Breaking News
December 12, 2018 - Gun violence is a public health issue: One physician’s story
December 12, 2018 - The Science of Healthy Aging
December 12, 2018 - Yes to yoghurt and cheese: New improved Mediterranean diet
December 12, 2018 - Researchers uncover a number of previously unknown insecticide resistance mechanisms
December 12, 2018 - Regulating the immune system’s ‘regulator’
December 12, 2018 - In breaking bad news, the comfort of silence
December 12, 2018 - Study finds upward link between alcohol consumption and physical activity in college students
December 12, 2018 - FDA issues warning letter to Zhejiang Huahai Pharmaceutical involved in valsartan recall
December 12, 2018 - Presence of antiphospholipid antibodies tied to first-time MI
December 12, 2018 - New study could help inform research on preventing falls
December 12, 2018 - Women and men with heart attack symptoms receive different care from EMS
December 12, 2018 - Disrupted biological clock can contribute to onset of diseases, USC study shows
December 12, 2018 - New publications generate controversy over the value of reducing salt consumption in populations
December 12, 2018 - New data from TAILORx trial confirms lack of chemo benefit regardless of race or ethnicity
December 12, 2018 - Specific class of biomarkers can accurately indicate the severity of cancer
December 12, 2018 - Meds Taken Do Not Vary With ADL Impairment in Heart Failure
December 12, 2018 - Long-term study shows that HIV-2 is deadlier than previously thought
December 12, 2018 - People living near oil and gas wells show early signs of cardiovascular disease
December 12, 2018 - IONTAS founder and pioneer in phage display technology attends Nobel Prize Award Ceremony
December 12, 2018 - People who eat red meat have high levels of chemical associated with heart disease, study finds
December 12, 2018 - New method uses water molecules to unlock neurons’ secrets
December 12, 2018 - Genetics study offers hope for new acne treatment
December 12, 2018 - New computer model predicts prostate cancer progression
December 12, 2018 - Nobel Laureates lecture about immune checkpoint therapy for cancer treatment
December 12, 2018 - More Illnesses From Tainted Romaine Lettuce Reported
December 12, 2018 - Aspirin could reduce HIV infections in women
December 12, 2018 - The EORTC Brain Tumor Group and Protagen AG collaborate to study immuno-competence of long-term glioblastoma survivors
December 12, 2018 - Insights into magnetotactic bacteria could guide development of biological nanorobots
December 12, 2018 - Sacrificial immune cells alert body to infection
December 12, 2018 - Low-salt diet may be more beneficial for females than males
December 12, 2018 - Major soil organic matter compound battles chronic wasting disease
December 12, 2018 - Findings may open up new ways to treat dwarfism and other ER-stress-related conditions
December 12, 2018 - New computational model provides clearer picture of shape-changing cells’ structure and mechanics
December 12, 2018 - 10 Facts on Patient Safety
December 12, 2018 - Poorest dying nearly 10 years younger than the rich in ‘deeply worrying’ trend for UK
December 12, 2018 - Innovative care model for children with ASD reduces use of behavioral drugs in ED
December 12, 2018 - Spending time in and around Hong Kong’s waters linked to better health and wellbeing
December 12, 2018 - Simple measures to prevent weight gain over Christmas
December 12, 2018 - Research advances offer hope for patient-tailored AML treatment
December 12, 2018 - Researchers discover a ‘blind spot’ in atomic force microscopy
December 12, 2018 - Sprayable gel could help prevent recurrences of cancer after surgery
December 12, 2018 - SLU researchers explore how fetal exposure to inflammation can alter immunity in newborns
December 12, 2018 - How do patients want to discuss symptoms with clinicians?
December 12, 2018 - Zinc chelation may be able to deliver drug to insulin-producing cells
December 12, 2018 - Brigham researchers develop automated, low-cost tool to predict a woman’s ovulation
December 12, 2018 - Some people with Type 2 diabetes may be testing their blood sugar more often than needed
December 12, 2018 - Slow-growing type of glioma may be vulnerable to immunotherapy, suggests study
December 12, 2018 - Study provides new information regarding microRNA function in cellular homeostasis of zebrafish
December 12, 2018 - Study provides new understanding of mysterious ‘hereditary swelling’
December 12, 2018 - Researchers shed new light on how to combat Shiga and ricin toxins
December 12, 2018 - Pregnant Women Commonly Refuse Vaccines
December 12, 2018 - Drug treatment could offer new hope for some patients with brain bleeding
December 12, 2018 - Health care financial burden of animal-related injuries is growing, study says
December 12, 2018 - Macrophage cells could help repair the heart following a heart attack, study finds
December 12, 2018 - Researchers develop new system for efficiently producing human norovirus
December 12, 2018 - New artificial intelligence-based system to differentiate between different types of cancer cells
December 11, 2018 - Brazilian professors propose guidelines for therapeutic use of melatonin
December 11, 2018 - Healthy Lifestyle Lowers Odds of Breast Cancer’s Return
December 11, 2018 - New research identifies two genes linked to serious congenital heart condition
December 11, 2018 - NIH Director talks science, STEM careers with preteens
December 11, 2018 - Disabling a Cellular Antivirus System Could Improve Gene Therapy
December 11, 2018 - New tool swiftly provides accurate measure of patients’ cognitive difficulties
December 11, 2018 - NICE releases new guidelines for diagnosis and management of COPD
December 11, 2018 - Without Obamacare penalty, think it’ll be nice to drop your plan? Better think twice
December 11, 2018 - Researchers capture high-resolution X-ray and NMR image of key immune regulator
December 11, 2018 - Natural flavonoid is effective at treating leishmanisis infections, study shows
December 11, 2018 - Avoidant grievers unconsciously monitor and block mind-wandering contents, study shows
December 11, 2018 - Study identifies how hantaviruses infect lung cells
December 11, 2018 - Improving PTSD care through genetics
December 11, 2018 - Dermatology providers show interest in recommending cannabinoids to patients
December 11, 2018 - Researchers to study effects of electroconvulsive therapy on Alzheimer’s patients with aggression
December 11, 2018 - Four dried fruits have lower glycemic index than starchy foods, study finds
December 11, 2018 - Optimization of drug dose sizes can reduce pharmaceutical wastage
December 11, 2018 - Ultrarestrictive opioid prescribing strategy linked with reduction in number of pills dispensed
December 11, 2018 - PET scans to optimize tuberculosis meningitis treatments and personalize care, study finds
December 11, 2018 - Researchers aim to identify and target high blood pressure indicators
December 11, 2018 - Researchers identify immune cell subset that may drive chronic inflammation
December 11, 2018 - Ezogabine treatment reduces motor neuron excitability in ALS patients, study shows
December 11, 2018 - One implant, two prices. It depends on who’s paying.
December 11, 2018 - Standardizing feeding practices improves growth trends for micro-preemies
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