Groundbreaking New Down Syndrome-Specific Cognitive Test Battery Developed to Enable New Clinical Trials and Advanced Research
Groundbreaking new research describing the development and validation of the new Arizona Cognitive Test Battery (ACTB) for individuals with Down syndrome has just been published in the September, 2010 issue of the Journal of Neurodevelopmental Disorders. Down Syndrome Research and Treatment Foundation (DSRTF) Innovation Research Grant recipients Drs. Jamie Edgin and Lynn Nadel at the University of Arizona, together with their research collaborators, describe the state-of-the-art ACTB as the first cognitive test battery specifically designed for use in individuals with Down syndrome across a range of ages and ability levels. This novel and highly specific cognitive test battery significantly enables assessment of therapeutic efficacy in new drug clinical trials and identification of factors influencing cognitive disability and variability.
Previously, most neuropsychological assessments of cognition have utilized global cognitive tests, e.g., IQ tests, not specifically designed or properly validated for use in individuals with developmental and intellectual disabilities such as Down syndrome. Such previous tests lack the ability to specifically focus on, evaluate and measure functions of specific brain regions and cognition affected in Down syndrome. Assessments with previous tests can be significantly limited due to variability in language and attention abilities among individuals as well as insensitivity in measuring changes in outcome studies, such as clinical trials and educational or intervention studies.
Importantly, the new ACTB addresses and overcomes such problems with these previous global cognitive tests because the integrated components of the ACTB have been specifically designed and validated to:
- Assess cognitive function in prefrontal cortex, hippocampus and cerebellum - all brain regions demonstrated to be involved in cognitive dysfunction in Down syndrome;
- Integrate a set of non-verbal-based tests so as to separate neuropsychological skills from language demands, and include properties to enhance adaptability across cultures, age ranges and different testing contexts;
- Allow for correlation of variability of cognitive functions with specific genetic variability and advanced genetic association studies which may also lead to identification of new therapeutic targets and clinical outcomes;
- Link function in specific brain regions across species serving as a critical bridge to accelerate translation of drug studies in animal models to human clinical trials; and,
- Provide highly sensitive measures of cognitive function specific to Down syndrome enabling determination of therapeutic efficacy, i.e. clinical outcomes, in new drug clinical trials.
As has been widely reported, a significant number of drug development candidates fail at later clinical trial stages because efficacy, i.e., relevant clinical endpoints, cannot be successfully measured or proved. This has been particularly true in clinical trials for drug candidates being developed for improvement of cognition related to various disorders, specifically including new potential drugs for Alzheimer’s disease. “As we continue to accelerate toward clinical trials for new drug candidates to improve cognition in children and adults with Down syndrome, it is essential to have highly specific and sensitive tests such as the new ACTB that can successfully determine efficacy in cognitive improvement,” says Dr. Michael Harpold, DSRTF Chief Scientific Officer and Chair, Scientific Advisory Board.
The development of the ACTB adds an important new tool for advancing cognition research for Down syndrome, and has already generated wide international interest among researchers and clinicians, including the biopharmaceutical industry. Drs. Edgin and Nadel are also now using the ACTB in the first detailed investigation of the correlation of sleep problems in Down syndrome with cognitive functions. In addition, these researchers are using the ACTB in collaboration with Dr. Roger Reeves and a consortium of researchers at five other biomedical research institutions as a critical part of the Down Syndrome Cognition Project (DSCP) to investigate specific correlations between genetic and cognitive variability among individuals with Down syndrome and establish a scaffold for a new clinical trials network. Both of these ongoing projects are supported by DSRTF Research Grants.
“A key part of the comprehensive new research strategy that we have developed and implemented involves targeted research funding to address rate-limiting steps and emergent ‘roadblocks’ throughout the drug discovery and development process pipeline, from discovery through translational research including clinical trials to approval of effective and safe new therapies,” adds Dr. Harpold. “The completion of the development and initial validation of the new ACTB by Drs. Edgin, Nadel and their collaborators represents the latest critically important example to further accelerate progress. DSRTF joins with Drs. Edgin and Nadel in gratefully thanking the individuals with Down syndrome and their families for participating in and contributing to this new study and each of DSRTF’s generous donors and supporters, all of whom made the development of the new ACTB and the essential DSRTF research grant support for this study possible.”
Since its founding in 2004, DSRTF has generated more than $7 million, including more than $440,000 in direct grant support to Drs. Edgin and Nadel at the University of Arizona, to fund and support major new results-driven biomedical research to improve cognition for individuals with Down syndrome.
To read a full copy of the new research article, Development and Validation of the Arizona Cognitive Test Battery for Down syndrome (2010) J. O. Edgin, G. M. Mason, M. J. Allman, G. T. Capone, I. DeLeon, C. Maslen, R. H. Reeves, S. L. Sherman & L. Nadel, Journal of Neurodevelopmental Disorders 2: 149-164, click here.
For additional earlier information concerning the development of the ACTB at the University of Arizona, click here.
For additional information about participating in ongoing and future cognitive studies conducted by Drs. Edgin and Nadel and the Down Syndrome Research Group (DSRG) at the University of Arizona, click here.