Researchers have identified a set of objective, validated measures for evaluating new treatments for Huntington's disease (HD) in phase 2 and 3 clinical trials. According to the researchers, whose findings have been published Online first in The Lancet Neurology, the discovery should increase future new drug trial's chances of success to delay onset and reduce the severity of HD.
` Lead author, Sarah Tabrizi from University College London's Institute of Neurology in London, UK, explains:
"HD research is at a critical point, with new drugs in the later stages of development, and we propose a battery of assessments for use in clinical trials in people with early HD. Hypothetical treatment effects defined by slower longitudinal changes in these measures should be detectable over a realistic timescale with practical sample sizes. These new tools provide a key contribution towards our ultimate aim of establishing effective treatments for this devastating condition."
At present, clinical drug trials for HD treatments depend on the unified Huntington's disease rating scale (UHDRS) as the standard outcome measure, however, given that this scale only has limited reliability and sensitivity, it may not be sufficiently appropriate for measuring important changes in disease progression within a short time period. A more reliable testing method for potential treatments is therefore needed.
The TRACK-HD study was conducted to identify biomarkers that could be used in order to predict and more precisely measure the progression of HD. The researchers enrolled a total of 366 individuals from various countries (Canada, France, UK, Netherlands). Participants included 120 patients who were pre-symptomatic carriers of the HD gene mutation, 123 patients with early symptomatic HD, and 123 healthy controls. The researchers compared all participants in a series of techniques to assess their motor function, behavior, cognition, and advanced brain imaging.
At year-1, in January 2011, the researchers observed a wide range of changes of the neuroimaging and clinical measures in pre-symptomatic individuals, such as progressive reduction in white matter and whole-brain volume, as well as a decline in cognitive and motor function.
The 2-year follow up aimed to determine the performance of these measures with regard to tracking the progression of the disease on an annual basis and to calculate their impact to evaluate potential sensitivity and efficacy.
After 24-month, researchers discovered that brain imaging technique measures proved the most effective at detecting disease progression, with measures of brain atrophy increasing at a substantially higher, measurable rate in participants with no noticeable symptoms and those with early HD. They also provided the strongest outcome measure for both stages of the disease, however, according to the authors, it needs to be identified which measures have causal associations with functional decline.
Compared with the control group, the early Huntingdon disease group also showed a substantial deterioration in functional, cognitive, and motor function at the 2-year follow up. Traditional used UHDRS measures were outperformed by speeded tapping, which proved to be the most sensitive of the motor assessments.
In a concluding statement the researchers say:
"Future studies to investigate the validity of the markers as indicators of clinically meaningful and potentially reversible progression will advance the development of treatments for this devastating neurodegenerative disease."
Karl Kieburtz from the University of Rochester in New York, USA, states in a linked comment:
"With methods that have improved precision and predictability, sample size and trial duration estimates should decrease. These methods, coupled with trial designs created to identify and discard unhelpful interventions rapidly, should accelerate the process of finding effective treatments for HD and other neurodegenerative diseases."
Written by Petra Rattue