Featured Research

from universities, journals, and other organizations

X-linked severe combined immunodeficiency syndrome: Gene therapy trial shows promising early results

Date:
December 8, 2013
Source:
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
Summary:
Researchers reported promising outcomes data for the first group of boys with X-linked severe combined immunodeficiency syndrome, a fatal genetic immunodeficiency also known as "bubble boy" disease, who were treated as part of an international clinical study of a new form of gene therapy. Its delivery mechanism was designed to prevent the leukemia that arose a decade ago in a similar trial in Europe.

Researchers reported promising outcomes data for the first group of boys with X-linked severe combined immunodeficiency syndrome (SCID-X1), a fatal genetic immunodeficiency, who were treated as part of an international clinical study of a new form of gene therapy. The mechanism used to deliver the gene therapy is designed to prevent the serious complication of leukemia that arose a decade ago in a similar trial in Europe, when one-quarter of boys treated developed the blood cancer.

Eight of the nine boys registered to date in the new trial are alive and well, with functioning immune systems and free of infections associated with SCID-X1, between nine and 36 months following treatment, according to Sung-Yun Pai, MD, a pediatric hematologist-oncologist from Dana-Farber/Boston Children's Cancer and Blood Disorders Center. She presented the findings at the 55th annual meeting of the American Society of Hematology on behalf of the Transatlantic Gene Therapy Consortium (TAGTC). The investigators continue to monitor the children for signs of treatment-associated leukemia, which developed three to five years post-treatment in the prior trial. They point to surrogate biological markers that give them hope the viral vector used to deliver the new treatment is safe.

"These results show that the new vector appears to retain efficacy and, at least in preliminary studies, may be safer," said David A. Williams, MD, a leader of Dana-Farber/Boston Children's, who is chief of the Division of Hematology/Oncology at Boston Children's Hospital, associate chair of pediatric oncology at Dana-Farber Cancer Institute, and principal investigator for the gene therapy trial's U.S. sites.

Of the eight patients, seven are actively producing T cells, which are critical components of a healthy immune system. Six of these seven have met the trial's primary endpoint: a T-cell count greater than 300 cells per microliter of blood and T-cell proliferation in response to stimulation with phytohemagglutinin. The one patient among the seven who is producing T cells but has not yet achieved 300 cells/microliter will receive a second round of gene therapy next month.

The eighth surviving patient underwent a cord blood stem cell transplant after the gene therapy treatment failed to stimulate T-cell production. The lone fatality was caused by an overwhelming adenovirus infection present at the time the child entered the trial.

At the heart of the trial is a self-inactivating vector used to ferry the gene for the IL-2 receptor gamma subunit (IL2RG) into a patient's hematopoietic (blood-forming) stem cells. Once the gene is inserted, the cells are returned to the patient. IL2RG fuels the development and growth of immune cells and is a key component of normal immune system development. In children born with SCID-X1, the gene carries a mutation that renders it inactive.

The viral vector used in the study is a modified gammaretrovirus, a member of a family of viruses able to insert genetic cargo into the genome of mammalian cells and drive expression of the inserted genes. The vector has been engineered to avoid the leukemia that halted the previous SCID-X1 gene therapy effort.

Analyses of T cells from the participants in the current trial suggest that the new vector avoided genomic sites known to contribute to leukemia development. The study team will continue to keep a close eye on the patients for any signs of abnormal T-cell growth.

"Our preliminary data suggest that this new vector approach appears to be as effective as the previous vector, and may avoid the long-term risk of leukemia," said Pai. "We are closely monitoring the patients to evaluate their long-term risks, but the excellent responses we have seen thus far give us hope."

"This study represents a unique approach to international collaboration by leading pediatric researchers to quickly address the previous adverse events caused by gammaretrovirus-based vectors," Williams said. "Working together, this group of scientists did the basic studies needed to develop and test a new vector, guide the new trial through a complicated regulatory review process and begin quickly enrolling patients."

The study's U.S. sites are supported by the National Institute of Allergy and Infectious Diseases (grant number U01AI087628) and the National Heart Lung and Blood Institute's Product Assistance for Cellular Therapies Program.


Story Source:

The above story is based on materials provided by Dana-Farber/Boston Children's Cancer and Blood Disorders Center. Note: Materials may be edited for content and length.


Cite This Page:

Dana-Farber/Boston Children's Cancer and Blood Disorders Center. "X-linked severe combined immunodeficiency syndrome: Gene therapy trial shows promising early results." ScienceDaily. ScienceDaily, 8 December 2013. <www.sciencedaily.com/releases/2013/12/131208090337.htm>.
Dana-Farber/Boston Children's Cancer and Blood Disorders Center. (2013, December 8). X-linked severe combined immunodeficiency syndrome: Gene therapy trial shows promising early results. ScienceDaily. Retrieved September 23, 2014 from www.sciencedaily.com/releases/2013/12/131208090337.htm
Dana-Farber/Boston Children's Cancer and Blood Disorders Center. "X-linked severe combined immunodeficiency syndrome: Gene therapy trial shows promising early results." ScienceDaily. www.sciencedaily.com/releases/2013/12/131208090337.htm (accessed September 23, 2014).

Share This



More Health & Medicine News

Tuesday, September 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Costs Keep Mounting

Ebola Costs Keep Mounting

Reuters - Business Video Online (Sep. 23, 2014) The WHO has warned up to 20,000 people could be infected with Ebola over the next few weeks. As Sonia Legg reports, the implications for the West African countries suffering from the disease are huge. Video provided by Reuters
Powered by NewsLook.com
Ebola Cases Could Reach 1.4 Million Within 4 Months

Ebola Cases Could Reach 1.4 Million Within 4 Months

Newsy (Sep. 23, 2014) Health officials warn that without further intervention, the number of Ebola cases in Liberia and Sierra Leone could reach 1.4 million by January. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Cases to Triple in Weeks Without Drastic Action

WHO: Ebola Cases to Triple in Weeks Without Drastic Action

AFP (Sep. 23, 2014) The number of Ebola infections will triple to 20,000 by November, soaring by thousands every week if efforts to stop the outbreak are not stepped up radically, the WHO warned in a study on Tuesday. Duration: 01:01 Video provided by AFP
Powered by NewsLook.com
5 Ways Men Can Prevent Most Heart Attacks

5 Ways Men Can Prevent Most Heart Attacks

Newsy (Sep. 23, 2014) No surprise here: A recent study says men can reduce their risk of heart attack by maintaining a healthy lifestyle, which includes daily exercise. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins