Joanna Wane looks at New Zealand’s role in a groundbreaking gut-brain axis study that could transform the lives of autistic children.
Five-year-old Charlie* isn’t just a fussy eater. At first, the only way his desperate parents could get anything into his mouth was by spoon-feeding him milk and yoghurt, plus some Weet-Bix for breakfast — until he started refusing to eat the Weet-Bix. Then it got even worse. His grandmother burst into tears one day as she watched this “very sweet, gentle kid” being physically restrained as he fought against every mouthful.
Today, all Charlie consumes is a milkshake-style supplement with the nutrients he needs to survive. “Not only that, but he has to have it in a specific bottle, with a specific straw,” says his father, Alan. “Otherwise he’d just go hungry and starve. He’s one step away from being tube-fed.”
It was Charlie’s refusal to eat solids that first alerted Alan and his wife Erica to the fact that their son was diverging from the normal childhood progression. By the time he was identified as autistic, they had a baby daughter, too.
When the diagnosis was officially confirmed, Alan’s heart dropped. But what he remembers most vividly is the initial consultation with a paediatrician who told them Charlie was “absolutely” on the spectrum.
“His words still sit with me, because he said ‘I’m sorry that you live in New Zealand. I can give you a pamphlet but basically, you’re on your own.’”
Since that day four years ago, Alan and Erica have completely up-ended their lives trying to do the right thing by Charlie. A privately run early intervention programme that seemed to offer some hope wasn’t available where they lived, so Alan quit his job, sold their house and moved the family to a different city.
Over a period of nine months, intensive work with a therapist cost more than $60,000 — fees they paid by cleaning out both their KiwiSaver accounts and borrowing money from Erica’s parents. The difference in Charlie seemed minimal. “His eye contact got better,” says Alan, “but his eye contact progressively got better when we stopped [the treatment] as well.”
The couple chose to protect Charlie’s identity in this story because when it comes to sharing such personal information in the public domain, he’s too young to give consent. The reality is, he may never be able to.
Now in his first year at primary school, Charlie can’t talk, apart from a few simple words. Alan taught him to say “up” when he wants to be bounced on the trampoline, and he can count from 1 to 10 but doesn’t fully articulate the sounds. While he can be affectionate, cuddling up on his mum or dad’s lap and gently stroking their face, the frustration he experiences when trying to communicate is devastating to see.
“It’s really heartbreaking,” says Alan. “We understand a lot of autistic children have aggression issues and outbursts that can be quite violent. That’s not our son. He doesn’t attack or hit anyone. But when he can’t express himself, he’ll scream and he’ll cry and he’ll bang on the desk or whack his knee with his palm. He’ll grab on [to someone or something] and squeeze really hard.”
What worries Alan most is the prospect of Charlie seriously harming himself when he’s in this state. “I’m really quite concerned about that. He’s extremely strong. And sometimes he [accidentally] hurts me, too. I’m a big guy and he’s 5. What does that look like when he’s 15?”
In their search to find more help for Charlie, Alan signed up with a company that keeps them informed of medical trials. That’s how they heard about the Tapestry Autism Study. Only young people aged 13 to 17 who have been diagnosed with autism spectrum disorder (ASD) and experience a clinically assessed level of irritability qualify for the trial, a collaboration between 25 major centres in the United States, Australia and New Zealand. But if the treatment works, it could transform the quality of life for children like Charlie.
When the medical profession talks about “irritability” in autistic kids, it’s not the kind of grumpiness or hormonal mood swings every parent has to deal with on a regular basis. For young people on the spectrum who are struggling to manage their feelings — or who can’t express them — that can erupt into aggression and self-harm, trigger meltdowns or cause them to withdraw, leaving them socially isolated. In extreme cases, the only current option is prescribing antipsychotics.
It’s only comparatively recently that breakthroughs in genetic sequencing have enabled scientists to understand the enormous impact of the gut microbiome on our mental and physical health. James Kinross, a microbiome scientist and surgeon at Imperial College London, calls it the most important scientific discovery for human healthcare in recent decades.
The bacteria in our gut — which is influenced by a complex mix of diet, genetics and environmental factors — produce an array of metabolites that enter the bloodstream and reach the brain. Studies have found that the autistic community tends to have elevated levels of some of these microbial metabolites, compared to those who aren’t on the spectrum.
“People started asking, is this connection just coincidental, is it a consequence of the autism or is it somehow driving the autism?” says Dr Stewart Campbell, CEO of Axial Therapeutics, the US-based biopharmaceutical company behind the Tapestry study.
“What we do know about people with autism is they often have restricted diets that are self-imposed and follow a strict routine. They like certain foods and they only like those certain foods. So it’s the same foods every day, at the same time, which leads to often a less-diverse microbiome. The idea was to try to understand what this so-called gut-brain axis was doing or not doing in the context of behaviour, and how do we build an intervention here.”
Research on mice that were chronically exposed to high levels of the same metabolites found they exhibited many similar symptoms, such as repetitive behaviour, anxiety and impaired communication. MRIs confirmed some of those metabolites had found their way to the brain and revealed connectivity changes in regions associated with emotional processing. In February, a peer-reviewed paper on the findings was published in the British scientific journal, Nature.
