Wren announced today the presentation of preclinical data for its first-in-class, oral inhibitors of α-synuclein oligomer generation demonstrating potent inhibition of both oligomer production and aggregate formation in cell and mouse models used for studying Parkinson’s disease progression.
BOSTON, March 29, 2023 /PRNewswire/ -- Wren Therapeutics announced today the presentation of preclinical data for its first-in-class, oral inhibitors of α-synuclein oligomer generation demonstrating potent inhibition of both oligomer production and aggregate formation in cell and mouse models used for studying Parkinson’s disease progression. The data were presented in poster and oral presentations today at the International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders (AD/PD 2023) taking place from March 28–April 1 in Gothenburg, Sweden. “α-Synuclein oligomers are fleeting protein intermediates implicated in the molecular damage and cellular destruction that decimate dopaminergic neurons in Parkinson’s disease and other α-synucleinopathies. Unfortunately, their elusive, ephemeral physical nature makes them difficult to target using conventional drug discovery approaches, as well as to develop biomarkers to support clinical development,” said Bart Henderson, CEO of Wren. “We are taking a different approach to drug discovery, using biophysics to design landmark therapeutics that can address the urgent need for effective drugs for this rapidly expanding neurodegenerative disease. In parallel, we are advancing the latest biomarker technologies to guide preclinical and clinical development to increase the probability of clinical success. We are excited about our progress and the promising initial data we presented today for several oral, small-molecule oligomer inhibitors and for the biomarker technologies we are deploying to measure on-target efficacy in both preclinical and clinical studies.” The relatively recent understanding that α-synuclein oligomers resulting from errant protein folding are the toxic entities directly responsible for neurotoxicity in PD has defined a new approach to treating a central molecular cause of neurodegeneration in Parkinson’s disease. Yet characterizing and suppressing transient protein intermediates is one of the most challenging problems in drug discovery for scientists working with protein assembly reactions, because these protein forms are highly transient and cannot simply be put in a bottle and analyzed in isolation. Targeting the complex, highly interconnected process of α-synuclein formation in Parkinson’s disease requires a different approach to measure, assay, and analyze the proteins during their evolving assembly and disassembly, from their formation to their disappearance. This requires targeting a network of interactions that is a fundamentally different approach from conventional single-target drug discovery. Wren’s technology platform enables the analysis of the inhibition of the source mechanisms that produce oligomer intermediates in complex disease processes. It is a network-centric approach to enable the discovery of small molecules that can block their generation with specificity and precision. Today’s presentations are the first data Wren has presented publicly that demonstrate the therapeutic potential of a new class of oral, small-molecule therapeutics developed using this technology platform for targeting the fleeting intermediates at the core of neurodegeneration. Highlights of the presentations follow, and the posters are available on Wren’s website: https://www.wrentherapeutics.com/our-science/publications Poster #825 / On-Demand Oral Presentation OD188: “The selective detection of alpha-synuclein oligomers to analyze small molecule inhibitors of their formation for the treatment of Parkinson’s disease"* *Special thanks to Eisai, which collaborated with Wren in conducting some of these studies Summary and key findings:
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