The Prospective Huntington At Risk Observational Study (PHAROS) was initiated by the Huntington Study Group (HSG) in 1999 to characterize and measure the clinical onset of Huntington?s disease (HD) in a diverse cohort of individuals who are at immediate risk (50:50) for having inherited the HD gene. Participants include healthy adults, age 30-55 years, who have not undergone testing for the HD gene and who wish to remain unaware of their HD gene status, yet are interested in contributing to knowledge about HD through research. Under a stringent arrangement that conceals genetic information, a blood sample is obtained from participants to measure the cytosine-adenine-guanine trinucleotide repeat (GAG) of the HD gene. Standardized clinical assessments are carried out at about 9-month intervals for up to 7 years of prospective observation by investigators who are also kept unaware of HD gene status in order to define early, HD-gene specific signs predictive of manifest disease. Nearly 500 research participants have already been enrolled in PHAROS at 36 sites in the U.S. and 6 in Canada. We plan to enroll the entire cohort of 1000 participants by November 2001, and request prospective follow up of all PHAROS participants to a planned conclusion in 2006. PHAROS will provide objective knowledge about the positive predictive value and reliability of early clinical signs of HD and their relationship to CAG and other genetic and environmental modifiers. Only 3 percent of adults in the U.S. who are at immediate risk to develop HD have chosen to undergo presymptomatic predictive testing for the HD gene, but relatively little is known about the 97 percent who have not. PHAROS will lead to an understanding of the feasibility, psychosocial, ethical, confidentiality and legal issues relevant to this under-studied majority of at-risk individuals who have chosen not to learn of their HD fate. Collectively, completion of PHAROS will: 1) refine the relationship between clinical predictors of HD onset and CAG, 2) help identify other genetic and environmental modifiers of HD onset, 3) enhance the feasibility, safety, efficiency, ethical conduct and success of preventive trials aimed at delaying HD onset, and 4) provide new insights for and improve care of individuals who risk developing this fatal neurogenetic disorder.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
5R01HG002449-02
Application #
6666693
Study Section
Ethical, Legal, Social Implications Review Committee (GNOM)
Program Officer
Thomson, Elizabeth
Project Start
2002-09-30
Project End
2007-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
2
Fiscal Year
2003
Total Cost
$1,115,203
Indirect Cost
Name
University of Rochester
Department
Neurology
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
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Chao, Michael J; Gillis, Tammy; Atwal, Ranjit S et al. (2017) Haplotype-based stratification of Huntington's disease. Eur J Hum Genet 25:1202-1209
Quaid, K A; Eberly, S W; Kayson-Rubin, E et al. (2017) Factors related to genetic testing in adults at risk for Huntington disease: the prospective Huntington at-risk observational study (PHAROS). Clin Genet 91:824-831
Huntington Study Group PHAROS Investigators; Biglan, Kevin Michael; Shoulson, Ira et al. (2016) Clinical-Genetic Associations in the Prospective Huntington at Risk Observational Study (PHAROS): Implications for Clinical Trials. JAMA Neurol 73:102-10
Genetic Modifiers of Huntington’s Disease (GeM-HD) Consortium (2015) Identification of Genetic Factors that Modify Clinical Onset of Huntington's Disease. Cell 162:516-26
Sharp, Madeleine E; Caccappolo, Elise; Mejia-Santana, Helen et al. (2015) The relationship between obsessive-compulsive symptoms and PARKIN genotype: The CORE-PD study. Mov Disord 30:278-83
Marder, Karen; Gu, Yian; Eberly, Shirley et al. (2013) Relationship of Mediterranean diet and caloric intake to phenoconversion in Huntington disease. JAMA Neurol 70:1382-8
Killoran, Annie; Biglan, Kevin M; Jankovic, Joseph et al. (2013) Characterization of the Huntington intermediate CAG repeat expansion phenotype in PHAROS. Neurology 80:2022-7
Moscovitch-Lopatin, Miriam; Goodman, Rachel E; Eberly, Shirley et al. (2013) HTRF analysis of soluble huntingtin in PHAROS PBMCs. Neurology 81:1134-40
Biglan, Kevin M (2010) Tapping in Huntington disease: a path forward to preventive therapies? Neurology 75:2142-3

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