International Gene Therapy Trial for ‘Bubble Boy’ Disease Shows Promising Early Results
December 07, 2013
Eight of nine children treated doing well, according to data presented to American Society of Hematology
NEW ORLEANS, Dec. 7, 2013—Researchers reported promising outcomes data for the
first group of boys with X-linked severe combined immunodeficiency
syndrome (SCID-X1), 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. 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 (Abstract #715) 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.
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.
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
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.
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.
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.