This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.To identify and quantify changes among presymptomatic Huntington Disease (HD) gene carriers who had not yet developed definite chlorea, we performed the largest, study of individuals at-risk for HD (n=657) Subtle abnormalities in oculomotor, extrapyramidal and pyramidal motor, and cognitive measures were identified.We propose to re-examine this unique sample of at-risk individuals using an expanded test battery that includes more sensitive and specific quantitive measures for each subset of variables for which significant differences between presymptomatic gene carriers and nongene carriers were initially observed. These new measures increase the power of our proposed longitudinal studies at the rate of change among presymptomatic gene carries as they approach the manifestation of clinically diagnosable HD. These novel studies are designed to:1. Further delineate the deficits observed in the subclinical and early symptomatic phase of disease2. Measure the rate of increasing abnormality among presymptomatic gene carriers3. investigate the interrelationships among the variables so as to identify measures with similar rates of deterioration which might suggest common pathways affected early in the disease process4. quantify the relationship of CAG repeat number with disease onset and progression.The results of these studies will improve the understanding of the presymptomatic and early symptomatic phase of HD allowing for earlier diagnosis and identify subclinical biomarkers that can be utilized in clinical trials to evaluate therapeutic agents designed to slow progression and delay the onset of clinical HD.
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