First-ever gene therapy for treating Alzheimer's
San Diego researcher tells of positive results with a few patients in
report to S.F. meeting
Carl T. Hall, Chronicle Science Writer
Wednesday, April 28, 2004
Despite some early disasters, a novel gene-therapy treatment for
Alzheimer's disease has produced encouraging results in the first
half-dozen patients, scientists reported Tuesday.
After years of animal studies, researchers led by Dr. Mark Tuszynski, a
neuroscientist and neurologist at UC San Diego, began the first human
safety trial of the new approach in April 2001. Tuszynski summarized the
results during the annual meeting of the American Academy of Neurology,
which is under way this week in San Francisco.
The study has drawn attention as the first attempt to use gene therapy
to treat an incurable neurodegenerative disorder. Alzheimer's disease
currently affects about 4 million people in the United States, and that
number is growing as the population ages.
Gene therapy has been touted as a way of curing some of the most
intractable diseases known, typically by injecting a benign virus or
other "vector" to deliver therapeutic genes inside a patient's own
cells. But the first studies were fraught with safety problems that
cooled some of the early enthusiasm.
In the Alzheimer's study, the idea was to increase the output of a
natural protective substance called nerve growth factor in a
thumbnail-size region of the brain, from which a critical type of nerve
cell sends projections throughout the cortex. Those cells have been
shown to die off in Alzheimer's cases, contributing to the profound
memory loss and confusion that are hallmarks of the disease.
The scientists took skin cells from each patient, modified the cells
genetically so they would secrete the nerve growth factor, then injected
the cells into holes drilled into the patients' heads. Eight patients
were enrolled in the study, which was designed only to establish whether
the elaborate method could be safely tried in humans.
Two patients suffered brain hemorrhages from injuries incurred during
the implantation surgery, Tuszynski said, leading to the death of one
person five weeks after the procedure. The other patient recovered.
Patients initially were kept awake during the surgery, as is often the
case in neurosurgery. The accidents happened when the patients moved
their heads at a critical time, Tuszynski said.
That forced a change in procedures so that the other study participants
were put under anesthesia and immobilized, which prevented more
The trial produced no evidence of any safety problems involving the
altered cells or the nerve growth factor, which can produce powerful
toxic effects if overabundant in the wrong brain regions.
Nor did the injection cure anyone's disease. On standard neurological
tests, the six patients showed a marked slowdown in the rate of
cognitive decline typical for an Alzheimer's patient. Also, an autopsy
of the patient who died showed the injected cells functioned as hoped --
Tuszynski likened them Tuesday to "biological pumps" implanted in the
"This is the kind of results you like to see in a Phase 1 safety trial,"
But the apparent benefits could just be the result of chance -- or the
wishful thinking of the researchers.
The experiment included none of the standard controls researchers must
use in trials designed to prove that a treatment truly works. Two of the
scientists, including Tuszynski, are co-founders of a San Diego
biotechnology firm, Ceregene Inc., which holds a commercial stake in the
The planned next step will be another six-month safety trial of a
modified approach, in which the critical genes are to be injected
directly into the brains of patients, eliminating the need for using the
doctored skin cells. Assuming that study reveals no new safety concerns,
the first true test of efficacy could begin in about 30 patients,
including sham surgeries and other experimental controls. Those patients
are expected to be tracked for about two years.
E-mail Carl Hall at email@example.com.