Closing the circle on Huntington’s disease

NEW YORK—Thomson Reuters has entered into a collaborationwith the CHDI Foundation to undertake a novel and holistic systems biologyinvestigation into Huntington's disease.

The collaborative project aims to create two new tools thatwill aid researchers in unlocking the uncommon but devastating neurologicaldisease. The first goal is the creation of causal network models for thedisease mechanisms of Huntington's disease. These will be based on CHDI's geneexpression data and modeled using Thomson Reuters' knowledge base andtechniques.

The second goal of the collaboration is to create a "highwaymap" of the numerous, interconnected pathways within the body as they relate toHuntington's disease. The effort will identify potential molecular targets forpharmalogical intervention and begin identifying the appropriate pathways toreach these targets within the human body.

This collaboration will constitute a long-term and holisticapproach in that it will begin with basic data collection, include hypothesisgeneration, and see the efforts through to trials in patients, which will thenlead to more and better data with which to continue the cycle and guide futuredevelopment of interventions.

"This may be the first time within the pharmaceuticalindustry that this fully integrated, complete, close-the-circle process hasbeen focused around a single disease," says Keith Elliston, vice president ofsystems biology at the CHDI Foundation.

"We traditionally look at pathways in Huntington's disease,"says Dr. Simon Noble, director of scientific communications at the CHDIFoundation. "We know a few pathways that are probably—pretty clearly—involved,but we need a better understanding of how one pathway affects another."

"We know the protein that causes the disease, but we can'tconnect the dots between the mutation and its manifestation," says Elliston."Our challenge is to follow the causal mechanisms upstream to where we canintervene."

Enter Thomson Reuters. Thomson Reuters' life sciencesdivision will bring to bear its expertise in understanding biological pathwaysand networks, causal reasoning techniques and advanced systems biologytechniques including disease reconstruction. As part of this collaboration, itwill develop 10 new disease pathology maps relating to Huntington's diseaseunder the guidance of CHDI.

"A systems biology approach will provide increasedunderstanding of the mechanisms of disease progression at a molecular level,and suggest possible new targets in biological pathways for therapeuticintervention to arrest, reverse or ultimately cure the disease," says JoeDonahue, senior vice president of life sciences at Thomson Reuters.

The results of this project will be made broadly availableto the research community, with the goal of enabling additional study anddevelopment of new therapies. The collaborators hope that this project and theknowledge base it generates will open doors and enable future advancements inHuntington's disease treatments, as well as additional collaborations amongmembers of the research community.

The CHDI Foundation is a privately funded, not-for-profitbiomedical research organization exclusively focused on and dedicated toHuntington's disease. Its goal is to facilitate the discovery and rapiddevelopment of new therapies and drug candidates to treat the disease. Itboasts a large volume of data and cell resources relating to Huntington'sdisease, as well as links to the patient population.

Thomson Reuters first became involved in Huntington'sdisease research via a partner-driven MetaMiner CNS Project through its legacyGeneGo business. A component of this project that focused on Huntington'sdisease ran from late 2009 through mid-2010. The project's aim was theannotation of biomarkers for Huntington's disease and the construction ofdisease-specific pathology maps to help provide an understanding of thebiological interactions that define the disease.

Huntington's disease is a devastating neuropsychiatricdisorder marked by cognitive decline and emotional disturbance. It oftenstrikes during the prime of life and becomes progressively more severe duringthe 15- to 20-year course of the disease.

Huntington's is something of an orphan disease. Its relativerarity has limited the size of the patient population, research community andpharmaceutical market. Researchers at CHDI believe, however, that Huntington'sdisease can be a model for better understanding other similar disorders aswell. Unlocking the pathways for Huntington's disease could have direct utilityin addressing other neuropsychiatric disorders such as Parkinson's disease.