Neurologist Chris Shaw believes gene therapy could slow or even stop the onset of motor neuron disease. Photo / Mark Mitchell
New Zealand neurologist Chris Shaw worked in a lab at Cambridge University and met two patients who changed the course of his career.
The two women had an inherited form of motor neuron disease and had spent most of their lives waiting for symptoms to appear.
“If you come from a family like that and you’re at risk, those people spend a lot of their late childhood or early adulthood waiting for that to happen,” Shaw said.
“So every time they trip on the sidewalk or have trouble opening a door, they’re like, oh, is this it? Has it started?
He never forgot the sense of doom that pervaded her life. To make matters worse, the women knew that the next generation would inherit the disease. He promised them back then – in the mid-1990s – that he would devote his career to finding a cure for their children.
A neurologist at King’s College London, Shaw works at the forefront of his field. He is seeking approval to correct the defective genes of motor neuron disease patients by delivering a virus directly into their brains.
“Yes, it’s radical,” he told the Herald. “But not wildly crazy.”
Shaw’s imaginative approach and determination have led him to world-leading discoveries in genetics. It’s also garnered him significant support: He’s raised no less than $100 million ($167 million) during the pandemic to test innovative new treatments for brain diseases.
Now, in a coup for the University of Auckland, Shaw is bringing his skills – and his fundraising clout – back home. He is announced today as the new Hugh Green Chair in Translational Neurology at the Center for Brain Research.
The center is known for its treasure trove of 1,000 donated human brains used to unravel neurological disorders like Alzheimer’s and Parkinson’s.
These disorders can be complex to diagnose and more difficult to treat. The center hopes to translate its scientific developments into new treatments for people with brain disorders. Shaw’s appointment would “supercharge” that work, said the center’s director, Sir Richard Faull.
“You do brain research to better understand the brain. But if you can treat people and slow or even stop the progression of the disease, that’s the ultimate,” Faull said.
Motor neurons are responsible for allowing the brain to communicate with muscles to create movement. When someone has motor neuron disease, the brain gradually stops sending signals to these muscles, which then weaken and atrophy. The patient becomes increasingly paralyzed, unable to perform everyday tasks such as going to the toilet, then loses the ability to speak and eventually to breathe.
Since that first 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 out to identify many of the genes linked to the condition.
Supported by international breakthroughs, his team can now identify the genetic cause in 70 percent of families affected by motor neuron disease. Despite these advances, there are still no effective treatments for the disease.
Disillusioned with the failure of pharmaceutical treatments, Shaw’s great hope lies in gene therapy. The radical treatment consists of correcting a patient’s faulty genes—either by silencing toxic genes in the brain or by adding missing genes.
Now that they’ve discovered the defective genes, the biggest hurdle lies in delivery. Viruses carrying the corrective genes can be injected into the bloodstream or spinal fluid, but very little reaches the brain and can travel to other parts of the body.
Shaw thinks he has a solution: inject the virus directly into the brain.
This approach was first tried in mice, then in sheep and monkeys, with increasingly promising results. Shaw will seek approval from the UK, European and US medical authorities for human trials for the treatment of dementia and motor neuron disease. Investors have backed him with $100 million ($167 million).
Gene therapy is not without controversy. Patients have died in clinical trials for other conditions. But the inevitability of death is so strong for patients with motor neuron disease that they and their families are willing to try experimental therapies if there’s a chance of major benefit. The effects of existing treatments are relatively modest, Shaw said.
All this leads him to New Zealand. Coincidentally, this country has one of the highest rates of motor neuron disease in the world.
Shaw said New Zealand had “beat over its weight” in the fields of neuroscience and gene therapy. He plans to develop and test gene therapies by recruiting and training local scientists while maintaining his ties to 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 percent improvement in survival.”