First human test of new Parkinson's treatment

By MARTIN JOHNSTON

An American with severe Parkinson's disease will on Monday be the first person to have brain surgery with a promising gene therapy developed by a New Zealand-United States team.

The brain of the 55-year-old television producer from Long Island will receive several drops of the liquid therapy at New York Hospital.

It contains a gene to calm certain brain cells whose overactivity produce the disease's symptoms.

In animal trials it also appeared to halt the destruction of the nerve cells that make dopamine - the process that causes Parkinson's. Dopamine is a message-carrying chemical important for movement.

The research leader, Professor Matthew During, who divides his time between Auckland University and New York's Columbia University, said he was optimistic the treatment would help reduce the man's symptoms.

"It takes about a month for the gene to turn on. That's when we would expect to see some benefit."

Parkinson's, a progressive disease, affects about 7000 New Zealanders. It is characterised by trembling, rigid posture, slow movements and a shuffling, unbalanced gait. It is caused by the loss of dopamine-making cells.

The New York trial will involve 12 people with severe Parkinson's for whom current therapies have stopped working.

It follows promising tests on rats, in which the treatment produced a 75 to 80 per cent reduction of symptoms. There was also evidence it might stop or delay the disease's progression.

Professor During's plan to give the treatment to some New Zealanders has received a setback, but he still hopes part of a yet-to-be-approved second trial can be run in the country. It could start in 2005.

The liquid therapy was being made at his team's Auckland laboratory until the Health Ministry ordered a halt after the US Food and Drug Administration approved its trial use in humans. Now only the bulk material was made at Auckland and it had to be purified in the US.

He said the ministry threatened prosecution if his laboratory made the therapy for human use without a drug manufacturing licence, even though it was only a trial. The FDA required such a licence only for commercial production.

"The laws here are somewhat draconian. People are more risk-averse," said Professor During, known for pushing boundaries.

In 1996 he was criticised over breakthrough, experimental Auckland Hospital operations that treated two American infants with Canavan disease, a rare and fatal brain disorder, using synthetic genes he and his US team had developed. The work was later approved by an Auckland ethics committee.

Ministry senior medical adviser Dr Stewart Jessamine said New Zealand adopted international guidelines on medicine manufacturing last year. They stipulated that clinical-trial medicines must be made in licensed facilities.

On Monday, neuro-surgeons will deliver the therapy to the Parkinson's patient's sub-thalamic nucleus, a walnut-sized part of the brain extremely overactive in people with the disease.

The man, who will be under local anaesthetic, will have a small hole bored in his head. A hollow needle will be guided to the exact spot by magnetic resonance imaging and by monitoring the electrical impulses that vary around the brain. The electrical probe will be withdrawn from the needle and replaced by a catheter to convey the tiny amount of liquid.

It will carry several billion particles of a safe virus each containing a gene called GAD. The gene makes molecules of GABA - a substance released by nerve cells to calm overactivity in the brain - which restores greater control of body movement.

Professor During said the treatment promised a significant advance, but was not a cure.

It mirrored another, more-invasive therapy, which calmed overactive cells through a battery-powered electrode surgically implanted in the brain. But at US$25,000 ($42,450) the gene surgery cost less than half as much.