Horizon Discovery (LSE: HZD) (“Horizon”), 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.