DISEASE-A-WEEK CHALLENGE #5: The California Stem Cell Program vs. Autism
by Don C. Reed
Before I met the boy who liked Stanford too much, I knew almost nothing about autism.
I had seen the movie, RAINMAN, in which Dustin Hoffman played an autistic person. He seemed like a genius with emotional problems: he could instantly count spilled toothpicks, memorize phone books, play cards at Las Vegas– but was terrified of physical contact, shrieking if hugged.
But there at the door of my 8th grade classroom was a boy in a bright red sweater, telling me Stanford was the greatest university in the world.
He wore that red sweater every day, hot or cold. And every essay he wrote—almost every sentence that he wrote—was about Stanford.
If the assignment was an in-class essay on sharks, he would frown and freeze, sitting motionless for two or three minutes. Then he would smile, and I knew he had found a way to work the subject around to Stanford, which did not have any aquarium for sharks, but if it did, that shark aquarium would be the best in the world, because…
His writing was neat, his thinking well-organized, as long as you wanted to talk about Stanford. If the subject was anything else, he would tune out.
On the writing he produced, he earned an A. In my class, he was successful.
Some high-achieving autistic adults can be valuable and effective employees, if a company’s needs coincide with their own. They can remain focused on one subject for astonishingly long periods of time.
Others are not so fortunate.
In an open letter to the California stem cell program, Nicki P. spoke about her 9-year-old child, Christopher.
“At two, Christopher was normal, a cheerful intelligent boy…
“But on March 21, 1999, he said, ‘I’m finished, all finished,’ repeating the phrase for days…
“At age 9, he cannot read, write, or even hold a pencil appropriately. His limited speech is unclear, sometimes even to me. He cannot access many of the skills he had as a toddler, and needs help with almost all daily living skills…(My fear is that) he will end up in a home that will not understand his two-to-three-word-requests, and he will not have me to advocate for him…”
Eight years later, I made contact with Ms. P. again. Her son Christopher, now 17, was functioning at the level of a two-year-old.
“Sometimes, when I am asleep,” she said, “he wakes up, comes quietly into my bedroom, and dives through the air to crash-land on top of me—like he used to do, when he was two.”
Ms. P. was quoted in a newspaper article about the tragic murder/suicide of another mother of an autistic child– for whom the strain became too much.
A woman called Elizabeth H. shot and killed her 22-year-old autistic son, and then herself. She had been trying to get help for him, but state budget cuts took away her hope. Apparently, when her son was of school age, assistance was available; but once he turned 21, his eligibility ended.
No one can condone murder/suicide. But Ms. P. points to a problem which must be faced.
“Our system has crumbled,” she said, “The disabled, elderly and chronically ill are being left behind…
“…the problem will only grow worse, as autistic children nationwide become adults…(and) states cut more social and medical services…”
In monetary terms, how big a problem is autism?
“It can cost about $3.2 million to take care of (one) autistic person over his or her lifetime. Caring for all people (U.S. citizens)…costs an estimated $35 billion per year.” (emphasis added)
But the California stem cell program is fighting for cure.
Meet Dr. Alysson R. Muotri, of UC San Diego, funded by the California Institute for Regenerative Medicine (CIRM, the Proposition 71 initiative approved by California voters ).
A slender, energetic man, originally from Brazil, Dr. Muotri had been trying to gather tissue samples from autistic children.
“Taking blood samples from autistic children is… not nice,” he said when I interviewed him, “They scream and fight…. So, we came up with the Tooth Fairy program.”
When an autistic child lost a baby tooth, they could donate it to Dr. Muotri’s program.
“It was so successful we got more teeth than we needed!”, he said.
Dr. Muotri had three main goals for his research. First, there had to be a microscopic human model of the disease, so he could test drugs on it, see which therapies helped and which did not. Second, he wanted to find a “molecular footprint” for the disease, like finding the tracks of a predator. That way newborns could be tested; the earlier they were diagnosed with the disease, the better the chance for a positive outcome.
Third and most importantly, he hoped to actually reverse the disease.
The California stem cell program offered a chance. As his weapon of choice, Muotri picked Induced Pluripotent Stem cells, similar to embryonic stem cells, but made from patient body tissues. Why not human embryonic stem cells, (hESCs)? Dr. Muotri said he wanted stem cells directly from an autistic person, and so they had taken tissue samples—from inside the donated baby teeth.
Muotri changed the tissue samples into embryonic-like cells. Then (in a process taking about three months) he converted those cells into brain cells, like those of the patient.
Now he had diseased brain cells to work with in the lab: almost like a living autistic brain.
He found that neurons (nerve cells) derived from autistic patients make less connections than do those from healthy individuals. Diseased astrocytes—a star-shaped cell type in the brain—contributed to these connection shortfalls. But if healthy astrocytes were added, they could help recovery.
He found some experimental drugs that the malfunctioning neurons seemed to like, and which seemed to reverse the effects of autism. The experiment is new as this article is written, but there is reason to hope. Most of his work has been done with human cells in a “disease in a dish” model. Naturally Dr. Muotri wants to go ahead, possibly trying for one of CIRM’s Disease Team grants, which would provide enough funding to go all the way into human trials.
How does he feel about this?
“The possibility of helping people with autism is so exciting. (We are eager) to see the results of candidate drugs we’re screening against autism…
“We should complete the screening of 55,000 drugs on astrocytes derived from (the tissue samples from teeth)… Around 5,000 are re-purposed drugs (which have already gone through much FDA testing) so if we get a hit on these, clinical trials are around the corner.
“When I talk to parents now, I see hope in their eyes, that there is a light at the end of the tunnel.
“And when I get up in the morning every day, I run to my lab…”
Update: In stark contrast to the California effort, Illinois’s Republican Governor Bruce Rauner recently eliminated state funding for autism programs—and he did it on April 2, World Autism Awareness Day.
Don C. Reed is the author of the forthcoming book, STEM CELL BATTLES: Proposition 71 and Beyond.