UCLA stem cell gene therapy for sickle cell
disease advances toward clinical trials

Researchers at UCLA's Eli and Edythe Broad Center of
Regenerative Medicine and Stem Cell Research have
successfully established the foundation for using
hematopoietic (blood-producing) stem cells from the bone
marrow of patients with sickle cell disease to treat the
disease. The study was led by Dr. Donald Kohn, professor
of pediatrics and of microbiology, immunology and
molecular genetics.
Sickle cell disease causes the body to produce red blood
cells that are formed like the crescent-shaped blade of a
sickle, which hinders blood flow in the blood vessels and
deprives the body's organs of oxygen.
Kohn introduced an anti-sickling gene into the
hematopoietic stem cells to capitalize on the self-renewing
potential of stem cells and create a continual source of
healthy red blood cells that do not sickle. The breakthrough
gene therapy technique for sickle cell disease is scheduled
to begin clinical trials by early 2014. The study was
published online today ahead of press in the Journal of
Clinical Investigation.
Kohn's gene therapy approach, which uses hematopoietic
stem cells from a patient's own blood, is a revolutionary
alternative to current sickle cell disease treatments as it
creates a self-renewing normal blood cell by inserting a
gene that has anti-sickling properties into hematopoietic
stem cells. This approach also does not rely on the
identification of a matched donor, thus avoiding the risk of
rejection of donor cells. The anti-sickling hematopoietic
stem cells are transplanted back into the patient's bone
marrow and multiply the corrected cells that make red blood
cells without sickling.
"The results demonstrate that our technique of lentiviral
transduction is capable of efficient transfer and consistent
expression of an effective anti-sickling beta-globin gene in
human sickle cell disease bone marrow progenitor cells,
which improved the physiologic parameters of the resulting
red blood cells," Kohn said.
Kohn and colleagues found that in the laboratory the
hematopoietic stem cells produced new non-sickled blood
cells at a rate sufficient for significant clinical improvement
for patients. The new blood cells survive longer than sickled
cells, which could also improve treatment outcomes.
Sickle cell disease mostly affects people of Sub-Saharan
African descent, and more than 90,000 patients in the U.S.
have been diagnosed. It is caused by an inherited mutation
in the beta-globin gene that makes red blood cells change
from their normal shape, which is round and pliable, into a
rigid, sickle-shaped cell. Normal red blood cells are able to
pass easily through the tiniest blood vessels, called
capillaries, carrying oxygen to organs such as the lungs,
liver and kidneys. But due to their rigid structure, sickled
blood cells get stuck in the capillaries.
Current treatments include transplanting patients with
donor hematopoietic stem cells, which is a potential cure
for sickle cell disease, but due to the serious risks of
rejection, only a small number of patients have undergone
this procedure and it is usually restricted to children with
severe symptoms.
This study was supported in part by a Disease Team I Award
from the California Institute for Regenerative Medicine, the
state's stem cell research agency, which was created by a
voter initiative in 2004. The purpose of the disease team
program is to support research focused on one particular
disease that leads to the filing of an investigational new
drug application with the FDA within four years. The
program is designed to speed translational research —
research that takes scientific discoveries from the
laboratory to the patient bedside. This requires new levels
of collaboration between basic laboratory scientists,
medical clinicians, biotechnology experts and
pharmacology experts, to name a few.
Other support came from UCLA's Broad Stem Cell Research
Center and Jonsson Comprehensive Cancer Center, and
from the Ruth L. Kirschstein National Research Service
Award.
The Eli and Edythe Broad Center of Regenerative Medicine
and Stem Cell Research : UCLA's stem cell center was
launched in 2005 with a UCLA commitment of $20 million
over five years. A $20 million gift from the Eli and Edythe
Broad Foundation in 2007 resulted in the renaming of the
center. With more than 200 members, the Broad Stem Cell
Research Center is committed to a multi-disciplinary,
integrated collaboration of scientific, academic and medical
disciplines for the purpose of understanding adult and
human embryonic stem cells. The center supports
innovation, excellence and the highest ethical standards
focused on stem cell research with the intent of facilitating
basic scientific inquiry directed towards future clinical
applications to treat disease. The center is a collaboration
of the David Geffen School of Medicine, UCLA's Jonsson
Cancer Center, the Henry Samueli School of Engineering and
Applied Science and the UCLA College of Letters and
Science.
For more news, visit the UCLA Newsroom

USE OF GENE THERAPY IN SICKLE CELL DISEASE
Sickle cell disease is a monogenic disorder that occurs due to point mutation at position 6 of Beta globin chain of hemoglobin molecule in which valine is being substitute for glutamic acid.
USE OF GENE THERAPY IN SICKLE CELL DISEASE
Sickle cell disease is a monogenic disorder that occurs due to point mutation at position 6 of Beta globin chain of hemoglobin molecule in which valine is being substitute for glutamic acid.