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Of Mice and Marrow

After receiving a bone marrow transplant from a normal mouse three months earlier, the mouse at right fully recovered from the pathological grooming mutation and regrew its lost hair.
Shau-Kwaun Chen
After receiving a bone marrow transplant from a normal mouse three months earlier, the mouse at right fully recovered from the pathological grooming mutation and regrew its lost hair.

By Jenny Brundin

Salt Lake City, UT –

In a surprising new study in the journal Cell, scientists at the University of Utah have shown for the first time that the key to mental illness may lie in the immune system. The study by Nobel laureate Mario Cappechi also showed unexpected results after the mice got a bone marrow transplant. The study brings a glimmer of hope for thousands of people like Christina Pearson.

Pearson calls them "pulling trances." They sometimes lasted four hours. Reading was the most dangerous time. Her hand would wander to her head, and the compulsive hair pulling would start.

"When I would pull my hair I would feel for a certain texture," said Pearson. " I would feel for a certain sensation, a certain type of hair and then when I found the one that worked, it was if I had found gold and my nervous system would just light up."

Pearson would finish the book, a pile of long blond strands at her side. The pulling terrified her. She'd try anything to stop, put a ski mask over her head, tie her hands together. But she'd relent. Person says it felt like the behavior was part of her inner core, locked into every cell of her body.

"The urge to pull my hair was as strong as the urge to breathe," she said. "It felt like if I didn't pull my hair that I was suffocating. It was as if I was in a pool of water drowning, and struggling for air. I tried drinking myself into black outs because I found if I could black out and fall asleep, I wouldn't pull my hair."

Pearson suffers from Trichotillomania. It's a neurological disorder that causes millions of people to compulsively pull out their hair. It resembles obsessive compulsive disorder, or OCD. Pearson has closely followed the experiments of Mario Capecchi, a Nobel Prize winning-geneticist at the University of Utah. The story begins with tiny mouse embryos, the size of a grain of rice. Some of those mice developed unusual behavior-- obsessively pulling out their hair.

"They keep grooming and grooming until they remove the hair and then they keep grooming until they have lacerations," said Capecchi.

Cappechi's team had earlier discovered the reason for the odd behavior--mutations in a gene known as Hoxb8. Most scientists thought they'd find the mutant gene in the brain's nerve cells that control grooming. But to Capecchi's great surprise, it was in microglia, immune cells that originate in bone marrow and migrate to the brain.

"That was a complete surprise," said Capecchi.

The job of microglia is to clean up damage in the brain.

" Microglia are essentially the immune system of the brain," he said. "And so there is a connection essentially between the immune system and behavior which is something, nobody would have guessed, that there was a direct connection. "

Studies already pointed to connections between people with depression, OCD, Alzheimer's and other diseases and -- deficiencies in the immune system. But it wasn't clear what the connection was. Cappechi's team discovered that the genetic mutation impairs the formation of blood cells in bone marrow, leading to defective microglia. But what was more stunning was when researchers transplanted 10 mutant mice with healthy bone marrow. The mice stopped their self-mutilating grooming within four months.

" Hair grows back and these are now grooming normal periods of time so they're completely cured of that disease and they don't remove their hair anymore," Capecchi said.

The discovery that blood cells may regulate psychiatric disorders was unexpected, according to several scientists working on anxiety disorders in other mouse models. Psychiatrist Francis Lee runs a molecular neurobiology lab at Weill Cornell Medical College in New York City.

"There are these types of studies that are extremely interesting because they are not expected," he said. "They open up lines of investigation and I would say that this sort of fits into that category because, the immediate question is, how are these blood cells affecting brain circuitry and can this be and is this actually related to syndromes found in humans that respond to certain drugs."

Researchers say bone marrow transplants are too risky to cure OCD in humans. But they hope that the evidence that bone marrow can correct a psychiatric disorder in mice will inspire researchers to think about immune-based therapies. University of Utah clinical psychiatrist Dr. Dan Christensen recalls running on a treadmill at the gym with Mario Cappechi when he first heard about the discovery. "I actually had to step off and take a breath and think about this, it was kind of a shock actually," Christensen said.

Christensen says the discovery brings hope to a field that now only offers a modest control of symptoms for those with mental illness.

"That's part of what's opened up here," he said. "This different way of thinking about the diagnosis and treatment of psychiatric illness and whether in some distant day we may actually be able to reverse such disorders in humans."

Christina Pearson, founder of the Trichotillomania Learning Center, says she's deeply pleased that research is moving forward on the devastating disease of hair-pulling.

"It is amazing the stories that I've heard," she said. "One father said to me he was beating his daughter with a belt and she was lying there on the floor, saying, "Daddy, it won't help, it won't help." I've talked to the mothers of young women who have killed themselves, okay, put guns in their mouths because they could get no help."

It's been several years since Pearson has pulled her hair out. She uses medicine, therapy and group support to fight the urge. Millions of other sufferers though, haven't found the same success. This latest discovery gives Pearson hope that a medical cure can one day help them. Jenny Brundin, KUER News.

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