Rett syndrome, a neurodevelopmental disorder affecting mostly girls, takes away the ability to speak, and this makes the condition hard to reliably measure and assess. But children with Rett syndrome also display distinctive hand movements or stereotypies, including hand wringing, clasping and other repetitive hand movements, visible in many of these videos. With help from a grant from Boston Children’s Hospital’s Innovation Acceleration Program, researchers are transforming these hand movements into an assessment tool.
Until now, there has been no quantitative measure for monitoring Rett hand movements. Adapting commercially available wearable sensor technology, biomedical engineering researcher Heather O’Leary has created a bracelet-like device not unlike Fitbit, another wearable accelerometer used to monitor exercise activity levels.
“We are hoping this technology can act as an objective biomarker that would allow clinicians to effectively and efficiently analyze hand stereotypies over time,” says O’Leary, who is collaborating with Walter Kaufmann, MD, director of the hospital’s Rett Syndrome Program.
Clinical studies spur biomarker quest
Rett syndrome currently lacks any meaningful treatment, but recent research in mice with the equivalent of Rett syndrome has made researchers and caregivers hopeful that new treatments may reverse Rett symptoms. In 2011, Boston Children’s initiated a human study of human insulin-like growth factor (IGF-1), the first clinical drug trial seeking to alter Rett syndrome’s underlying cause.
The results, published in January 2014, show that IGF-1 is safe and well tolerated in girls with Rett syndrome, and helps certain breathing and behavioral problems associated with the disorder.
But the research team needed tangible measures of improvement. “It was clear from the beginning that we didn’t have a great way to analyze the hand stereotypies, which are unrelenting during wakeful periods,” O’Leary explains.
Traditionally, such evaluations involve caregiver reports, clinical observation and video monitoring, all of which can be subjective and time-consuming. “If we can objectively quantify these hand movements, then maybe we can start evaluating bigger questions—like identifying the factors that influence each stereotypy and its impact on the individual,” says O’Leary.
In addition, the team hopes the biomarker tool will help them understand stereotypies’ impact on purposeful hand use, assess their association with treatable symptoms such as anxiety and emotional disturbances and measure treatment efficacy.
Sensor technology creates individualized patterns
A Phase 2 clinical trial of IGF-1 for Rett syndrome opened at Boston Children’s in March 2013, along with a biomarker study using the Q-sensor Curve bracelet—originally built and sold by Affectiva, Inc.—to track hand movements. During a 20-week placebo-treatment phase and a 20-week IGF-1 segment, each child wears the bracelet on both wrists, while the embedded accelerometer tracks and records her hand movements. Recordings are made several times throughout each treatment segment, including six 24-hour recordings at home dispersed over the 40-week trial. (The trial is now fully enrolled.)
The bracelet collects many types of data. “We are looking at the frequency of the activity of each hand, its duration and the amplitude or amount of activity,” O’Leary explains.
When all the data are plotted on a 3-dimensional space, patterns are clearly visible that could help clinicians monitor their patients. “It will be particularly useful if we can collect data outside of the laboratory environment to give us a better sense of what is happening in a patient’s life in the real world,” adds O’Leary.
And once objective measures have been established in these girls with Rett syndrome, the team hopes to use the Q-sensor to study hand stereotypies in other neurodevelopmental disorders such as autism spectrum disorder.
Alice McCarthy is a science writer covering biomedical research and the latest in new medical treatments.