NZ hope on Parkinson's

By MARTIN JOHNSTON


A controversial New Zealand scientist who took his skills to the US because he thought his work would be better supported there has won approval to test his potentially revolutionary treatment for Parkinson's disease on humans.

Professor Matt During still works with Auckland University's molecular medicine division but is based at the Jefferson Medical College in Philadelphia.

He left New Zealand in 1998 for Yale University, saying US authorities were more flexible and eager to help his research.

Yesterday, his transpacific team announced a "significant advance" in their technique of inserting a synthetic gene into the brain using an inactivated virus.

Their latest findings, which come after more than a decade's work, were published yesterday in the prestigious journal Science.

In a world first, the United States Food and Drug Administration has approved a trial to test the therapy for safety on 12 people with severe Parkinson's, after promising results in animal trials. The human trial is expected to start within months.

New Zealand sufferers may also be used in trials.

Professor During said he would apply to health authorities here next year to run a trial of the therapy's safety and effectiveness.

About 7000 New Zealanders and millions of others around the world are affected by Parkinson's, a disorder characterised by trembling, rigid posture, slow movements and a shuffling, unbalanced walk. It is caused by the destruction of brain cells that make dopamine, a chemical important for movement.

Sufferers' speech can become slow and hesitant, but their intellect is unaffected until late in the disease.

Well-known sufferers of the degenerative disease include boxing legend Muhammad Ali, American actor Michael J. Fox and New Zealander John Walker, a former world-record holder for the mile.

In a rat trial, Professor During's therapy produced a 75-80 per cent reduction of the tremors, rigidity and slow movement that characterise the disease. There was also evidence it might stop or delay its progression.

"It's not a cure by any means, but I think it's a significant advance," Professor During told the Weekend Herald yesterday.

The therapy will involve boring a small hole in the patient's skull and inserting a drop of liquid, which is made in New Zealand and contains the virus-coated gene.

The surgeon guides it, using techniques including magnetic resonance imaging, to the part of the brain called the subthalmic nucleus, which is extremely overactive in people with Parkinson's.

Professor During said the therapy worked by calming and "resetting" cells that had become overactive. It also seemed to stop the destruction of cells that make dopamine, a message-carrying chemical important in movement.

The gene involved is called GAD, and it makes a substance named GABA, which is released by nerve cells to slow activity.

"We isolate the virus and grow it in the lab, we gut it out, we pull all its DNA out and put our DNA into it ... that is completely safe and may be inserted directly into the brain."

The treatment mirrors surgical therapies that destroy a small area of overactive brain cells or calm them with permanently placed, battery-powered electrodes.

Professor During said that if the new therapy proved beneficial for the 10-15 per cent of Parkinson's patients with severe disease, it could be tried at earlier stages.

Dr Bronwen Connor, of Auckland University's pharmacology division, described the gene therapy as a very exciting and novel development.

Dr Connor, a neuro-scientist who is researching gene therapy separately from Professor During's team, said his experimental therapy brought closer the genetic treatment of other neuro-degenerative disorders, such as motor neuron disease, Alzheimer's and Huntington's.

Professor During drew controversy in New Zealand in 1996 with a gene therapy he developed with his team in the United States.

In a breakthrough operation at Auckland Hospital, surgeons implanted the synthetic genes in the brains of two American infants suffering Canavan disease, a rare and fatal brain disorder.

Ethical debate raged among medical academics, who said the girls' parents had no right to let them be used in an experimental operation.

Professor During was accused of using New Zealand as a "soft touch" because he had been unable to get approval in the US.

But the work gained approval - later upheld by an independent review - from an Auckland ethics committee.

Plans to treat more children were approved in New Zealand, subject to United States regulatory consent.

But in 1998 Professor During returned to Yale University.

Yesterday, he said the bid to run the first human trial of the Parkinson's therapy was made in the US because New Zealand was "nervous about approving trials that have not been done elsewhere".

"It's a sense that New Zealand doesn't really have anyone else except for myself who is actively doing gene therapy in the clinic, so they don't really have the expertise and experience at regulating this.

"Everyone feels more comfortable if a place like the US has reviewed it and says it's okay to move into the clinic."

* Additional reporting: Rebecca Walsh

Further reading
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