PREDICT-HD is an international 30-site observational study of persons at-risk for Huntington's disease (HD). PREDICT-HD capitalizes on two unique aspects of HD among neurodegenerative disorders the ability to know in advance who will develop the disease and the knowledge that all affected individuals have the same etiology (a CAG expansion in the huntingtin gene). PREDICT-HD has become part of a world-wide effort and offers an unprecedented opportunity to examine the pathophysiology and neurobiology of early HD. We seek renewal of this project to maximize the impact of this resource and test new and refined hypotheses to advance clinical trials in HD. The ultimate goal of PREDICT-HD is to define the neurobiology of HD sufficiently to allow clinical trials of potential disease-modifying therapies before at-risk individuals have diagnosable symptoms of the disease. By identifying disease state markers that are useful during this early period, PREDICT-HD will make it possible to test putative neuroprotective therapies that could delay or prevent the manifestations of disease. PREDICT-HD has successfully recruited over 1000 healthy participants who had previously undergone genetic testing for the HD expansion. Annual measures of plasma, brain imaging, cognitive performance, psychiatric symptoms, and functional capacity are obtained in concert with other demographic, clinical and genetic information. We have already identified markers of disease that are present 15 years prior to traditional motor diagnosis. The requested 5-year longitudinal continuation of PREDICT-HD will result in six products: (1) Characterization of the early longitudinal course of functional, cognitive, motor, and psychiatric change in the period encompassing 10-20 years before to 0-3 years after the traditional point of clinical diagnosis. (2) Identification of candidate biological and neuroimaging markers that have potential as useful biomarkers and possibly as surrogate endpoints in clinical trials. Developed appropriately, markers identified in PREDICT-HD could be used to reduce dramatically the number of subjects needed in future clinical trials, and/or to stratify subjects for selection in studies. (3) Refinement and standardization of the measurement of neurological and functional impairment in the earliest stages of HD development, including the point of traditional clinical diagnosis. (4) Provision of a cohort from which sub samples may volunteer for early (phase I and II) trials of candidate therapies as well as phase III efficacy trials. (5) Examination of available compounds for safety and tolerability and of their impact on newly developed disease state markers in this presymptomatic cohort. (6) Innovations in infrastructure and worldwide collaboration to serve as a model and catalyst for clinical trials in other neurodegenerative diseases.

Public Health Relevance

The PREDICT-HD study is an international 30-site observational study of 1000 persons at-risk for Huntington's disease (HD). Early markers of HD have been identified 10-20 years before the HD diagnosis is given. Continuation of PREDICT-HD will refine the markers as tools for clinical trials so that new drugs can be tested to slow and eventually to prevent HD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS040068-12
Application #
8338456
Study Section
Special Emphasis Panel (ZNS1-SRB-G (27))
Program Officer
Sutherland, Margaret L
Project Start
2000-04-01
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
12
Fiscal Year
2012
Total Cost
$5,717,035
Indirect Cost
$978,174
Name
University of Iowa
Department
Psychiatry
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Williams, Janet K; Kim, Ji-In; Downing, Nancy et al. (2015) Everyday cognition in prodromal Huntington disease. Neuropsychology 29:255-67
Matsui, Joy T; Vaidya, Jatin G; Johnson, Hans J et al. (2014) Diffusion weighted imaging of prefrontal cortex in prodromal Huntington's disease. Hum Brain Mapp 35:1562-73
Muralidharan, Prasanna; Fishbaugh, James; Johnson, Hans J et al. (2014) Diffeomorphic shape trajectories for improved longitudinal segmentation and statistics. Med Image Comput Comput Assist Interv 17:49-56
Rao, Julia A; Harrington, Deborah L; Durgerian, Sally et al. (2014) Disruption of response inhibition circuits in prodromal Huntington disease. Cortex 58:72-85
Koenig, Katherine A; Lowe, Mark J; Harrington, Deborah L et al. (2014) Functional connectivity of primary motor cortex is dependent on genetic burden in prodromal Huntington disease. Brain Connect 4:535-46
Rao, Ashwini K; Marder, Karen S; Uddin, Jasim et al. (2014) Variability in interval production is due to timing-dependent deficits in Huntington's disease. Mov Disord 29:1516-22
Harrington, Deborah L; Liu, Dawei; Smith, Megan M et al. (2014) Neuroanatomical correlates of cognitive functioning in prodromal Huntington disease. Brain Behav 4:29-40
Kim, Eun Young; Magnotta, Vincent A; Liu, Dawei et al. (2014) Stable Atlas-based Mapped Prior (STAMP) machine-learning segmentation for multicenter large-scale MRI data. Magn Reson Imaging 32:832-44
Downing, Nancy R; Kim, Ji-In; Williams, Janet K et al. (2014) WHODAS 2.0 in prodromal Huntington disease: measures of functioning in neuropsychiatric disease. Eur J Hum Genet 22:958-63
Georgiou-Karistianis, Nellie; Long, Jeffrey D; Lourens, Spencer G et al. (2014) Movement sequencing in Huntington disease. World J Biol Psychiatry 15:459-71

Showing the most recent 10 out of 80 publications