Researchers unveil largest autism brain map

There are more than 250 genes associated with autism spectrum disorder, and as a result, finding a treatment that targets the genetic source of the disorder has been difficult.

Matthew State, a psychiatrist at the University of California, San Francisco (UCSF) and an author on the new study, said it was painfully clear scientists needed a much deeper understanding of what genetic mutations actually do to the brain before they can hope to create any drugs that treat autism.

"There's a huge missing step," State said. "What the genes are doing is they're building proteins that are driving the biology of the cell."

In order to build the brain map, which was published in Science, researchers from UCSF mapped out how genetic mutations tied to autism could influence interactions between proteins in the brain and found over 1,800 interactions tied to autism, among which 87% had never been seen before.

The researchers developed the map in the presence of the mutations to understand how the proteins were "rewired." Then, they utilized an AI system called AlphaFold to prioritize key mutations so they could be studied in brain organoids grown in a lab.

"AI is allowing us to study proteins that we could never have even dreamed of even a couple of years ago, and it's providing an unprecedented light being shone on autism, the underlying biology behind autism," said Nevan Krogan, an author on the study, professor at UCSF, and senior investigator at the nonprofit Gladstone Institutes.

"The hope would be at some point you'd be looking back and saying, 'Ah, this map led to X, Y, and Z, and therefore we have now the first-ever treatment to autism,'" Krogan added. "That's the vision, and I believe that's going to come to fruition at some point in the future."

Fikri Birey, assistant professor in the department of human genetics at Emory University School of Medicine who was not involved in the study, said the new research "is really exciting in that it represents the most systematic protein-level view of autism risk we've had to date."

"In the future, it may be possible to identify drugs that stabilize disrupted protein complexes or block pathological interactions, rather than trying to correct every individual autism-causing mutation," Birey said, adding that the new findings could help inform the disease-modeling research his lab conducts.

While vaccines are not mentioned in the committee's strategic plan, multiple IACC members at the meeting last week pointed to vaccines as a potential cause of autism.

"We don't want to close the door for any potential trigger, and that would include things like glutamate or aspirin, or a vaccination," said Laura Cellini, founder and CEO of Elucidate ASD, a nonprofit pushing for more medical treatments for autism. "We are quite open to investigating anything and everything. This plan closes no door."

Greg Robinson, director of public policy at the Autistic Self Advocacy Network, who is autistic, said the fact that no one on IACC challenged statements related to vaccines and autism is a sign that a new normal has been established on the committee.

"We are seeing right now the harms that come from misinformation around vaccines," Robinson said. "We know how it has led to promoting harmful ideas about autistic people, about autism, and about supposed cures or remedies for autism for autistic folks that have been harmful or even deadly in the past."

Some researchers and advocates were excited about the committee's desire to alleviate co-occurring conditions like epilepsy and sleep. Meanwhile, others are excited about the shift away from genetics as the main tool to understand both autism and autistic people.

However, some experts said the bad in the plan outweighed the good. For example, the plan gives significant attention to the loss of early language skills and social engagement — sometimes referred to as regression — and suggests there are some immunological, metabolic, or infectious causes behind regression that have yet to be discovered. The plan also devotes significant attention to folate-based therapies like leucovorin despite an overwhelming lack of scientific evidence for their efficacy.

Robinson said he found it concerning the plan didn't address helping autistic adults secure employment or live independently.

"A lot of the life course recommendations that they have … are really pushing away from models that have really maximized our ability to be part of our communities," he said.

Ultimately, the committee voted to officially adopt the plan, with 26 yes votes, one no, and 13 abstentions.