Early Gene Therapy Results in Wiskott-Aldrich Syndrome Promising
December 06, 2015
(News Release)
Four children treated
in U.S. trial show improvements, will continue to be monitored for long-term
outcomes
ORLANDO,
Fla.
– Researchers reported promising preliminary outcomes for the first four
children enrolled in a U.S. gene therapy trial for
Wiskott-Aldrich syndrome (WAS), a life-threatening genetic blood and immune
disorder, at the 57th annual meeting of the American Society of Hematology
(abstract #260).
All
four boys are alive and have improved between nine and 24 months following
treatment, according to study principal investigator Sung-Yun Pai, MD, a pediatric
hematologist-oncologist from Dana-Farber/Boston Children's Cancer and
Blood Disorders Center. Since undergoing treatment, none of the boys of have
experienced bleeding events or severe WAS-related infections. In addition, all four
have experienced improvements in immunologic symptoms and variable improvements
in platelet count. The two patients who had required medication to stimulate
platelet production prior to undergoing gene therapy are no longer on those
medicines.
It
is too early, however, to draw conclusions about long-term outcomes. The study protocol
calls for the children to be monitored for 15 years in order to assess the
treatment's safety and efficacy.
WAS
is caused by mutations that lead to the loss or dysfunction of the WAS gene, which is found on the X
chromosome. The condition, which occurs only in boys, affects the development and
function of T-cells and platelets, leaving patients vulnerable to bleeding,
eczema and infections. The only curative treatment is a hematopoietic (blood-forming)
stem cell transplant from a compatible donor. However, it is often difficult to
identify an appropriate match.
The
trial centers on a viral vector, which is used to insert functional copies of
the WAS gene into a patient's
hematopoietic (blood-forming) stem and progenitor cells, which give rise to all
cell types found in the blood and the immune system. These cells are collected
from the patient, exposed to the vector in the laboratory and, once the vector
inserts the gene and doctors have eradicated the patient’s own blood system
with chemotherapy, are returned to the patient via intravenous transfusion. The
vector is a self-inactivating lentivirus — a member of a family of viruses that
can insert genes into mammalian cells and drive expression of those genes —
that has been engineered to avoid triggering the development of leukemia, a
complication seen in previous gene therapy trials for immunodeficiency
syndromes, including WAS.
The
study's variable results to date raise questions about which factor is most
important to the success of gene therapy for any given individual with WAS: the
number of WAS gene copies the vector
inserts into the patient's cells, the number of modified cells given to a
patient, or how effectively the patient's native blood system is eliminated before
the modified cells are infused.
"Putting
the data that we have together, we get the sense that these factors all
matter," said Pai, who presented the data on behalf of a team of
investigators from the U.S., Turkey, Japan and Chile. "We suspect that infusing
a few cells that each have two or three copies of the WAS gene may be better than infusing many cells with only one copy
of the gene each. But with the very small number of patients we've treated to
date, our data are only suggestive."
Read the story of
Emir Seyrek, the first child to be enrolled in this trial, on Boston Children's
Hospital's Vector and Thriving blogs.