Research Highlight December 01, 2014

New guide for researchers aims to enhance reproducibility in Huntington's research


CHDI Foundation, The Jackson Laboratory and PsychoGenics Inc. have developed a new field guide for researchers studying Huntington's disease. The guide provides detailed information on the range of different Huntington's mouse models available, as well as guidance on study design to optimize results and their reproducibility.

Written by scientists for scientists, this extensive guide is intended to accelerate the development of treatments and improve the translation of results into the clinic.

In the twenty years since the identification of the Huntington's disease mutation — an unstable trinucleotide repeat expansion — many models for the disease have been engineered. Similar to human patients of Huntington's disease, these models vary in the length of the repeat expansion they carry, and consequently also exhibit differences in the onset, severity and progression of the disease. This variation complicates research into treatments, and presents challenges in translating results to a broader population.

Available mouse models were engineered via different methods, are on a variety of genetic backgrounds, and have documented variations in their sensitivity to environmental factors. The Huntington's disease field guide discusses the advantages and disadvantages of the models available, and provides a broad understanding of the differences between them to help researchers identify the most appropriate model for their particular research question. The guide also lays out a framework for best practices in colony management and study design, as well as the presentation of results, to maximize reproducibility.

Enhancing the reproducibility of results has recently become a topic of many conversations within the scientific community. Research dollars go farther and discoveries occur at a faster pace if scientists can more reliably build on each other's work. CHDI Foundation, The Jackson Laboratory and PsychoGenics, Inc. hope researchers will use the guide to build a path for faster identification and testing of treatments for Huntington's disease.

What is Huntington's disease and what causes it?

Huntington's disease is an inherited neurodegenerative disease that is both progressive and fatal. Although only approximately 30,000 individuals in the United States have Huntington's disease, another 150,000 others have a 50 percent risk of developing the disease, and a risk of passing it on to their children. Symptoms can include cognitive and behavioral changes (such as depression and mood swings), uncontrolled movements in the fingers, feet, face or trunk, as well as balance problems. As the disease progresses, walking, speaking and swallowing abilities decline.

Huntington's disease results from an autosomal dominant mutation in a single gene on chromosome 4. The genetic mutation consists of an abnormal repeat of a single amino acid sequence (CAG) in the chromosome. This abnormal repeat can vary in repetition from several to dozens of times, and is unstable. The repeat can expand even further over time within the genome of one individual, or with each successive generation. The alteration in the DNA sequence caused by this repeat expansion leads to production of an abnormal protein, and subsequent disruption and degradation of the nervous system.