The lives of Parkinson's disease sufferers could be turned around if a new drug developed in Dunedin, and about to be trialled in this country, proves to be a medical breakthrough.
Dunedin, you've done it again. The plucky southern city that keeps trying to get the rest of us to go and live there is at the forefront of a major breakthrough in medical science - a breakthrough that could spell hope for Parkinson's sufferers worldwide. Excitement is high over the prospects for MitoQ, a new drug invented at Otago University, developed and made entirely within New Zealand and about to be trialled here as well.
Neurologist Barry Snow is a Parkinson's specialist. What he doesn't know about Parkinson's isn't worth knowing. Notwithstanding the message you get when you reach the Michael J Fox Foundation in the US ("Hi, I'm Michael J Fox and we're working with scientists round the clock to find a cure for Parkinson's in the next 10 years"), Snow will tell you that no cure is near - that with current knowledge the best we can hope to do is slow down the progress of the disease.
Given all that, MitoQ excites him more than any form of treatment he has ever seen.
"I feel so optimistic about this," says Snow, who is clinical director of Auckland Hospital's neurology department. "I don't know how many patients with Parkinson's I've seen and how many tough times they've had, but if I could give them a drug that would turn them around, that would be the best thing in my career. That would be just fabulous."
Baffled by what causes Parkinson's, experts have tried everything from deep brain stimulation - drilling a hole in the skull and inserting an electric wire - to tissue transplants, skin patches and a pharmacopoeia of drugs with exotic names such as Pergo-lide and Amandatine. But all of these attack the symptoms, not the mechanism that produces the symptoms.
The fundamental mechanical problem is a shortage of dopamine in the substantia nigra, a tiny spot at the point where the spinal column joins the brain. This is part of the body's motor planning area: it sends out the electrochemical messages that make us move our muscles without having to think about it every time. Like adrenalin and serotonin, dopamine is a neurotransmitter, ie, its job is to help pass the messages along. The core characteristic of Parkinson's is a dopamine deficiency.
Consequently, says Snow, "a person with dopamine is as co-ordinated as you and me or as fast as John Walker was, and a person without dopamine slows right down. There are other features, too: stiffness and tremors."
Many of the drugs taken by Parkinson's sufferers seek to put dopamine back into the body, and they can be very effective, says Snow - for a few years, anyway. Other drugs called agonists mimic the body's production of dopamine. But inevitably the disorder gets more complex over time, and the dosage goes up and up, often with negative side-effects.
Only relatively recently has it come to be understood that oxidative stress caused by cell dysfunction disrupts and displaces the natural flow of dopamine. As it happens, the body produces its own powerful antioxidant, CoQ, but with Parkinson's there is not enough CoQ to prevent damage to mitochondria - the fuel cells that metabolise food into the energy that keeps us all going.
Five years ago, Otago University chemistry professor Rob Smith and biologist Mike Murphy hit on a way to get CoQ back into the mitochondria, which is heavily shielded and tends to resist intruders. Their drug (MitoQ) involves phosphonium, phenol and other stuff beyond this writer's grasp, but the key thing is that now, instead of being rejected by the mitochondria, the CoQ gets attracted in, and stays there in very high concentrations.
"This is an enhancement of what we've already got in our body," says Snow, "so it's not surprising that it's extremely well tolerated. That's another major advantage of this treatment - that what we're trying to do is put the person back the way they used to be. We're not putting in a patch-up; we're trying to replace the missing CoQ."
Smith says modestly that he and Murphy, an Irishman now at Britain's Cambridge University but still in constant touch, had an element of luck, in that MitoQ was the first compound they made together.
"We've subsequently made variations on that theme," he says, "and so far none of them have been any better than the one we made originally.
"I guess our uniqueness is in taking this phosphonium business, which had been well established and used at research level, and chemically connecting it to an antioxidant part which is the Q part - so we've got a sort of truck-and-trailer situation."
MitoQ has been tested on animals in England, and they know it's safe on humans, thanks to testing in Christ-church, but now comes the real test: will it slow Parkinson's? A year-long clinical trial involving up to 120 people with Parkinson's will begin soon under the watchful eyes of Snow and 10 other neurologists at the main regional hospitals throughout the country. If successful, it may not get on to the market for at least a year or two after that, pending regulatory approval from all manner of medical and governmental bodies here and overseas.
When it does go on sale, it will be a great day for Ken Taylor, a New Zealander who worked overseas in major drug companies for many years before coming home to found Antipodean Biotechnology, whose sister company Antipodean Pharmaceuticals is dedicated to the making and marketing of MitoQ. Taylor, once a fellow student of Rob Smith's, estimates that about $20 million has been invested in the product so far, mostly by New Zealanders but also by US biotech venture capitalists.
Snow gives Taylor credit for not selling out to some Swiss or German pharmaceutical giant.
"He has always recognised that the skill base is in New Zealand to do something fabulous, which is to invent a drug and take it all the way and make it work. And so Ken has consciously done as much as he could of this in New Zealand. It was invented in Dunedin, made in Wellington and formulated into tablets at Douglas Pharmaceuticals here in West Auckland ... and it's being tested on humans by Richard Robson's group in Christchurch."
Swiss bankrolls may yet be required but, says Snow, "We're going to see how far we can get here before we have to call for help."
Snow, Taylor and Smith clearly believe they're on to something very big here. No one knows for sure yet, but in 18 months' time, says Snow, they will have an answer.
"The answer could be that it doesn't work; the answer could be that it makes a huge difference. It's more likely to be somewhere in between. But remember: if you're going to have a disease for 20 years, even a 25 percent difference can make a huge difference to a person's life. So we'll be delighted at modest improvement - and we'll be ecstatic at a major improvement."
How much improvement is improvement?
"Let me put it this way. When I diagnose a person with Parkinson's disease, I often say to them that with good treatment and care generally, I can keep you in really good shape for five years and pretty good shape for 10 - and then you may remain in a good groove, but there are plenty of people struggling by then. It's hard to see into the future, but [with this drug] I'm hoping that five to 10 years can be made into 10 to 20 years, in which case a person in their sixties could be allowed to enjoy the last years of their work and through into their retirement without struggling with the disease."
As for Marc McNaught - who can't take part in the MitoQ trial because, in his own words, he's "tainted with other drugs" - Snow says it would be huge for him: "If a drug like this worked, we could stop him getting worse. He could carry on working, look after his kids."
Yes, agrees McNaught, "If it works as well as they hope it might work, it'll change my life completely. I don't get my hopes up about it, because you just can't afford to do that."
Former Olympic gold-medallist John Walker, who has had Parkinson's for 15 years, takes a similar view.
"But if it's a big breakthrough," says Walker, "that's tremendous, because somebody out there in the next three or four days is going to be diagnosed with Parkinson's."