Gene Rx May Fight Severe Blood Disorder09/15/10
WEDNESDAY, Sept. 15 (HealthDay News) -- Patients suffering from
a severe, inherited blood disorder may one day benefit from a new
gene therapy and no longer need regular blood transfusions, new
However, far more study is needed to determine whether the
therapy is safe and effective. So far only one patient has received
the experimental treatment, and the researchers have followed him
for only three years.
The blood disorder -- beta-thalassemia -- occurs when a crucial
blood protein known as beta globin is missing from the red blood
cells that carry oxygen. Without beta globin, many of the red blood
cells die off, causing severe anemia and eventually death if the
person goes untreated.
Beta-thalassemia mostly affects people of Mediterranean, Middle
Eastern, Southeast Asian and Chinese descent. Some 100,000 children
are born with the disease each year around the world, according to
the March of Dimes, and untreated, those with the most severe form
usually die in childhood.
In those treated, the excess iron building up from the blood
transfusions must be removed with chelating drugs, which can cause
unpleasant side effects ranging from joint pain and vomiting to
vision and hearing problems.
And even though lifesaving treatments have greatly improved
prospects for long-term survival, those with the disorder are at
risk of heart failure and other life-threatening complications --
some related to the treatments themselves -- as they age.
Among those struggling with this illness -- and often losing --
was a teenager who volunteered for the gene therapy. Like many
others, he needed a matched donor for a stem cell transplant, but
none was available, the study noted.
"The patient was 18 years old when we first treated him and [had been] transfused monthly for most of his life," said lead researcher Dr. Philippe Leboulch, a professor of medicine and cell biology at the University of Paris in France.
Transfusions continued until a year after the treatment,
Leboulch said. "One year after the treatment he became
transfusion-independent," he said. "That has been the case for over
two years now."
For the study, Leboulch's team worked on a modified virus and
removed all the viral genes. They then replaced those genes with a
so-called globin gene. In addition, they added factors so the gene
would act only on red blood cells, where the iron-rich protein
known as hemoglobin normally carries oxygen throughout the
This new "gene" was then injected into the patient, where it
went on to repair the damaged globin gene and started producing
normal hemoglobin, Leboulch said.
"This is one more example of a gene therapy that starts to show a clinical benefit for patients," he said.
However, Leboulch is cautious. "This is the first patient in the
trial. Of course we need to do more patients and see what happens,"
Leboulch noted another problem with gene therapy: the inability
to control all the effects a new gene will have in the body. The
globin gene, for example, appears to link to another gene that is
involved in cell growth, causing a mild expansion of blood stem
cells in the patient's body. This could account for some
therapeutic benefits, but might also be a precursor to cancer, the
"So far there is no sign of any abnormality," Leboulch said.
Dr. Francoise Bernaudin, a clinical hematologist who has
followed the patient since early childhood, said it was "wonderful
to see that this young man is for now free of transfusions and
injections for iron chelation.
"He is happy to have a normal life back, and for the first time has a full-time job as a cook in a main restaurant in Paris," said Bernaudin in a news release on behalf of bluebird bio, developer of the LentiGlobin gene therapy treatment that the researchers are using. The trials are sponsored by the Cambridge, Mass.-based bluebird bio.
The report is published in the Sept. 16 issue of
Based on their initial success with gene therapy, Leboulch's
group plans to treat another two patients. If they also respond
well, they will enroll "a larger cohort" of patients, he said.
In addition, the researchers plan to treat patients who have
sickle cell disease with the gene therapy as well, Leboulch said.
The same technique can be used for both diseases, he said.
Leboulch concedes that the treatment is very expensive. But he
hopes that if it becomes widely used, the price will drop,
eventually costing less than a lifetime of monthly transfusions and
Dr. Mustafa Tekin, an associate professor at the John P. Hussman
Institute for Human Genomics at the University of Miami Miller
School of Medicine, said that "gene therapy has been long awaited
"This is the first example of a successful gene therapy for beta-thalassemia," he said. "This brings great hope for patients for the final cure for the disorder."
However, there are possibilities of adverse effects, Tekin said.
He joined the researchers in cautioning that treatment to date has
been limited to just one patient.
Tekin said that the gene that absorbed the therapeutic gene is
associated with certain cancers, such as leukemia. While the
patient does not have signs of the cancer, it is important "to
follow this patient for the long-term for signs of leukemia," he
More trials and patients are needed to really assess the effects
and side effects of the treatment, Tekin said. Whether it will
treat other forms of thalassemia isn't known, he added.
"One patient is important and a significant achievement, but you still need to see more patients to make sure that it works for many patients and also that it works safely," he said.
For more information on thalassemia, visit the
U.S. National Library of Medicine.
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