Neurologist Chris Shaw says he believes gene therapy could slow or even halt the onset on motor neurone disease. Photo / Mark Mitchell
Neurologist Chris Shaw says he believes gene therapy could slow or even halt the onset on motor neurone disease. Photo / Mark Mitchell
Working in a laboratory at Cambridge University, New Zealand neurologist Chris Shaw met two patients who changed the course of his career.
The two women had an inherited form of motor neurone disease, and had spent most of their lives waiting for symptoms to appear.
"If you're from a family like this, and you're at risk, then these people spend much of their late childhood or early adulthood waiting for this to happen," Shaw said.
"So every time they trip on the pavement, or have trouble opening a door, they think, oh, is that it? Has it started?"
He has never forgotten the sense of doom which pervaded their lives. To make matters worse, the women knew the next generation would inherit the disease. He promised them at the time - in the mid-1990s - that he would dedicate his career to finding a cure for their children.
Now a neurologist at King's College in London, Shaw is working at the cutting edge of his field. He is seeking approval to correct motor neurone disease patients' defective genes by delivering a virus directly into their brain.
"Yeah it's radical," he told the Herald. "But not wildly crazy."
Shaw's imaginative approach and determination has led him to world-leading discoveries in genetics. It has also won him significant backing: during the pandemic he raised no less than US$100 million ($167m) to trial innovative new treatments for brain disorders.
In a coup for the University of Auckland, Shaw is now bringing his skills - and his fundraising clout - back home. He will today be announced as the new Hugh Green Chair in Translation Neurology at the Centre for Brain Research.
These disorders can be complex to diagnose and more difficult to treat. The centre hopes to translate its scientific developments into new treatments for people with brain disease. Shaw's appointment would "turbo charge" that work, said the centre's director Sir Richard Faull.
"You do brain research to understand the brain better. But if you can take treatments to people and slow or even stop the progression of the disease, that is the ultimate," Faull said.
Sir Richard Faull, director at the Centre for Brain Research, said Shaw's appointment would "turbo charge" efforts to turn research into treatments. Photo / Mike Scott
Motor neurons are responsible for the brain communicating with muscles to create movement. When someone has motor neurone disease, the brain gradually stops being able to send signals to these muscles, which then weaken and waste away. The patient becomes progressively paralysed, can no longer do daily tasks like going to the toilet, then lose their ability to speak and eventually to breathe.
Since that initial meeting with the two women 30 years ago, Shaw has met thousands of patients who have contributed blood, skin and even their brains to his research. His team at King's College has set about identifying many of the genes associated with the condition.
Helped by international breakthroughs, his team can now identify the genetic cause in 70 per cent of families affected by motor neurone disease. But despite this progress, there are still no effective therapies for the disease.
Disillusioned by the failure of pharmaceutical treatments, Shaw's great hope lies in gene therapy. The radical treatment involves correcting a patient's malfunctioning genes - either by muting toxic genes in the brain or by supplementing missing ones.
Now that they have detected the defective genes, the major hurdle is in the delivery. Viruses which carry the corrective genes can be injected into the bloodstream or spinal fluid, but very little reaches the brain and it can leak into other parts of the body.
Shaw believes he may have a solution: inject the virus directly into the brain.
This approach was first trialled in mice, then sheep and monkeys, with increasingly promising results. Shaw will seek approval from British, European and US medical authorities for human trials to treat dementia and motor neurone disease. Investors have backed him to do so - to the tune of US$100m ($167m).
Gene therapy is not without controversy. Patients have died in clinical trials for other disorders. But the inevitability of death is so strong for patients with motor neurone disease that and they and their families are willing to try experimental therapies if there is a chance of major benefit. The impact of existing treatments was relatively modest, Shaw said.
All of which brings him to New Zealand. As it happens, this country has one of the highest rates of motor neurone disease in the world.
Shaw said New Zealand has been "punching above its weight" in neuroscience and gene therapy. He plans to develop and test gene therapies by recruiting and training local scientists, while maintaining his links with King's College and his start-up AviadoBio.
"Hand on heart, I believe if you can correct the genes in this way, you have a real chance of stopping the disease. Not just, you know, a 20 per cent improvement in survival."
