Preclinical Alpha Synuclein Model Developed
Blog Nov 12, 2017 | by Adam Tozer PhD
In the race to develop drugs to treat neurodegenerative disorders, having a good pre-clinical disease model is crucial.
Horizon Discovery recently announced their partnership with the Michael J Fox Foundation and the development of their new rodent model of Parkinson's disease.
We spoke with Andrew Brown, Product Manager at Horizon Discovery, to find out more:
AT: What are the current challenges with Parkinson’s research?
AB (Andrew Brown): Researchers rely on tools, including pre-clinical models, to understand the cause and mechanisms underlying Parkinson's disease and to develop effective treatments. When such tools are lacking, investigators must often make their own, wasting time and resources that would be better spent studying Parkinson's disease. Many existing tools also may lack sufficient quality control data, are difficult to obtain by the broader research community, or may come with restrictive license terms and fees that hinder drug makers' ability to use them. Promoting the generation and availability of these critical research tools is a key way MJFF accelerates therapeutic development for Parkinson's patients.
AT: How will your new model help overcome these?
AB: One of the traditional approaches to understanding a gene’s function is to simply remove the gene and observe the results. By removing the gene, the protein for which the gene codes is not produced. In the knock-out (KO) model, the alpha-synuclein gene is removed from rats with abnormal alpha-synuclein production. MJFF also leveraged Horizon’s Custom Model Generation Service and CRISPR/Cas9 to insert the human genetic version of the gene into these rats, allowing researchers to study the human alpha-synuclein protein in a pre-clinical model.
AT: Do you have any groups working with the new model, if so, what has feedback been like from them?
AB: Since these models are brand new to the research market they have only been characterized on the genetic level showing that the genetic sequence is truly knocked out and that the human sequence has truly been inserted. Many academic and industry researchers are bringing these models in-house for further characterization.
MJFF generated these models through their Parkinson’s Disease Research Tools Consortium (www.michaeljfox.org/toolsconsortium), and members will support the characterization of these models. The Parkinson’s Disease Research Tools Consortium incorporates input and investment from industry partners, including AbbVie, Amicus, AstraZeneca, Biogen, Merck, Pfizer and UCB, to develop pre-clinical tools.
AT: Do you have any other projects in the pipeline with MJFF?
AB: Discussions on future collaborations between MJFF and Horizon are ongoing. MJFF and Horizon share a commitment to drive tool development and accelerate Parkinson’s research. To that end, future projects may include generation of new pre-clinical models and expansion of cell line work.
AT: Is Horizon developing other models for different neurological diseases?
AB: Horizon has an extensive catalog of pre-clinical models involving Parkinson’s, Autism, and Alzheimer’s. See below or visit the full catalog list at www.horizondiscovery.com/in-vivo-models/knockout-rats/all-products
Parkinsons – Lrrk1, Lrrk2, Lrrk1/Lrrk2, Pink1(Park6), Park2(Parkin), Park7(DJ-1), Alpha-Synuclein, and Alpha-Synuclein A53T
Autism – Nlgn3, Fmr1, Nrxn1, Pten, mGluR5, MeCP2, Cntnap2, and MET
Alzheimer’s – ApoE, hApoE2, hApoE3, hApoE4, APP, and Bdnf
Optogenetics/Cre/Reporters – Halorhodopsin, Channelrhodopsin, 5Ht3a-Cre, CamkIIa-Cre, DAT-Cre, NPY-Cre, PV-Cre, Sst-Cre, Th-Cre, Tph2-Cre, VGAT-Cre, VIP-Cre, and Td-Tomato