Researchers at the UC Davis MIND Institute will examine whether children and youth with fragile X syndrome can improve their working memory, cognition and behavior by using an online computer-based cognitive training program, through a new $1 million grant from The John Merck Fund.
To conduct the innovative study, the researchers will travel to the homes of school-aged children around the country to instruct their families on how to use the program and deliver the intervention, called Cogmed , software designed to improve working memory that is marketed by Pearson Education.
The grant was made through The John Merck Fund’s Translational Research Program in developmental disabilities, which supports innovative research in developing treatments and improving outcomes for individuals with developmental disabilities, particularly Down syndrome and fragile X syndrome.
“I am very grateful to The John Merck Fund to have the chance to learn whether this type of training can help children with fragile X,” said David Hessl, a researcher at the MIND Institute and the study’s principal investigator. “I’ve been in the fragile X field and enjoyed working with families for many years and am excited to have the opportunity to lead a study that could help improve their lives.”
Hessl said that the study, launching early this year, will be the first to evaluate whether a computer-based cognitive training program can be effective in improving the working-memory skills, and possibly behavior, of people with fragile X syndrome.
"Although many medication trials are going on now, there never have been controlled studies of enhancing cognitive functioning in people with fragile X through behavioral training,” said Hessl, who also is associate clinical professor in the Department of Psychiatry and Behavioral Sciences.
Fragile X syndrome is the most common inherited cause of intellectual impairment, formerly termed mental retardation, and is the leading known single-gene cause of autism spectrum disorder. The United States Centers for Disease Control and Prevention (CDC) estimates that about 1 in 4,000 males and 1 in 6,000 to 8,000 females have the disorder.
“There have been surprisingly few attempts to evaluate the efficacy of behavioral or educational interventions for individuals with fragile X syndrome,” said Leonard Abbeduto, director of the MIND Institute. “Moreover, the few tested have been very limited in scope. Dr. Hessl’s extension of Cogmed is exciting, because it is a comprehensive program that can be delivered at a high dose in the home and consequently at low burden for families.”
Hessl and his colleagues hope that the intervention can be effective because it targets working memory, a serious deficit for individuals with fragile X syndrome. Hessl is collaborating with fellow MIND Institute researcher Julie Schweitzer, associate professor of psychiatry and behavioral sciences and an ADHD expert.
“I am very much looking forward to working on this project,” Schweitzer said. “It is a carefully designed study and a wonderful extension of the previous work testing the effects of cognitive training in other populations with executive functioning impairments.”
The goal of the new four-year grant will be to determine whether cognitive/behavioral training can be effective and, eventually, whether it can complement new medications under development to treat patients with fragile X.
The study will involve 100 children with fragile X between 8 and 18 years who will receive baseline assessment and training in their home. The participants will be divided into two groups, one that will receive a version of Cogmed that becomes increasingly challenging and one that does not. Families in both groups will deliver the intervention five days a week for six weeks. Researchers will check in periodically with families at distant locations via a telemedicine connection to ensure that the intervention is being delivered appropriately.
The program monitors training time and how participants are progressing. In addition, at the beginning and after training, the participants’ parents and their school teachers will be asked to rate their behavior related to executive function to see if any improvements generalize to the person’s daily life and school setting. Cogmed is providing access to the program for the research at no cost.
Hessl said that many current fragile X investigations are focused around developing targeted treatments — or medications — to improve patients’ cognition and behavior.
“There is a very heavy emphasis on pharmacological treatment of patients with fragile X that has initially been developed using animal models — so most of the clinical studies going on now are on developing effective new medications that could improve synaptic connections in the brain,” Hessl said. “If this study is successful a next step would be to see whether Cogmed works even better in children who are taking these medications. It might also open the door for studying this type of training in children with other types of intellectual disabilities.”
The research adds to the growing capabilities of the Fragile X Research and Treatment Center, one of the world’s leading fragile X clinical/research facilities, offering clinical evaluation of patients throughout the lifespan and an interdisciplinary faculty conducting clinical and basic science research to develop treatments and cures for fragile X-related conditions.
“Through this program, the fund is expanding its longstanding commitment to improving the lives of people with developmental disabilities and their families,” said Olivia Farr, chair of The John Merck Fund. “The program will make approximately 10 grant awards of $1 million each.”
“What’s especially exciting about this program,” said Marsha Mailick, chair of the fund’s Scientific Advisory Board, “is that it supports research with potential game-changing impact that is within the realm of probability — not just possibility — and could be achieved within 10 years.”
The John Merck Developmental Disabilities Translational Research Program supports researchers in developing treatments and improving outcomes for individuals with developmental disabilities, particularly Down syndrome and Fragile X syndrome (and FX associated disorders). The awards are made to the most highly innovative translational research projects that have the greatest potential of investigating rational and effective treatments and interventions for the condition being addressed.