Doctors have completed the first step of a unique medical research study, evaluating 1,001 individuals at risk of developing Huntington's disease who do not know - nor do they want to know - whether they carry the genetic defect that causes the condition.
An international team led by neurologist Ira Shoulson, M.D., of the University of Rochester Medical Center is trying to identify the earliest signs of the onset of the disease. The information will help clinicians design better studies of new drugs aimed at alleviating or postponing illness. It also helps researchers understand how patients evaluate potentially life-changing knowledge now available to patients through means such as genetic testing.
Shoulson and colleagues from the Huntington Study Group reported their progress on the study known as PHAROS, or Prospective Huntington At Risk Observational Study, in the July issue of the Archives of Neurology.
While the gene that causes the disease is known and can be identified through a blood test, fewer than one in 10 adults at risk for developing the disease have chosen to be tested. People at risk but who have not taken the test have a 50/50 chance of developing the disease. This at-risk group offers physicians a unique opportunity to witness the earliest signs of the disease, before anyone knows whether a person actually has the gene for Huntington's or not.
In the PHAROS study, one of the largest Huntington's studies ever undertaken, 1,001 healthy people between the ages of 26 to 55 who had at least one parent with the disease have stepped forward to participate. Patients, doctors and nurses from 43 hospitals and medical centers around North America, including Rochester, are taking part.
At enrollment in PHAROS, participants provide a blood sample to analyze whether or not they harbor the Huntington's gene, though neither they, the researchers, nor their physicians will ever be told the results of the individual analyses. Participants are being evaluated once every nine months for anywhere from four to 10 years.
"The at-risk individuals who are participating in PHAROS do not know if they have inherited the gene responsible for Huntington's disease or if they will ever even develop this serious disease," said Shoulson, who chairs the Huntington Study Group. "The enthusiasm and commitment of these individuals to participate in this type of long-term research is gratifying. We expect that the knowledge from this observational study will be put to good use when we begin clinical trials to delay the onset of Huntington's disease."
Huntington's is an inherited disorder that affects about 30,000 people in North America; another 150,000 people or so may have the gene that causes the disease. The defective gene, a sort of genetic stutter, leads to the destruction of brain cells, causing involuntary movements, cognitive problems, and often psychological problems like depression and paranoia. The disease usually strikes in young- to mid-adulthood, in a patient's 30s or 40s.
The study is relevant for many physicians and patients who have increasing access to information about the specific genetic causes of many diseases, even for conditions like Huntington's for which there is no cure or approved treatment. The issues these patients face portend concerns that nearly everyone will confront eventually, as researchers ferret out the genes that predispose some people to heart trouble, high blood pressure, Alzheimer's and Parkinson's diseases, stroke, and other diseases. People at risk for Huntington's disease today present a unique opportunity for researchers to examine the psychosocial, ethical, and practical issues faced by people who have chosen not to know whether they will develop a serious disease or not.
"The experience from PHAROS also informs us how persons at high risk to develop a disabling genetic disease deal with lingering uncertainties about their future health and complex choices about their participation in research," said Shoulson, part of a Rochester team that treats Huntington's patients from more than 200 families.
The group that has signed up is remarkably healthy, with more than 99 out of 100 participants either showing no detectable signs of Huntington's or a symptom not necessarily tied to the disease. Nearly all participants are employed, with the majority in professional or managerial jobs; overall the group of participants is highly educated, with nearly half having at least four years of education after high school. For reasons that researchers don't understand, more than twice as many women as men, 689 compared to 312, have signed up for the study.
PHAROS is being carried out by the Huntington Study Group, a non-profit, cooperative group of Huntington's disease experts from medical centers throughout North America, Europe and Australia who are dedicated to improving treatment for persons affected by the disease. The group is based at the University of Rochester Medical Center. More information is available at www.Huntington-Study-Group.org.
The study is funded primarily by the National Institutes of Health (National Human Genome Research Institute at the National Institute of Neurological Disorders and Stroke) and the High Q Foundation, with support from the Huntington's Disease Society of America, the Huntington Society of Canada, the Fox Family Foundation, and the Hereditary Disease Foundation.