As reported by The Hartford Courant, October 11, 2010.
UConn Researchers Make Breakthrough in Two Puzzling Disorders
Stem Cells Used to Create New Research Tool for Two Diseases
By William Weir
University of Connecticut researchers have created genetic models of two devastating diseases, providing what could be a useful tool for studying the causes of the disorders.
The research team used stem cells to create the models of Prader-Willi Syndrome and Angelman Syndrome. The study appeared in the Sept. 27 edition of the Proceedings of the National Academy of Sciences. It was led by Stormy Chamberlain, an assistant professor of genetics and developmental biology at the UConn Health Center.
Soon after birth, children born with Prader-Willi Syndrome have difficulty feeding and develop poor muscle tone. Starting about age 2, they develop an insatiable appetite. Their chronic hunger lasts for their lifetime; the urge to eat is so severe, PWS sufferers often must live under constant supervision and in places where all food storage is locked down. Extreme obesity and retardation are common traits of among those with PWS. Experts believe that Prader-Willi Syndrome affects 1 in 15,000 people.
Those born with Angelman Syndrome suffer speech difficulties, seizures, problems with motor control and balance, and serious intellectual disabilities. Estimates of its prevalence range from 1 in 10,000 to 1 in 20,000.
What connects the two diseases is that they're both caused by an abnormal chromosome, in each case, the 15th of 23. In PWS, the abnormal chromosome is passed on by the father; in Angelman Syndrome, it comes from the mother.
Because the cells are in the brain, researchers haven't had access to study them.
"We can't biopsy the brain of patients for research, that's clear," said Mark Lalande, director of UConn's Stem Cell Institute and senior author of the study. Research has largely been limited to studying mice with genetically induced versions of the diseases, he said.
"It's a helpful model, but the brain of a mouse is obviously different from that of a human," Lalande said.
By taking skin cells from patients with the diseases, they were able to create a type of stem cell called induced pluripotent stem cells, and coax them into neurons.
"We were very surprised and delighted that we were able to create live neurons from these individuals," Lalande said. With live neurons in a dish, researchers will be free to experiment with them. Lalande said the genetic models allow for screening different drugs that could treat the disease symptoms — for instance, appetite control.
"The real potential application is you could set up thousands of these, and add different drugs and see which ones are correcting some of the molecular disorders," he said. "That's what we're really looking at these for, to try to understand the molecular basis of the two diseases."
The study was funded in part by the Foundation for Prader-Willi Research. Theresa Strong, who is chairwoman of the organization's scientific advisory board, said the research should go a long way toward removing many of the obstacles in researching the disease.
"We don't know much about the neurobiology of PWS, and that's where the problems lie," she said. "A lot of diseases we can recapitulate in the mouse, but that doesn't really work with PWS, because the genetics are a little different."