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A generalizable pre-clinical research approach for orphan disease therapy

Chandree L Beaulieu1, Mark E Samuels2, Sean Ekins3, Christopher R McMaster4, Aled M Edwards5, Adrian R Krainer6, Geoffrey G Hicks7, Brendan J Frey5, Kym M Boycott18* and Alex E MacKenzie18*

Author Affiliations

1 Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada

2 Centre de Recherche du CHU-Ste-Justine and Department of Medicine, University of Montreal, Montreal, Canada

3 Collaborations in Chemistry, Fuquay Varina, NC, USA

4 Atlantic Research Centre, Dalhousie University, Halifax, NS, Canada

5 Structural Genomics Consortium, Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada

6 Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA

7 Manitoba Institute of Cell Biology, University of Manitoba, Manitoba, MB, Canada

8 Children’s Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, ON, K1H 8 L1, Canada

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Orphanet Journal of Rare Diseases 2012, 7:39  doi:10.1186/1750-1172-7-39

Published: 15 June 2012


With the advent of next-generation DNA sequencing, the pace of inherited orphan disease gene identification has increased dramatically, a situation that will continue for at least the next several years. At present, the numbers of such identified disease genes significantly outstrips the number of laboratories available to investigate a given disorder, an asymmetry that will only increase over time. The hope for any genetic disorder is, where possible and in addition to accurate diagnostic test formulation, the development of therapeutic approaches. To this end, we propose here the development of a strategic toolbox and preclinical research pathway for inherited orphan disease. Taking much of what has been learned from rare genetic disease research over the past two decades, we propose generalizable methods utilizing transcriptomic, system-wide chemical biology datasets combined with chemical informatics and, where possible, repurposing of FDA approved drugs for pre-clinical orphan disease therapies. It is hoped that this approach may be of utility for the broader orphan disease research community and provide funding organizations and patient advocacy groups with suggestions for the optimal path forward. In addition to enabling academic pre-clinical research, strategies such as this may also aid in seeding startup companies, as well as further engaging the pharmaceutical industry in the treatment of rare genetic disease.

Orphan disease therapy; Preclinical drug development; Generalizable screening methods; Translational toolbox