G l i m m e r s o f h o p e i n a u t i s m r e s e a r c h
A CLINICAL STUDY participant who asks his attending nurse for a date might ordinarily raise some eyebrows and set off some alarms. But when that happened during a study that UC Davis developmental and behavioral pediatrician Randi Hagerman was conducting, she was overjoyed. The study participant in that case was a severely autistic adult male in his 20s who had fragile X syndrome, the focus of much of Hagerman’s research for the past three decades. Fenobam, a metabotropic glutamate receptor 5 (mGluR5) antagonist she was investigating, had induced a startling improvement in the behavior of the usually withdrawn man.
“The man was really agitated, hyperactive and showed poor eye contact as the nurse from the CTSC set up his IV to do repetitive sampling,” said Hagerman, the medical director of the UC Davis MIND Institute, professor of pediatrics and holder of the Endowed Chair in Fragile X Research. “After he was given fenobam, he suddenly calmed down, was able to have good eye contact – and later in the day asked the nurse for a date. I couldn’t believe it. That was one of the most exciting days we have ever had, and it gave me a lot of hope. I thought, ‘Oh, my God. I think we’ll be able to cure this problem.’”
Hagerman and numerous colleagues are investigating a protein called FMRP, the levels of which are suppressed in people with fragile X syndrome, as well as in some people with autism. “The CTSC has helped us with a number of trials, funded by the National Fragile X Foundation and pharmaceutical companies that are developing new medications to treat fragile X syndrome. We have about nine controlled trials of these medications under way. The CTSC has been very helpful to us in the grant application process and in carrying out the studies,” Hagerman said. “Our goal is to reverse intellectual disabilities and autism in individuals with fragile X, and also individuals with idiopathic autism. A CTSC nurse has helped us carry out some of those studies, which we couldn’t have done otherwise. The CTSC facilitates translational research, and it is critically important for all of our studies.”
Hagerman is encouraged by the number of researchers engaged in a wide variety of autism and fragile X syndrome investigations at the MIND Institute and with the involvement of the CTSC.
“Flora Tassone at the MIND Institute developed a blood spot test, enabling newborn screening for fragile X during the past four years under an NIH grant,” Hagerman said. “David Hessl on our team is conducting a study using computing to enhance attention and concentration problems in individuals with fragile X syndrome. We’re looking at iPad applications in a study by Maria Diez for children with autism or fragile X syndrome, and we’re conducting a literacy study. Kerrie Lemons-Chitwood is looking at reading interventions for individuals with fragile X syndrome,” she continued, running out of fingers as she counted the many projects under way. “Len Abbeduto, the new director of the MIND Institute, has conducted a language-intervention study, exploring how individuals with fragile X syndrome learn language in comparison to individuals with idiopathic autism. He also has a new study looking at transitions into adulthood.”
UC Davis researchers investigating autism also include Irva Hertz-Picciotto, a professor in the Department of Public Health Sciences and chief of its Division of Environmental and Occupational Health. Hertz-Picciotto (pronounced pih-CHOH-toe) investigates environmental factors such as air pollution, pesticides and nutrition, which may increase or decrease the risk that a child develops autism or other neurodevelopmental delays. She oversees or participates in three large ongoing studies in which the CTSC plays a significant role.
“We’ve worked with the CTSC on the CHARGE study, but it has been extremely helpful to us with the MARBLES study,” said Hertz-Picciotto, deputy director of the UC Davis Center for Children’s Environmental Health and director of the Program in Environmental Epidemiology of Autism at the MIND Institute. “Participants in the MARBLES study are women who have a child with autism and are pregnant with another child. We needed to collect information about the home environment as well as numerous blood samples during the pregnancy and then later from the child. To make this protocol as convenient as possible for families, we wanted to schedule home visits rather than requiring them to come into the clinic. Because we needed assistance, I contacted the CTSC at the very beginning.”
The CTSC assigned staff phlebotomist Mary Tofflemire to travel with coordinators to the homes of participants throughout Northern California (as the accompanying article describes). “Because they already have another child with serious developmental problems, many of these mothers who are pregnant or have recently given birth are very stressed. So the CTSC’s home visit services have been enormously beneficial, a major contribution to the study,” Hertz-Picciotto said.
She also credits the CTSC with helping her retain postdoctoral researcher Rebecca Schmidt, a participant in an autism research training program at the MIND Institute. “When she finished her postdoctoral fellowship, the Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) scholars program, administered through the CTSC, provided her with funding to launch her career,” Hertz-Picciotto said. Schmidt has been engaged in pioneering studies of relationships between folic acid and autism.
The cross-disciplinary infrastructure of the CTSC is especially important to Hertz-Picciotto. “Our studies have involved a number of people who are characterizing a great many features of immunologic disregulation in children with autism. That work has opened up another whole area of inquiry for me about how the immune system and the brain depend on each other for development,” Hertz-Picciotto said. “I might never have done that if the CTSC had not put me in touch with these other scientists.”