What Axial Therapeutics has developed is a molecule called AB-2004, which sponges up the excess metabolites from the gastrointestinal system before they migrate. “So we’re treating something that is having an impact on the brain by targeting something in the gut,” Campbell told Canvas when he and Australian lead Margaret Nelson-Lowe visited the Auckland team at Optimal Clinical Trials, a research centre in Grafton.
An initial pilot study with a small group of autistic adolescents in the US, Australia and New Zealand has already produced promising results. For eight weeks, they were given the drug in powder form, mixed with soft food. Not only did their metabolite levels come down but Campbell says there was a “profound improvement” in irritability and anxiety. “Then when we took the drug away, the metabolite levels went back up and the behaviours started to revert.”
That sounds very dry but for some of the families involved, the transformation was extraordinary. One teenage boy was able to shower on his own for the first time. Another child, a germaphobe who wouldn’t eat anything unless it was prepared in front of him, went to a restaurant with his family and ate a meal he’d ordered off the menu. “Those are the things that I still get emotional about. It made us cry, let alone the parents.”
The gold-standard clinical trials now underway include a placebo group, for true proof of concept. Teenagers are still being sought to take part in the study and the first set of results is expected before the end of next year.
Paediatrician Rebecca Griffith, who’s leading New Zealand’s participation and assesses potential candidates, works part-time in the public health system doing neurodevelopmental and medical follow-ups of premature babies in South Auckland. Pre-term children or babies who suffered a brain injury around the time of their birth are at higher risk of developing conditions including autism. “How amazing would it be to know there’s something that may be able to help with managing some of the difficulties these children experience,” she says.
For autistic people with sensory issues, simply getting dressed in the morning and making it out the door to school or work can seem an insurmountable challenge. “Dealing with anxiety and stress is extremely tiring. For a young person trying to modulate their emotions, it’s that much harder. If you can just take the edge off, they’re going to enjoy their day more and have the capacity to interact with others more, in the same way that we can.”
AB-2004 isn’t a cure for autism, Campbell is clear on that. He describes the goal as turning down the amplifier to a more manageable level. “Neurodiversity is a real thing. We’re all different, right? It’s not about going in to fundamentally change who they are but to address the challenges they face and make their life easier, day to day.”
The principle of using a drug to bind metabolites that are then passed in a stool has been applied before, to reduce toxins in people with chronic kidney disease, for example. However, Campbell believes it’s never been used to treat psychiatric or neurological conditions. The company has another drug candidate heading to clinical trials that aims to slow down the progression of Parkinson’s by blocking a misfiring microbial protein.
An estimated 1 in 54 children in the US has been identified with ASD, according to the Centers for Disease Control and Prevention, a significant increase within the past two decades (it’s also four times more prevalent in boys than in girls). That can be partly explained by better diagnosis, says Campbell, but higher rates in developed countries suggest environmental factors may also be involved.
If the Tapestry study is successful, the next stage would be open to children as young as 5, the age at which irritability can be clinically assessed. So far, the only side effect has been rare cases of constipation.
As far as Autism New Zealand chief executive Dane Dougan is concerned, any evidence-based research is a positive thing. “We’re very happy and excited about it,” he says, speaking for a vulnerable community that’s often targeted by unproven alternative therapies or outright scams. “As an organisation, we’re very careful who we partner with in these spaces because there are a lot of different theories out there and a lot of them don’t have an evidence base.”
Autism NZ runs a number of workshops for families and health or education professionals directly involved with children on the spectrum. Dougan says the focus has moved away from intervention programmes to creating supportive environments that allow autistic children (and adults) to thrive.
Alan, whose personal account opened this story, can only hope the Tapestry study makes a breakthrough. Trying to find the right resources for Charlie is a full-time job — and he and his wife Erica both have full-time jobs of their own. The first primary school they approached told them there wasn’t a place for Charlie, due to his very high needs.
Alan thinks his son would be a perfect fit for the microbiome treatment. After years of struggle trying to access support, Charlie now has government funding for a teacher aide and a “sensory corner” in his classroom where he can play.
There’s a seven-year wait for therapy dogs, so the family is getting a puppy and applying for Lottery Grant funding to cover the $12,000 cost of training her. Alan is also investigating a lockable version of a GPS tracker used for seniors with Alzheimer’s who are prone to wandering. Charlie has twice done a runner, and autistic children are at high risk of drowning because they’re attracted by water but don’t understand the danger.
“What I’ve learned is that you have to fight for absolutely everything,” says Alan. “It’s hard because it takes time and people don’t listen to you and you just keep knocking on doors and it’s exhausting. You’re always feeling guilty because there might have been an opportunity you missed. And you’re constantly beating yourself up and asking, ‘Are we doing enough?’ And you never feel like you are.”
- To find out more about the Tapestry Autism Study and whether a young person might be eligible, visit www.optimalclinicaltrials.com or www.theautismstudy.com
*Names have been changed to protect the family’s privacy.