Groundbreaking study on zinc for autism

A world-first study is underway at the University of Auckland, testing the effects of zinc on human brain cells grown in the lab.

Auckland Medical Research Foundation granted almost $145,500 to physiology Professor Johanna Montgomery, who is leading the research at the University’s Centre for Brain Research, with support from PhD student Zoe Payne, Professor James Ellis from the University of Toronto, and Dr Kevin Lee from the University of California in San Francisco.

Montgomery has spent the past 15 years looking at links between autism and SHANK genes. These genes are vital for brain cell communication, but some people with autism are born with missing or altered SHANK genes.

For the past 10 years, Montgomery’s team has been looking at the impacts of zinc on SHANK and other genes in the brains of mice.

That research demonstrated that giving zinc to pregnant and lactating mice helps prevent their offspring from showing autistic behaviours, such as anxiety, deficits in social interactions, and repetitive behaviours.

Earlier research by Montgomery’s team showed giving zinc to young mice reversed some symptoms of autism.

“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,” she says.

In some mice, autistic behaviours completely disappeared with zinc treatment, while other mice displayed reduced severity of symptoms, she says.

Montgomery warns it’s too early for people with autism to start taking zinc, which can cause harmful effects at the wrong dosage.

Autism can be caused by numerous factors and not all are associated with the gene variants targeted in the research with mice.

“We don’t yet know the effect of zinc on humans with autism - that’s why we’re carrying out this research on human brain cells.”

Over the years, Montgomery has reached out to families of people with Phelan-McDermid syndrome, a developmental disorder that typically includes autism, severely impaired learning, speech difficulties, gastrointestinal disorders, seizures, and low muscle tone.

The research team has now partnered with those families and will take blood samples from about five people with Phelan-McDermid syndrome, which is caused by the SHANK 3 gene being partially or completely deleted.

The University of Toronto has sent cell samples from people with SHANK 2 gene variants, which are also associated with severe autism, to be used in the experiments.

The blood cells will be “trained” and multiplied in incubators in the lab to become thousands of brain cells, which the scientists can use to research the impacts of zinc.

Electrodes will test how well signals travel between brain cells, before and after the cells receive a dose of zinc.

“We predict there are altered connections between brain cells in people with Phelan-McDermid syndrome and autism.

“Our mouse models showed zinc strengthens communication between brain cells, so we want to see if this is also the case in human brain cells.”

Montgomery is working with a clinical nutritionist, paediatric neurologist and neuropsychologist to design a pilot clinical trial to examine the effects of zinc supplementation on people with Phelan McDermid syndrome.

If funding can be found, the pilot clinical trial will start by exploring the impacts of zinc on the social behaviours and cognitive abilities of people with Phelan McDermid Syndrome, then broaden to include people with severe autism.

Almost one percent of the population in New Zealand is diagnosed with autism, but there is currently no drug treatment available specifically for autism or Phelan-McDermid syndrome, she says.

For some people, autism spectrum disorder is a mild condition that requires no treatment, but for others it causes severe disabilities.

Many children with SHANK gene variants have intellectual disabilities and many parents have to leave work to care for their children full-time, Montgomery says.

“I would love it if this research eventually helps families to experience improvement in their children with Phelan-McDermid syndrome.

“I remember one of the parents saying, ‘I wish one day I could hear my child say Mum’.

“It’s heartbreaking that they haven't had that experience and it would be amazing to find a way to help.”

Previous funding from Auckland Medical Research Foundation and grants from the Health Research Council, Marsden Fund, and Neurological Foundation have paved the way for the current research.