'I can walk again'

Judy Hobson on a medical breakthrough that offers hope for
Parkinson's sufferers

Tuesday April 1, 2003
The Guardian

A neurological team working in second world war prefabs at Bristol's
Frenchay hospital has developed a new treatment that is reversing the
distressing effects of Parkinson's disease. The team, led by
consultant neurosurgeon Steven Gill, is the first in the world to
infuse a substance called GDNF directly into patients' brains to
reactivate damaged cells. The five volunteer patients, men aged
between 42 and 62, are continuing to improve.

The symptoms of Parkinson's, first described as the "shaking palsy"
by James Parkinson in 1817, include difficulty walking, tremor,
muscular rigidity, clumsiness and a proneness to falling over. There
are 120,000 sufferers in the UK; the disease affects 1-2% of all
people over 50, and of the 10,000 new cases diagnosed every year, one
in 20 is under 40.

Frenchay hospital is now leading a worldwide study into the use of
GDNF to find the optimum dosage. But the team's work is being
hampered by a shortage of beds to accommodate the trial patients
during the detailed assessment needed to monitor treatment.

All five patients in the pilot study have become more active. One of
them is 64-year-old widower Henry Webb, a retired Welsh miner from
Gwent. "It is unbelievable to see me now when you think of how I was
before the treatment," he says. "I had difficulty walking 50 yards.
Now I go walking, play lawn and indoor bowls and go dancing. I still
have a slight tremor in my right hand, but the best thing of all is
that I sleep a lot better. In fact, you can say I am marvellous."

"What we are seeing is that GDNF has the potential to reverse the
effects of this disease," says Gill. "In patients with Parkinson's,
loss of cells producing dopamine causes their symptoms. GDNF is able
to reactivate and restore these cells and in so doing reverse their
symptoms.

"From scans of their brains, we have found an increase in dopamine
levels in the damaged regions where the GDNF is now being delivered."


He believes the technique is the most exciting development in the
treatment of Parkinson's in years. "The prospect of reversing the
process opens the way for treating a range of neurological conditions
such as Alzheimer's disease, Huntingdon's chorea, motor neurone
disease, stroke and multiple sclerosis."

The GDNF is delivered through a fine catheter implanted into the
brain, which is in turn connected to a pump implanted in the
abdominal wall. The pump is refilled with GDNF on a monthly basis
when the patient is assessed. Gill believes that once the technique
is properly established and scientists have a better understanding of
the activity of the growth factor, the pumps may need refilling only
every three to six months.

GDNF (glial cell-derived neurotrophic factor), obtained from human
protein, is produced by American biotech company Amgen. If further
trials prove successful, Gill says GDNF could become available for
treatment of patients with Parkinson's in three to four years' time.

In the interim, deep-brain stimulation, pioneered in France in the
1980s, is the treatment of choice, but is available to few sufferers
in the UK because there are only a handful of centres that carry out
this surgery. The Frenchay team has pioneered a rapid, safe and
precise method of targeting deep-brain structures under general
anaesthetic - a big step forward from inserting probes to find the
target under local anaesthetic and less distressing for the patient.

Magnetic resonance imaging (MRI) builds up a 3D picture of the brain,
enabling surgeons to perform highly accurate deep-brain stimulation.
Gill, who has operated on 60 patients in this way over the last 18
months, outlines the precision required: "Not only is the target
deeply situated in the brain, it is also very small - between two and
a half and three and a half millimetres in diameter. Misplacement of
the electrode from the target by as little as one to two millimetres
can cause distressing side effects, so a high degree of accuracy is
required."

To identify the target, the team uses high-resolution MRI scans taken
over a long period with the patient under a general anaesthesic. "On
these we can see the small target with sufficient clarity to target
it directly. The first part of the operation involves the
implantation of a plastic guide tube and a plastic probe into the
target using a 3D guidance system. The patient then has another MRI
scan to identify if there is any slight displacement of the probe
from the planned target due to brain movement.

"Once the target has been sufficiently localised, the probe is
removed and a DBS wire is passed down the guide tube into the target.
Being able to see accurately where the DBS is placed is, I believe,
why we have such a low rate of complications. Our patients are able
to leave hospital very quickly - they come in for surgery on the
Friday and go home on Tuesday or Wednesday - because the electrode
ends in the correct place and adjustments of the current settings are
usually minor."

But, says Gill, the team desperately needs money and resources to
continue its research. "We are in a strong position to do stem cell
research, which cannot be done in the US because of legislative
restraints. But we face serious constraints. The first of these is a
critical shortage of beds. Another is the limited MRI scanning time
available to us because the scanner is shared with busy neurosciences
and general hospital services.

"To make the recent advances in functional neurosurgical treatment
more widely available, we urgently need facilities for the education
and training of other neurosurgeons in these complex techniques."

He has drawn up a draft proposal for the building of a centre for
functional neurosurgery, which would cost £3m to build and equip.
"This would solve the critical problems of bed space for trial
patients and would enable us to provide high-quality training.

"Regional health authorities don't have the resources for this kind
of thing. At present we operate out of prefabricated buildings put up
in the 1940s by the Americans for the D-Day troops. Competing with
routine traumas is holding back our clinical research. What we are
desperately looking for now is a philanthropist to give us a proper
building."

For more information, contact the

Parkinson's Disease Society,
215 Vauxhall Bridge Road,
London SW1V 1 EJ,
tel 020-7931 8080;

http://www.parkinsons.org.uk

Donations can be sent to

Diane Cornish,
academic development manager,
Neurosciences Directorate Office,
Frenchay Hospital,
Bristol BS16 1LE.

· Parkinson's awareness week begins on April 6

SOURCE: The Guardian
http://www.guardian.co.uk/health/story/0,3605,926887,00.html

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