We don't yet know the effect of zinc on humans with autism
At the University of Auckland, neuroscientist Johanna Montgomery is asking whether a mineral found in everyday food might hold the key to repairing the broken conversations between brain cells in people with autism. Built on fifteen years of genetic research and striking results in mice — where zinc both prevented and partially reversed autistic behaviors — this world-first study now turns to human brain cells, seeking to know whether what is true in animals might also be true in us. For families living with Phelan-McDermid syndrome and severe autism, conditions for which no targeted drug yet exists, the question is not merely scientific.
- Zinc supplementation in mice didn't just ease autistic behaviors — in some cases it reversed them entirely, creating urgent momentum to test whether human biology responds the same way.
- Families of children with SHANK gene variants face a daily reality of intellectual disability and full-time caregiving, with some parents forced to leave work — the human cost pressing hard against the slow pace of science.
- Researchers are transforming donated blood cells into functioning brain cells in the lab, then using electrodes to measure whether zinc can strengthen the weak neural connections caused by altered SHANK genes.
- A pilot clinical trial targeting social behavior and cognition in people with Phelan-McDermid syndrome is already on the horizon, with ambitions to extend findings to broader autism populations.
- The study sits at a fragile but hopeful threshold — mouse models were promising, human cells are next, and the distance between those two facts is exactly what this research is designed to cross.
At the University of Auckland's Centre for Brain Research, Johanna Montgomery is leading a study that has never been attempted before: testing whether zinc can restore healthy communication between brain cells in people with autism. The work draws on fifteen years of research into SHANK genes — the genetic instructions that allow neurons to connect — and a series of compelling results in mice.
In those animal studies, zinc supplementation given to pregnant and nursing mice prevented their offspring from developing autistic behaviors including anxiety, social withdrawal, and repetitive actions. More remarkably, young mice already displaying these traits showed significant improvement after receiving zinc, with some recovering completely. The effect was most powerful during fetal brain development but persisted even after weaning.
Montgomery is measured about what this means for humans. To find out, her team — working with partners at the University of Toronto and UC San Francisco — has begun recruiting families of people with Phelan-McDermid syndrome, a rare condition caused by deletion of the SHANK 3 gene that brings severe intellectual disability, speech difficulties, seizures, and autism. Blood samples from these donors, along with cell samples from people carrying SHANK 2 variants linked to severe autism, will be cultivated in incubators into thousands of functioning brain cells. Electrodes will then measure how well signals travel between neurons before and after zinc treatment.
Montgomery's hypothesis is that altered SHANK genes create weak neural connections, and that zinc can strengthen them. If the lab results confirm what the mouse studies suggested, a pilot clinical trial will follow, examining zinc's effects on social behavior and cognition — first in people with Phelan-McDermid syndrome, then potentially across broader autism populations.
The stakes are real. Nearly one percent of New Zealanders carry an autism diagnosis, and for those with SHANK gene variants, the condition is often severe enough to require full-time parental care. No drug currently exists that targets autism or Phelan-McDermid syndrome directly. For families who have long been without options, the possibility that a common mineral might repair the brain's wiring is a question worth every careful step it takes to answer.
At the University of Auckland's Centre for Brain Research, Johanna Montgomery and her team are running an experiment that has never been attempted before: testing whether zinc can repair the way brain cells talk to each other in people with autism. The work builds on fifteen years of Montgomery's investigation into SHANK genes—the genetic instructions that allow neurons to communicate—and a series of striking results in mice that suggest zinc might do something remarkable.
Zinc is a mineral the body needs for hundreds of functions: immune defense, wound healing, DNA production, growth. Because the body cannot stockpile it, zinc must come from food regularly. When intake falls short or absorption fails, deficiency sets in. What Montgomery discovered over the past decade was that some people with autism are born with SHANK genes that are missing or altered, and that giving zinc to pregnant and nursing mice prevented their offspring from developing autistic behaviors—anxiety, social withdrawal, repetitive actions. Even more striking: when young mice already showing autistic traits received zinc, some of them recovered completely. Others saw their symptoms ease. The effect was strongest during the critical window when the fetal brain was wiring itself, but it persisted even after the mice were weaned.
