Jake’s Mice: Finding Answers to the Autism Puzzle

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ST. LOUIS (AP) – Jake Litvag leaned in for a closer look as a lab mouse scurried around an enclosure,…

ST. LOUIS (AP) – Jake Litvag leaned in to take a closer look as a lab mouse scurried around an enclosure, stopping to sniff a large block.

“Hello, Jakob 1. My name is Jake,” the 16-year-old said, naming the little furry creature designed to have the same genetic defect as him.

This mouse and its lab-grown parents are the first in the world to reflect the missing gene that causes Jake’s autism. Scientists at Washington University in St. Louis bred mice and cultivated stem cells derived from Jake’s blood, to study and find ways to treat his rare disease – and search for answers to the world’s biggest puzzle. ‘autism.

Jake’s family raised money for the first research, which the scientists then turned into a $ 4 million grant from the National Institutes of Health to investigate the gene for Jake, one of more than 100 people involved in the ‘autism. They hope to find “focal points” that could one day help people with all forms of neurodevelopmental disorders affecting one in 44 American children.

Jake knows he inspired their work. And it has helped him see autism as something to be proud of rather than something that makes him different from other kids. His parents, Joe and Lisa Litvag, believed meeting the scientists – and the mice – would show him firsthand what he had created.

“Oh wow. Cool!” Jake said as he watched a mouse descend from a pole as others scampered into a trash can.

As she walked out of the lab, tears welled from Lisa Litvag’s eyes as she thought about the tongue in her son’s cells helping other children.

“We are deeply proud and touched to be a part of this,” said Joe Litvag. “Why are we living this life? It is ultimately to try, in some way, in a form or in a form, to be of service to others.

GIFT FROM JAKE

The Litvags realized early on that Jake was not reaching the milestones of his childhood. He could not walk without help until he was 4 years old. He had a hard time stringing together sentences in the first year.

At first, no one knew why. Jake had a mixture of different traits. He was hyperactive and impulsive but also social, warm and funny. It took until the age of 5 to get a firm diagnosis of autism.

Around this time, the Litvags heard that child psychiatrist Dr. John Constantino, an expert in the genetic foundations of autism, was giving a talk at the Saint Louis Science Center. They decided to go there in the hope of meeting him. They did, and he started to see Jake as a patient.

About five years later, Constantino offered genetic testing. He revealed the missing copy of the MYT1L gene, which is believed to cause one in 10,000 to 50,000 cases of autism. Having an extra copy can cause schizophrenia.

The discovery brought peace to the family. They had heard many people say that autism was mainly caused by external factors, such as birth trauma. “For a long time,” said Lisa Litvag, “I thought it was something I had done.”

In fact, a large multinational study suggests that up to 80% of the risk of autism can be attributed to hereditary genes.

“One of the great things it has done for us as a family is that it has made us realize that we haven’t done anything wrong,” said Joe Litvag. “It’s just that people are born all the time” with genetic differences.

The couple, whose youngest son Jordan does not have the disease, spoke openly with Jake about his autism and tried to boost his self-esteem when he feared he would be seen as different. They sent him to a small private school which tailors its curriculum to each child’s learning abilities. And they encouraged his social tendencies, cheering him on when he and a few classmates formed a group, the Snakes.

“We never wanted him to feel shame around his diagnosis,” said Lisa Litvag. “We continued to kind of reinforce that this is a super power, you are special, you are awesome… and because you are autistic there are some gifts that you need to give to others.”

FLOWER GIFTS

When Constantino suggested studying the little understood MYT1L gene, the Litvags enthusiastically agreed to help. Constantino – who sits on the local board of a group they’ve been active in for a long time called Autism Speaks – asked if they would be interested in raising money for early research.

Joe Litvag, an executive in the live music industry, and Lisa Litvag, a marketing company partner, reached out to family and friends and raised the $ 70,000 needed in about six months.

With half the money, researcher Kristen Kroll and her team reprogrammed cells in Jake’s blood into “induced pluripotent stem cells,” which can be tricked into different types of cells. Along with the other half, scientist Joseph Dougherty and his team followed Jake’s genome model and induced his mutation in mice using the CRISPR gene editing tool.

Like the people they’re supposed to model, mice with the mutation tended to be more hyperactive than their siblings without it, running around their cages much more. They were, however, generally heavier, especially the first generation of mice. They had a slightly smaller brain and a little less white matter which speeds up communication between different regions of the brain.

Since research began about three years ago, scientists have bred around 100 mice with the Jake mutation and are now using the great-great-grandchildren of the first one they conceived. They recently published on mice in the journal Neuron.

While scientists can’t go back and see how Jake’s brain developed, Dougherty said, mice allow them to watch the mutation unfold through generations.

A RETURN GIFT

Dougherty and his colleagues hope that what they learn about how MYT1L works ultimately leads to drugs or gene therapies that improve or even correct the problems caused by the mutation.

They share their findings with scientists who are studying other genes responsible for autism or trying to understand how various genes work together to cause the disease. According to the Simons Foundation’s Autism Research Initiative, more than 100 genes have strong evidence linking them to autism, and a growing list contains several hundred more genes that are believed to be linked to the disease.

In cases where autism is caused by a single gene, Dougherty said that gene likely does a lot for brain development. One key to understanding autism as a whole is finding a thing or two that are shared between different forms of autism – which could then be targets for treatment. While not all people with autism want treatment, Dougherty said it could help those who do.

Since the research began, Dougherty has written notes to the Litvags explaining the latest findings. But as a lab scientist, he’s mostly distant from the people behind the research and first met the family when they were invited by the school to visit in December.

After meeting the mice, they stopped at another lab, where Jake examined his blue-stained stem cells under a microscope.

“It’s me! That’s cool stuff. I’ve never seen anything like this in my life,” he said, pulling back to lean towards his father, who pulled him closer. .

Dougherty used the visit to share some news, a gift of sorts he meant to the family in person.

The missing gene does not appear to shorten life. Mice live 2 to 3 years, like their siblings.

“So, a normal lifespan?” Joe Litvag asked hopefully.

“Yes,” Dougherty replied. “As far as we can tell, identical. I know it’s a great relief too.

Joe Litvag turned to his son. “So Jake, maybe you will live to be 100 years old.”

“I’ll be 112! Jake answered with a smile.

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The Associated Press’s Department of Health and Science receives support from the Department of Science Education at Howard Hughes Medical Institute. The AP is solely responsible for all content.

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