Rare Disease Report
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New Huntington's Disease Natural History Study Will Help in Designing Future Clinical Trials

JUNE 13, 2013

In this week’s The Lancet Neurology,  Tabrizi and colleagues  summarized their analysis of various outcome measures (some expensive, some not) that may help predict phenotypic progression in people with early stages of Huntington’s disease as well as  disease onset in patients with the huntingtin gene mutation. The  multicenter, longitudinal, natural history study, called the TRACK-HD study examining patients with early Huntington’s Disease and patients with the huntingtin gene mutation (but without showing symptoms yet). Patients were followed for 36 months and given a battery of tests to determine their prognostic values. The tests included MRIs, clinical, cognitive, quantitative motor, and neuropsychiatric assessments.  These parameters along with patient’s age, the CAG repeat length were examined in relation to disease onset and/or progression.

By following patients at the beginning of disease onset as well as before disease onset, the TRACK-HD study hoped to provide valuable insight into which testing pramaters are most valuable. And the results were very interesting. As expected, neuroimaging analysis found that changes in volume of the whole brain volume and  various basal ganglia areas had strong predictive value regarding disease progression.  Interestingly, some less expensive measures, such as speed tapping  or certain motor-cognitive measures such as the symbol digit modality test, indirect circle tracing annulus length, and spot the change in 5 sec test,  were also  good predictors of disease progression.  Not all tests were good predictors however and readers are strongly  encouraged to obtain a copy of the study to ascertain the tests that may or may not be helpful in assessing disease progression and onset.

In an interview accompanying the article, Dr. Tabrizi discussed  some interesting take home messages from the study. They included:

  • In patients with huntingtin gene mutation but will not show symptoms for another 10-15 years, there were very few test parameters that changed over the 36 months of observations. However, theses patients did show some changes in the neuroimaging parameters over the 36 month period and should be tested in more detail.
  • In patient with huntingtin gene mutation and who will show symptoms of the disease soon, there are significant changes in clinical and imaging parameters over the course of the 36 months . This information should be helpful in developing clinical trials for patients before symptoms appear. For example, tests of tongue muscle showed decline in function before any other clinical symptoms were present.
  • Once disease symptoms have begun, there are numerous baseline measures that predict disease progression (see discussion above). Dr. Tabrizi noted that one of the most interesting baseline scores that predicted disease progression was a patient’s apathy score. Currently there is no therapy for apathy but that cortical function was highly predictive of disease progression.

Huntington’s disease is a rare neurodegenerative disorder due to a CAG repeat expansion in the huntingtin gene. The disease causes rapid deterioration in many cortical areas, most notably in the basal ganglia that lead to progressive decline of motor and cognitive functions, as well as  neuropsychiatric disturbances. The disease often begins to present itself in young-middle aged adults (30 – 40 yrs old) and progresses rapidly. Huntington’s disease is an autosomal-dominant disorder and genetic testing is available.

Currently there are limited treatment options for patients with Huntington’s disease but numerous investigative drugs are in development that may benefit from the TRACK-HD study.

In a commentary of the study, Francis Walker from the Department of Neurology at Wake Forest Medical School eloquently wrote “Hippocrates is generally credited with recognising the importance of the timeline of disease evolution epitomised by the objective recording of daily findings and methods and terms such as chronicity, exacerbation, paroxysm, and crisis. Sarah Tabrizi’s team has provided a modernised and extended example of this practice, one that sets the standard for observational studies in other neurodegenerative diseases.”

For more information about Huntington’s disease, visit www.hdsa.org


Tabrizi SJ, Scahill RO, Owen G, et al. Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington's disease in the TRACK-HD study: analysis of 36-month observational data. The Lancet Neurol 2013;12(7):637-49.

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