Yet Montgomery is careful. "We don't yet know the effect of zinc on humans with autism," she says. That caution is why this new study exists. Working with colleagues at the University of Toronto and the University of California in San Francisco, along with PhD student Zoe Payne, Montgomery's team has begun recruiting families of people with Phelan-McDermid syndrome—a rare developmental disorder caused by deletion of the SHANK 3 gene. The condition brings severe intellectual disability, speech difficulties, seizures, and gastrointestinal problems alongside autism. About five people with Phelan-McDermid syndrome will donate blood samples. Toronto has also sent cell samples from people carrying SHANK 2 variants linked to severe autism.
In the lab, these blood cells will be transformed. Scientists will "train" them in incubators, multiplying them into thousands of functioning brain cells. Then comes the measurement: electrodes will record how well signals travel between neurons before and after the cells receive zinc. Montgomery's hypothesis is direct—the altered SHANK genes create weak connections between brain cells, and zinc strengthens those connections. The mouse work suggested this was true. Now she wants to see if human brain cells behave the same way.
If the lab results hold, Montgomery plans to launch a pilot clinical trial examining zinc's effects on social behavior and cognitive ability in people with Phelan-McDermid syndrome, with plans to expand to people with severe autism more broadly. This matters because there is currently no drug treatment designed specifically for autism or Phelan-McDermid syndrome. Almost one percent of New Zealand's population carries an autism diagnosis, but for many—especially those with SHANK gene variants—the condition is severe. Children with these variants often have intellectual disabilities that require full-time parental care. Some parents have had to leave work entirely to manage their children's needs. Montgomery's hope is direct and human: "I would love it if this research eventually helps families to experience improvement in their children with Phelan-McDermid syndrome." The study is still in its early stages, but the question it asks—whether a simple mineral might repair the brain's wiring—has already captured the attention of families who have few other options.
Notable Quotes
Zinc clearly has an effect during the brain-wiring period when the foetus is developing, but perhaps more importantly it had beneficial effects when supplementation was given after the mice were weaned.— Johanna Montgomery, University of Auckland
I would love it if this research eventually helps families to experience improvement in their children with Phelan-McDermid syndrome.— Johanna Montgomery
The Hearth Conversation Another angle on the story
Why focus on zinc specifically? There must be hundreds of minerals and compounds that affect the brain.
Montgomery spent fifteen years studying SHANK genes before zinc entered the picture. The connection came from the mouse work—when she gave zinc to pregnant mice with altered SHANK genes, their offspring didn't develop autistic behaviors. That's not random. It suggested zinc was doing something specific to how those genes function.
But mice aren't humans. Why should we believe this will work in people?
That's exactly why they're doing this study. The mouse results were compelling enough to justify testing on human brain cells. If it works in human neurons the same way it worked in mice, then you have real evidence. If it doesn't, they'll know this particular path doesn't translate.
What happens if the lab results are positive? Do people just start taking zinc supplements?
No. Montgomery was explicit about that—zinc can cause harm at the wrong dose. If the cells show promise, the next step is a careful pilot trial with actual patients, measuring not just whether symptoms improve but how, and at what dose, and for whom. It's methodical.
Why Phelan-McDermid syndrome specifically? Why not just study autism broadly?
Because Phelan-McDermid is caused by a specific, known genetic deletion—SHANK 3. That clarity matters. If zinc helps people with that one genetic cause, it proves the mechanism works. Then you can ask whether it helps other autism cases caused by different genes. You start where the biology is clearest.
How many people are we talking about here? Is this a rare condition?
Phelan-McDermid is rare, yes. But the broader point is that many children with SHANK gene variants have severe intellectual disabilities. Some parents have had to leave work to care for them full-time. If zinc could improve social behavior or cognitive function in even a subset of those families, that changes lives.
What's the timeline? When would people actually know if this works?
The lab work is happening now. If those results are promising, a pilot trial could begin within a year or two. But clinical trials move slowly—they have to, for safety. Real answers probably won't come for several years.