find link between social media usage and underage drinking
May 25, 2018 - Unique nanotechnology method to simplify skin disease diagnosis
May 25, 2018 - Study reveals new protective mechanism for tumor cells in breast cancer
May 25, 2018 - FRAME Alternatives Laboratory chosen for major European liver research collaboration
May 25, 2018 - Study shows yogurt may dampen chronic inflammation linked to multiple diseases
May 25, 2018 - Invasive cancers that are born to be bad show detectable differences from harmless tumors
May 25, 2018 - Study identifies new mechanism involved in development of Lou Gehrig’s disease
May 25, 2018 - UAB professor receives award for malaria prevention study in pregnant women in Cameroon
May 25, 2018 - Study provides blueprint of how fruit flies can be used to screen potentially pathogenic human genes
May 25, 2018 - New drug-delivering nanoparticle could offer better way to treat brain tumors
May 25, 2018 - Kessler Foundation scientists compare two tests for assessing learning in individuals with MS
May 25, 2018 - Stroke Symptoms and Diagnosis (Beyond the Basics)
May 25, 2018 - Protein goes against the family to prevent cancer
May 25, 2018 - Drugmakers blamed for blocking generics have milked prices and cost U.S. billions
May 25, 2018 - Speakers announced for National Medicines Symposium 2018
May 25, 2018 - GSK Receives FDA Approval of Arnuity Ellipta for Asthma in Children From 5 Years of Age
May 25, 2018 - Pfizer settles kickback case related to copay assistance for $24m
May 25, 2018 - Nuclear pore functions are essential for T cell survival
May 25, 2018 - Study defines molecular basis to explain connection between mother’s nutrition and infant growth
May 24, 2018 - IHI hosts representatives to develop a national action plan for patient safety
May 24, 2018 - Zika detection breakthrough by University of Queensland
May 24, 2018 - FDA Alert: 95% Ethyl Alcohol Product by Ethanol Extraction: Recall
May 24, 2018 - New method allows scientists to study how HIV persists
May 24, 2018 - Study reveals rate of vertebral and non-vertebral fractures in children with leukemia
Gene therapy improves immunity in babies with ‘bubble boy’ disease

Gene therapy improves immunity in babies with ‘bubble boy’ disease

image_pdfDownload PDFimage_print
St. Jude gene therapy improves immunity in babies with 'bubble boy' disease
Ewelina Mamcarz, M.D., presents research at the 2017 ASH conference that indicates that the St. Jude XSCID gene therapy has been well tolerated and effective for infants as young as 2 months old. Credit: Peter Barta / St. Jude Children’s Research Hospital.

Early evidence suggests that gene therapy developed at St. Jude Children’s Research Hospital will lead to broad protection for infants with the devastating immune disorder X-linked severe combined immunodeficiency disorder. Preliminary results from the ongoing, multicenter study were included in the press program here today at the 59th annual meeting of the American Society of Hematology.

Approximately four months after treatment, five of the seven patients enrolled in the St. Jude clinical trial had immune systems for the first time. The patients no longer require protective isolation. Four patients have started making serum immunoglobulins (antibodies) for the first time. One has stopped monthly immunoglobulin supplementation and recently received his first set of vaccinations.

“These results are an exciting early indication that this gene therapy is well tolerated and effective in infants as young as 2 months old with this devastating inherited immune disorder,” said Ewelina Mamcarz, M.D., an assistant member of the St. Jude Department of Bone Marrow Transplantation and Cellular Therapy. She spoke at the press conference and will present the findings Sunday, Dec. 10.

Immune protection will likely return to the last patient. There is evidence that the seventh patient, who joined the study six weeks ago, now carries the vector in his immune cells. No serious or unexpected treatment-related complications have been reported.

The results are the first involving infants with XSCID treated with the St. Jude lentiviral vector. Researchers previously reported promising results in adolescents and young adults with XSCID who were treated with the St. Jude vector and low-dose chemotherapy after bone marrow transplantation failed to restore adequate immune protection.

The patients in this study were between the ages of 2 and 13 months and born with a disorder caused by a mutation in the IL2RG gene. The mutation primarily affects boys and leaves them with little or no immune protection. The disorder is also known as “bubble boy” disease, a reference to the measures used to protect patients from infections and other threats. Untreated, individuals usually die of overwhelming infections within months.

Currently, transplantation with a tissue-matched sibling donor is the standard treatment for XSCID. More than 80 percent of XSCID patients, including the infants in this study, do not have matched sibling donors. These patients must rely on unrelated donors or parent donors, who are partial genetic matches. Such transplants are less likely to fully restore immune function and are associated with potentially severe treatment-related complications.

In response, St. Jude researchers have re-engineered a lentivirus to function as a vector to ferry a normal copy of IL2RG into the patients’ hematopoietic stem cells. The vector includes novel features to enhance safety and effectiveness. The features include genetic insulators to block activation of genes adjacent to the IL2RG DNA insertion site. The design aims to ensure gene therapy will not lead to leukemia by inadvertently activating an oncogene in the patient’s hematopoietic stem cells.

The treatment involves removing the patient’s bone marrow and letting the hematopoietic stem cells incubate with the lentiviral vector carrying the normal gene. The stem cells are then processed and returned to the patient via transfusion. Prior to transfusion, patients receive low-dose chemotherapy with the drug busulfan. Unlike the prior studies, the level of busulfan in the patient’s blood is pharmacologically targeted to avoid variability in blood levels and improve safety. The chemotherapy is designed to make space in the bone marrow for the gene-corrected hematopoietic stem cells to settle in and start working.

“These early results in infants reinforce hope that gene therapy will prove to be safe and effective at restoring immune function early in life,” said Brian Sorrentino, M.D., a member of the St. Jude Department of Hematology, who leads this study with Mamcarz.

Following gene therapy, levels of T, B and natural killer cells rose to near normal levels in five of the first six patients who enrolled in the study. The vast majority of the immune cells, including 100 percent of the T and natural killer cells, carried the normal gene that was carried in the lentiviral vector. 60 to 80 percent of the B cells also carried the normal gene. Previous gene therapy for XSCID did not lead to such high levels of genetic correction in all immune cell types.

In three of the five patients, 50 percent or more of the hematopoietic stem cells also carried the normal gene. “This suggests these patients will likely enjoy life-long immune protection without exposure to high-dose chemotherapy,” Mamcarz said. This level of bone marrow stem cell correction has not been achieved in prior gene therapy studies in XSCID infants.

The sixth patient included in the report received a booster dose of gene-corrected blood stem cells. Laboratory tests indicate T cells, including T cells with the correct gene, have begun to increase. “This was a complex patient,” Mamcarz said. The patient was being treated for severe neutropenia and a viral infection when he joined the study. In addition, maternal T cells had engrafted in his bone marrow, complicating efforts to restore his own genetically corrected blood stem cells to his bone marrow.


Explore further:
Gene therapy shows early success against ‘Bubble Boy’ disease

Provided by:
St. Jude Children’s Research Hospital

Tagged with:

About author

Related Articles