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Horizon Discovery Partners with The Michael J. Fox Foundation to Introduce Novel Pre-Clinical Models for Parkinson

publication date: Nov 17, 2017
 | 
author/source: Horizon Discovery Group

Innovative and relevant models for understanding alpha-synuclein biology and Parkinson’s disease pathogenesis in vivo

horizonHorizon Discovery (LSE: HZD), a global leader in gene editing and gene modulation technologies, in partnership with The Michael J. Fox Foundation for Parkinson's Research (MJFF), today introduced two new gene knock-out and knock-in rat models for investigating the role of alpha-synuclein in brain function and Parkinson’s disease (PD) pathogenesis.

Alpha-synuclein (SNCA) is a major constituent of Lewy bodies, protein clumps that are the pathological hallmark of PD, and so is an important target for research into the onset and development of the disease. To support this work, Horizon has used its SAGEspeed® Custom Model Generation Platform to develop and launch two innovative models with genetic modifications of SNCA, creating both a knock-out of endogenous alpha-synuclein and a humanized A53T knock-in, which has been linked to early-onset PD. The A53T knock-in promises to be field-enabling. As the only model available that expresses humanized A53T alpha-synuclein driven by the endogenous promoter without endogenous rat alpha-synuclein expression, it is expected to provide unambiguous insights into the biological effects of the A53T mutation in human alpha-synuclein. 

This project builds on Horizon’s long-standing partnership with MJFF that aims to provide the most innovative and relevant pre-clinical models to the neuroscience research community. In addition, the availability of these two new rat models meets a key objective of the MJFF Parkinson’s Research Tools Consortium (www.michaeljfox.org/toolsconsortium), a partnership between MJFF and industry groups to develop new tools to address unmet challenges in PD research. Tools such as the new models from Horizon and MJFF meet critical needs for both academic and industry experts by deepening understanding of alpha-synuclein biology and PD etiology, and advancing treatments for Parkinson’s disease. MJFF is leveraging Horizon’s Sponsored Breeding Program to help ensure that these models are widely available to the broader research community, including both for-profit and not-for-profit organizations, at an affordable price. 

Previously, Horizon and MJFF have collaborated on the development of rat models containing mutations in leucine-rich repeat kinase 2 (LRRK2), Parkin (Park2), PTEN induced putative kinase 1 (PINK1) and DJ-1 (Park7), all of which have been implicated as causative for PD. These lines, which are currently being used in studies across the globe, have been extensively characterized. Phenotype data can be found on MJFF’s website, as well as in the many publications available on the Horizon website.

Dr. Darrin M Disley, Chief Executive Officer, Horizon Discovery, commented: “Animal models, particularly rat given its more physiologically relevant neurobiology, play a key role in understanding the molecular mechanisms that govern brain function and the development of neurological disease. We are deeply gratified to be able to continue to partner with the Michael J. Fox Foundation, deploying our leading gene editing platform to develop specialized in vivo disease models as an important part of their ground-breaking work.”

Nicole Polinski, PhD, associate director of research programs at The Michael J. Fox Foundation said: “Researchers rely on advanced research tools and pre-clinical models to understand underlying causes and mechanisms of Parkinson's disease and to develop effective treatments. When such tools are unavailable, investigators must often make their own, investing time and resources that would be better spent studying PD.The growing collection of in vivo models from Horizon and The Michael J. Fox Foundation highlights the ongoing commitment of both organizations to push the boundaries of science, advance Parkinson’s disease understanding and speed therapeutic breakthroughs.”


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