A Full-Service Clinical Research Organization

Apr 17 2019

Illuminating Results from a Natural History Study

Christopher Gallant, Senior Manager, Client Relations, PROMETRIKA, LLC.

Recently, our own Nicole LaVallee, PhD (Director of Biostatistics) and Miganush Stepanians, PhD (President & CEO and senior advisor in Biostatistics) collaborated with the scientists at Boston Children’s Hospital on analyses of the Angelman Syndrome Natural History Study. The results of this collaborative effort were published in the American Journal of Medical Genetics1.  We are proud of our work with the amazing group of scientists dedicated to helping children and adults living with this debilitating, rare genetic disorder.

Angelman Syndrome (AS) is a rare neurogenetic disorder that results in severe intellectual disability, and severe impairment of speech and language, and fine and gross motor skills. A majority of individuals with AS exhibit self-injurious behaviors, stereotypies (e.g., hand flapping), and anxiety symptoms. These maladaptive behaviors often result in increased parental stress and reduced quality of life for both the individual with AS and his or her family. The expectation is that if the maladaptive behaviors are better controlled, self-help skills and attention span can improve. This, in turn, will result in decreased parental stress and improved quality of life for the individual with AS and his or her family.

Assessments of maladaptive behaviors are important endpoints for clinical trials examining the use of novel therapies for individuals with AS.  The study of these problem behaviors prevalent in AS will help guide the development of pharmacological treatments targeting these specific behaviors. One of the goals of the analyses conducted by our team was to help establish baseline behavioral norms for maladaptive behaviors in the AS population using standardized, validated instruments against which future clinical trial assessments may be evaluated.

The AS Natural History Study focused on whether maladaptive behaviors within the AS population vary in severity based on genotype, developmental level, chronological age, or sex.  Caregivers of 301 individuals with AS were asked questions about the participant’s behavior and completed the Aberrant Behavior Checklist-Community version (ABC-C). Developmental functioning was evaluated with either the Bayley Scales of Infant Development, Third Edition (Bayley-III) or the Mullen Scales of Early Learning (MSEL). Family functioning was assessed using the parent-completed Parenting Stress Index (PSI) and the Family Quality of Life questionnaire (FQoL).

Results of the analyses confirmed that maladaptive behaviors, particularly hyperactivity, irritability, and aggression, adversely affected parental stress and family quality of life. Of particular interest was the result that higher cognitive functioning was associated with increased irritability. Hyperactivity and irritability increased with age across all genotypes and should be ongoing targets for both behavioral and pharmacological treatment.

Armed with these insights, researchers may be able to find treatments that correct or modify abnormal gene expression and address behaviors that affect quality of life. PROMETRIKA plans to be part of this ongoing search.

1 Sadhwani A, Willen JM, LaVallee N, Stepanians M, Miller H, Peters SU, et al. Maladaptive behaviors in individuals with Angelman syndrome. Am J Med Genet A 2019 Jun;179(6):983-992.

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