The way we approach autism is evolving. That encourages some Calgarians and concerns others

Editor's Note: This story has been updated to include a diversity of perspectives on medical research around autism.

For one Calgary family, learning a rare genetic mutation was the root of their son's severe autism led to a sense of hope.

Mousumee Dutta and Ian Holloway have struggled over the years to make life better for their son.

Ishaan Holloway, 17, was diagnosed with severe autism when he was a young boy. Though he was non-verbal, after taking therapy designed specifically for autistic children, he spoke for the first time in his life when he was 10, using a letterboard.

Epilepsy affects a minority of people with autism. Though he doesn't have full epileptic seizures, Ishaan has frequent sub-clinical seizures. He tells his family, using a keyboard to speak, that he feels like his "brain is on fire," and his family says he is almost always in a state of heightened agitation.

It's for those reasons that the family hopes pinpointing the cause of Ishaan's autism could lead to treatment that would help Ishaan lead a fuller life and bring him closer to his hope of one day living on his own.

Over the years, the family tried various treatments, but Ishaan's condition did not improve. His parents were eager to find out if a genetic mutation was blocking the treatments of his neurological pathways.

"I knew there had to be more," Dutta said.

After hearing about it on Facebook from other parents of autistic children, the family wanted to try whole genome sequencing, which is the study of the entire sequence of one's DNA.

From 2013 up until 2018, the family did not have access to the testing. Ishaan was not eligible for the testing because he was not diagnosed with a syndrome.

But after years of advocating, doctors determined Ishaan had a rare gene mutation. That opened the door to an application for funding for whole genome testing.

To date, more than a hundred mutations have been found to have a direct link with autism and blocking synaptic function that is, transmitting messages between neurons and muscles.

Time and money needed for future research

The family is asking for a second and final stage of the research to determine if drug repurposing can reduce the effects the mutation has on the brain.

"Such research is very expensive, and we don't have that kind of money left," Mousumee said.

The family has spent over $100,000 in tests and treatments. This personalized research alone will cost them $200,000.

This research will determine if existing drugs for syndromes can be repurposed to address the effects of the genetic mutation that Ishaan has.

Steve Scherer, chief researcher at the Hospital for Sick Children in Toronto, said new technology is playing a role.

"Lots of the pharmaceutical companies and biotech now have jumped into the game because they're very good at screening their existing compounds that they have against cells," he said.

"The Holloway family are involved in such studies, and I know that their cells are being turned in the laboratory into what we call stem cells and then turned into brain cells to screen for."

Even though technological advances have sped up the research, "it's essentially a 10-year process, and we're [still] learning more," he said.

Since autism cases are unique, the research is focusing on precision medicine. That means there won't be a single drug or medicine that will impact all of those who have an autism diagnosis.

The conversations we have

Still, any conversation that references searching for a "cure" for autism raises concerns for others.

To them, that sort of language suggests that there is something inherently wrong with the autistic mind, and erases the perspective of those living successfully on the spectrum.

"The idea of a cure means there's something wrong with us," said Bruce Petherick, an autistic advocate with Autism Canada, who has autism himself. "We are just different, and society needs to expand it's not fixing me, it's recognizing the differences and being open to more accommodations, which of course, helps the entire world."

Some families clearly struggle with some of the conditions sometimes brought on by severe autism, including seizures, said Lawrence Fung, director of the Stanford Neurodiversity Project at the Stanford University School of Medicine.

Given that reality, Fung said a balance must be found in our conversations.

"We cannot sugarcoat it and say, seizures can be something good. Because we really need to fix it," Fung said. "We really want to make sure that the person is going to be healthier. But if the same person has a lot of deep interests, for example, that's very good for their development."

Society, according to Fung, is used to viewing autism through a "deficit-based model" focusing on what is wrong with an individual, rather than what they do well.

That's why he's been encouraged in recent years to see various initiatives emerge focused on making neurodiversity a competitive advantage.

After all, it's been speculated that some of modern history's greatest thinkers were likely somewhere on the autism spectrum.

"Say, for example, like Albert Einstein, or Alan Turing, or Nikola Tesla. They all have symptoms of autism," Fung said. "So if they don't really do their obscure examination of what they are interested in, the world will be very different."

Calgary resident Mac Walsh, 20, was diagnosed with autism when they were 14 years old.

Walsh said working with people with disabilities was an interest of theirs since they were about six years old. They are now in school to be an education assistant to help other kids in the same situation.

"I think the more people understand and accept that the way someone with autism, that their brain works differently it's not always a disadvantage, but can be an advantage. It's a really important piece of understanding," Walsh said.

Pushing for answers

The Holloway family, meanwhile, agrees that society should be more accepting of neurodiversity but say those who are on the severe end of the spectrum are living with a more challenging reality.

It's for that reason they say they will continue to push for continued research for those individuals.

The broader project of research around this subject, dubbed the MSSNG project, has collected data from more than 12,000 families, including the Holloway family.

It uses whole genome sequencing to build a database on autism with deep phenotyping.

The project is a collaboration between the Hospital for Sick Children, University of Toronto, Autism Speaks, Verily and DNAstacks.

The project, and one of those organizations, Autism Speaks, are controversial in the autism community. The project's chief science officer Tom Frazier pushed back on what he called misconceptions of the project in an interview with Newsweek in 2021.

"There's this sort of misconception that somehow the MSSNG Project is about finding an autism gene and then doing gene therapy to get rid of autism. That is a very, very bad misconception, I would say, of the project," Frazier said.

"The project really is about actually trying to understand the biology of people with autism so that we can identify the kinds of interventions and supports that they might need."

The database is available only to certified researchers to develop personalized treatments.

"We think that 90 per cent of why autism comes about has to do with genetic factors," said Scherer, the chief researcher at the Hospital for Sick Children.

This project is the only one of its kind in the world. It has found that in 20 per cent of the participants, the mutation was the root cause of autism.

Once the study shows the family has hit one of the listed genetic conditions, they are provided the information through a genetic counsellor to predict the behavioural trajectory and appropriate interventions to treat it. It also predicts the chance another child in the family will have autism.

Dutta reached out to hundreds of doctors, including Nobel laureate Thomas Sdhof. He responded to her email and encouraged the family to move forward with the research.

Dr. Soham Chanda, one of Sdhof's former students, agreed to include Ishaan's genetic mutation in his study on the impact of how it blocks amino acids.

He is an assistant professor at Colorado State University who started a lab with a team of researchers to carry out the first stage of the intensive research on the effects of genetic mutations on our neurological pathways.

In his 2019 study, Chanda was able to identify some amino acids that were blocked by the mutation, which led to behavioural issues like hyperactivity and secretion of acids.

"We were super happy to know why Ishaan has this type of autism. If somehow we can unblock this with treatment there is hope," Dutta said.

Still, the family is anxious for answers and are hopeful that the research can go on to help others, too.

"We are doing this not just for our son. But if this is successful, many parents will be able to help children on the severe end of the spectrum."