The first attempt at gene therapy against Parkinson's disease has yielded promising results and is safe, according to early data from a ground-breaking experiment.
The pilot study, conducted among 11 men and one woman in New
York, marks the first-ever use of a "Trojan horse" technique
against the tragic disease.
The technique entails taking a gene and tucking it inside a disabled cold
virus, which is then injected into a key area of the brain. The
harmless virus "infects" the local cells and thus stealthily
delivers the corrective piece of genetic code.
The 12 volunteers, all of whom have advanced Parkinson's, showed
significant improvement in trembling, jerkiness and other symptoms,
and none had any side effects, according to an assessment carried
out a year after the operation.
The paper, appearing Saturday in the British journal The Lancet,
could be an important spur for gene therapy.
In the 1990s, the dramatic rise of biotechnology spurred hopes
of a "new dawn" for medicine in which inherited diseases could be
wiped out by simply replacing the faulty genes in targeted cells
with the right ones.
More complex than thought
But this vision became darkened by setbacks as scientists
gradually realised that an individual's genome is a complex,
interwoven tapestry -and substituting one gene with another can
have far-reaching consequences elsewhere.
In 1999, this frontier research was blighted by the death of an
18-year-old American volunteer, Jesse Gelsinger, whose immune
system ran amok following a gene transplant to fix a liver enzyme
In 2002, French researchers were stunned when three out of 10
children they had cured with corrective genes to fix X-SCID, an
inherited immunodeficiency disorder, suddenly developed leukaemia.
In this climate of deep prudence, researchers led by Matthew
During, a professor at Cornell University's Weill Medical College,
Cornell University, were placed under tight constraints in their
experiment, which aimed primarily at testing for safety.
Parkinson's is an incurable, degenerative disease of the central
nervous system that causes uncontrollable shaking, along with
impaired speech and movement. In approximately one third of cases
it also results in dementia. The disease affects at least one
percent of people over the age of 65.
The cause is a loss of dopamine, a chemical messenger that helps
direct movement. The substance is provided in a part of the brain
called the substantia nigra.
Attempts to treat Parkinson's have focussed essentially on
providing a pharmaceutical substitute for dopamine or on restoring
or protecting dopamine-producing cells.
A different approach
During's team took a different tack, though. They aimed at part
of the brain called the subthalamic nucleus, which becomes
hyperactive as a result of Parkinson's and "blocks" signals to the
nervous system, thus hampering motor control.
Using a magnetic resonance imaging (MRI) scanner to pinpoint
their operations, the team delicately delivered a gene that
controls an enzyme, glutamic acid decarboxylase (GAD), into the
volunteers' subthalamic nucleus.
The idea was to use the gene as a switch to reverse the
subthalamic nucleus' activity, turning it into an inhibitor rather
than exciter of motor output signals.
None of the patients suffered any ill-effects from the surgery,
or from the transplanted gene. Within three months of the
operation, they reported substantial improvements in the side of
the body that was opposite to the brain hemisphere where the gene
was delivered, and the improvement continued until 12 months, the
endpoint of the trial.
The researchers say the results, while preliminary, are
encouraging, especially as US health watchdogs only gave them
cautious authorisation for a gene transplant on one side of the
brain, not both.
But Parkinson's researcher Jon Stoessl of the University of
British Columbia, expressed caution.
The long-term effect of this therapy on the subthalamic nucleus'
role in learning remains unclear, he said in a commentary, also
carried by The Lancet.
Another unknown is whether the virus, even though disabled and
transferred to only a tiny part of the brain, could affect
neighbouring structures, he said.
Finally, there was no proof yet that this technique was any more
effective than tried-and-tested implants to stimulate the
subthalamic nucleus, Stoessl said. – (Sapa-AFP)
Gene therapy – what you should know