Neurobehavioral Phenotypes in MPS III
Hypothesis #1: Factor analysis of the revised Sanfilippo Behavior Rating Scale (SBRS) will identify a group of externalizing behaviors and a group of Klüver-Bucy syndrome-like behaviors as two different factors that are at least partially independent.
Hypothesis #2a: Children with MPS III will show more hyperlocomotion, fearlessness, asociality and noncompliance than children of similar cognitive ability with MPS I.
Hypothesis #2b: These behaviors will become more frequent and/or intensify over time, consistent with the Cleary and Wraith (1993) model. Quantifying them will provide a more empirical framework for staging disease progression.
Hypothesis #3: Brain volumetric analysis and diffusion-tensor imaging will reveal abnormalities of frontal and temporal lobe structures that will correlate with externalizing and Klüver-Bucy syndrome-like behaviors, respectively.
Hypothesis #4. Loss of cognitive and language function as measures of neurologic decline will directly precede or co-vary with behavioral decline.
The primary objective of this study is to identify the behavioral phenotype and its neural basis in MPS III (Sanfilippo syndrome). Is the behavioral phenotype similar to that of Klüver-Bucy syndrome, and is there evidence for amygdala abnormality? The secondary objective of this research study is to develop easily administered, sensitive and specific neurobehavioral and neuroimaging markers to characterize the behavioral phenotype(s) of MPS III; to track their progression; and to delineate their neural substrates. Such markers are critical for identifying the stage of disease for each patient, and to measure treatment outcome. Although we know that severe cognitive decline is one essential characteristic of MPS III, the other highly salient characteristic is a range of abnormal and disruptive behaviors that can include, but go well beyond, childhood noncompliance and oppositionality. These behaviors set Sanfilippo syndrome apart from the other MPS disorders. They cause major disruption in the child's familial, school, and community environments. Delineating these behavioral abnormalities will help in better understanding the neurological disease.
Sanfilippo Syndrome Type A
Sanfilippo Syndrome Type B
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Characterizing the Neurobehavioral Phenotype(s) in MPS III|
- Assessment of Temperament [ Time Frame: Within One Year of Enrollment ] [ Designated as safety issue: No ]Using Risk Room procedures of the established "Laboratory Temperament Assessment Battery" (Lab-TAB), the investigators will measure and record each subject's startle, exploration (fear), compliance, and attachment.
- Quality of Life Measures [ Time Frame: Within One Year of Enrollment ] [ Designated as safety issue: No ]Assessments of research subjects' quality of life will be made using age-appropriate standardized assessment tools.
- Event-Related Potentials Measurement [ Time Frame: Within One Year of Enrollment ] [ Designated as safety issue: No ]High-density Event-Related Potentials (ERPs) will be elicited and recorded. ERPs provide information about the timing and location of neurocognitive processes associated with the individual's processing of discrete stimuli. Two sets of stimuli will be used: 1. auditory stimuli consisting of non-language sounds and phonemes; and 2. visual stimuli consisting of images of emotional faces. All stimuli will be presented in an oddball paradigm format (repetition of stimuli with a random insertion of a novel stimulus).
- Magnetic Resonance Imaging Examination [ Time Frame: Within One Year of Enrollment ] [ Designated as safety issue: No ]To examine the neural substrate of MPS III behavioral phenotypes of participating research subjects, the investigators will perform high-resolution brain volumetric magnetic resonance imaging (MRI) during clinical scans.
- Assessment of Cognitive Development [ Time Frame: Within One Year of Enrollment ] [ Designated as safety issue: No ]Research subjects' cognitive development will be assessed using age-appropriate standardized assessment tools.
|Study Start Date:||December 2010|
|Study Completion Date:||August 2014|
|Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
Like some other mucopolysaccharidosis (MPS) syndromes, MPS III (Sanfilippo syndrome) is characterized by a severe cognitive decline ending in dementia and death. Unlike other MPS syndromes, earlier-stage MPS III is also associated with a range of abnormal and disruptive behaviors that can include, but go well beyond, childhood noncompliance and oppositionality. These behaviors, which cause major disruption in the child's familial, school, and community environments, set MPS III apart from the other MPS disorders. These behaviors may also indicate the identity of the neural pathways affected in this disease; their sequence of onsets may indicate the order in which these pathways are affected. We propose to define and categorize the behavioral profile(s) or phenotype(s) of MPS III and correlate them with clinical quantitative neuroimaging in order to understand the neural bases of the disease. In addition, we will use these results to develop a set of sensitive and specific measures that can be easily administered by health care professionals to help monitor the disease and the efficacy of future treatments.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01873911
|United States, Minnesota|
|University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Elsa G Shapiro, PhD||University of Minnesota - Clinical and Translational Science Institute|
|Principal Investigator:||Michael Potegal, PhD||University of Minnesota - Clinical and Translational Science Institute|