- HDSA Research
- Grant Applications
Research News & Reports
- Raptor Pharmaceuticals Announces Phase 2/3 Clinical Trial Results with Cysteamine (RP103) in Huntington’s disease
- Results of Phase 2 HD prevention and biomarker study (PRECREST) using high-dose of creatine published
- NIH announces first funding opportunities for the BRAIN Initiative
- Teva Pharmaceutical Industries to Purchase Huntexil from Neurosearch
- Postcard from CHDI February 2011
- HD Insights Volume 3
- Auspex Pharmaceuticals Plans Phase III Clinical Trial for Chorea in HD Patients
Research News Archive
- GABA stell cells
- proteomic analysis
- Methylene Blue
- A New Gene Silencing Technique Enters the Pipeline
- Hayden Study NMDAR Memantine
- MermaiHD ACR-16 (Huntexil) Trial Results
- MermaiHD Data Adjustment
- SIRT2 inhibition not promising
- Ray Truant and Colleagues Publish Promising Findings
- Melatonin Delays Onset of HD in Mouse Model
- Track-HD Dec 2012 Announcement
- New Prion Research Focuses Attention on the UPR in HD
- CIRM Awards $18 Million to UC-Davis for HD Stem Cell Research
- ENCODE Study finds "genetic switches"
- Video Postcard from CHDI 2012 Conference
- Researchers Restore Neuron Function using iPSCs
- Lundbeck CHDI Collaboration
- Video Postcards from Prauge
- EHDN Nightly News
- HDL2 News Page
- Steven Hersch Interview
- Siena Biotech
- Prana Planning
- Mechanism Matters
- Toxic Protein Form
- Roche and ISIS form HD Alliance
- FDA Selects HD for Patient-Focused Drug Development
- ASO treatment delivered to Alzheimer's patients in Phase I Study
- Prana Completes Phase 2 Huntington's Disease Trial with PBT2
- Omeros Phase I OMS824 Trial Results Positive
- Pharmacological Treatment of Chorea in HD Clinical Practice
- Research Webinar Series
- Clinical Trials
- HDBuzz Research News
- HD Gene Symposium: 20 Years
- Therapies in Pipeline
- Research Conferences
- Scientific Advisory Board
- Research Pipeline
- Stem Cells
- HD Insights
- HD Glossary
- Links to Other Research
- Reports Library
- Research Investors Reports
TRACK-HD Identifies Candidate Biomarkers Based
on a Two Year Longitudinal Study
The TRACK-HD researchers. led by Dr. Sarah Tabrizi, have reported their second year results. TRACK-HD is a longitudinal biomarker study of premanifest and symptomatic Huntington’s disease patients. The goal is to find biomarkers which change before and after onset to be used in clinical trials for premanifest and symptomatic patients.
The pre-manifest gene carriers were divided into two groups at the median estimated number of years to onset. The formula used to estimate years until onset was the Langbehn formula also used in the Predict-HD study. The early stage group was divided into two based on their scores on the Total Functional Capacity Scale.
Data was collected at baseline, at one year, and at two years, from 117 premanifest gene carriers, 116 early symptomatic participants, and 116 control group members. A variety of measures were used, including imaging measures of brain atrophy, cognitive measures, and scales from the United Huntington’s Disease Rating Scale (UHDRS). The researchers looked for measures that would distinguish one group from another and which changed longitudinally.
The imaging measures were the most effective in the symptomatic HD groups with both whole brain and regional atrophy progressing longitudinally and correlating with accepted clinical measures of disease progression – the Total Functional Capacity and the Total Motor Score scales of the UHDRS. Cognitive decline as measured by the Single Digit Modality Test, Stroop word reading, and indirect circle tracing also progressed longitudinally and correlated with disease progression.
Striatal and total white-matter atrophy was the most effective measure for premanifest gene carriers, progressing longitudinally even in those estimated to be ten years or more from onset. Cognitive, motor, and occulomotor measures were not sensitive.
The identification and validation of biomarkers is very important to promoting the development and availability of treatments. Because HD is a slowly progressive disease, Phase III clinical trials of potentially disease modifying drugs take years, adding to the cost of trials and delaying the time needed before successful drugs can become available to patients. A valid biomarker could shorten the time necessary for trials and also help to identify which drugs should be taken from Phase II to Phase III (final) trials.
The HD pipeline of potential treatments continues to grow; with limited resources (money and patients willing to volunteer for trials) it becomes important to prioritize which drugs are tried first. Given the short time periods associated with Phase I and Phase II trials, clinical differences are not usually detectable so prioritizing is difficult. When researchers examine a number of potential differences after a Phase II trial looking for signals whether to proceed, false positives become likely, as was the case with Dimebon. A significant improvement in the Mini Mental States Exam following a Phase II trial was encouraging but Dimebon was later found ineffective in a Phase III trial.
It is also important to discover and validate biomarkers in premanifest HD patients so that they can participate in trials and drugs can be identified which delay or prevent onset. In addition, once treatments become available, biomarkers will also be helpful in determining when to start administering treatments.
More work needs to be done to validate these candidate biomarkers. TRACK-HD is ongoing but the research done so far represents a major step in the process.
Lead author, UCL Institute of Neurology, Professor Sarah Tabrizi comments: “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.”
She concludes: “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.”
University College London press release
Sarah J. Tabrizi, Ralf Reilmanm, Raymund A. C. Roos, Alexandra Durr, Blair Leavitt, Gail Owen, Rebecca Jones, Hans Johnson, David Craufurd, Stephen L Hicks, Christopher Kennard, Bernhard Landwehrmeyer, Julie C Stout, Beth Borowsky, Rachael I Scahill, Chris Frost, Douglas R. Langbehn, and the TRACK-HD investigators. “Potential endpoints for clinical trials in premanifest and early Huntington's disease in the TRACK-HD study: analysis of 24 month observational data.” The Lancet Neurology E-Pub on line, December 2, 2011.
- Marsha L. Miller, Ph.D., December 8. 2011