Stories of Hope - Autism

Spotlight on Autism

Laureen Forman
San Diego, CA

Brandon's dad noticed it first. "He won't look at me," Jonathan Knepher told his wife, Laureen Forman, as they admired their 18-month-old son. "Why won't he look at me?"

Forman hadn't noticed it herself. Brandon looked at her. "What do you mean?" she asked, and then watched as her husband tried to draw their son's attention. "Oh my gosh!" Brandon would not look.

It was the first suggestion that their son had autism. Today, Brandon Knepher, 9, knows how to look at Dad. He is close to his family, Mom says, including his two younger sisters, Jadyn, who will be 7 in April, and Morgan, 4.

"The biggest challenge is with other people," Forman says. Outsiders expect Rain Man-like skills. They gawk. They judge. "When we're walking around and he's ahing and oohing, people stare at him," Forman says. "How does that make him feel?"

He is nonverbal. Behavior the family recognizes as communication, others see as acting out.

The whole view of autism needs to change, she says. "People need to realize this isn’t a psychological disorder. These kids aren't mentally ill. These children are physically sick."

Stem cell research will not only help find treatments for autism, it will help everyone adjust their notions of autism, she says. "I think it's going to revolutionize a lot," she says. "It will revolutionize the way we look at disease. It's going to change our perspective."

Toward a Cure: Autism

The neurons were different.

The electrical signaling was off, and the chemical signaling awry too. The number of cells capable of connecting the brain's two halves was also deficient.

And for people with autism, it was all good news because this was the first glimpse into the secret world of a brain with autism. Even better, the evidence Ricardo Dolmetsch gathered suggested that at least some of what was wrong could be made right.

"It's really promising. There are things we need to figure out, but I think this has enormous potential," says Dolmetsch, an assistant professor of neurobiology at Stanford University.

Studying autism in the laboratory has been a near impossible task. Animal models of this very human disease could not begin to replicate the problems in social interactions or the language difficulties that typify autism. Further, researchers cannot biopsy patients' effected tissue because it is locked away in the brain.

But Dolmetsch found a way to peek inside the brains of people with autism: He used their skin cells.

Dolmetsch collected skin cells from people with a form of autism caused by Timothy syndrome, and then, using a technique discovered in 2007, he turned back the developmental clock in the cells. They lost their mature characteristics, becoming like embryonic stem cells, capable of becoming different cell types in the body. Finally, he coaxed the cells to turn into neurons, and not just any neurons, but neurons of the cortex, the source of memory, language, and other higher cognitive functions.

When he compared the neurons generated from people without autism to those with the disease, he noticed three basic differences: the electrical signaling disruption, the lack of long-distance connections, and elevated levels of two of the chemicals that brain cells use to communicate. Norepinephrine, which plays a role in anxiety and stress, was four times to five times higher than normal, and dopamine, which is involved in attention and social behavior, was two times to three times higher.

But perhaps the most important finding was learning this neurochemical overproduction could be reversed with a drug called roscovitine. Tests in cell cultures demonstrated that some problems in autism may be reversible. It is too early to tell whether roscovitine will become a treatment. Its toxicity is unknown, as is its safety in children. It is in clinical trial as a cancer treatment, although its manufacturer is interested in pursuing trials in autism.

The Timothy Syndrome study is only the first step. "This ability to generate a biopsy of the brain creates the potential to diagnose people far, far better – especially in psychiatry – than we can now, and it provides the potential to test treatments" Dolmetsch says.

"In my opinion, this has the potential to be revolutionary.