Yeast-based neurodegeneration drug discovery platform
undisclosedplatform · medium · Mon Jun 06 2022 00:00:00 GMT+0000 (Coordinated Universal Time)
Use yeast-based research approaches to understand neurodegenerative disease biology and identify potential brain-drug candidates.
Disease-biology and drug-discovery platform using yeast as an experimental model system for neurodegenerative disease mechanisms.
Yumanity's research assets and discovery-stage product candidates were planned for sale to Janssen in 2022 as part of the company's wind-down and reverse merger plan.
YTX-7739 SCD inhibitor program
phase 1drug program · high · Mon Jun 06 2022 00:00:00 GMT+0000 (Coordinated Universal Time)
Develop a brain-penetrant stearoyl-CoA desaturase inhibitor for Parkinson's disease and related alpha-synucleinopathies by reducing alpha-synuclein toxicity and pathological lipid biology.
Small-molecule SCD inhibition; pharmacology tested in cell-based alpha-synuclein assays, patient-derived neurospheres, rat and monkey PK/PD studies, and alpha-synuclein mouse models.
YTX-7739 had entered Phase 1 clinical trials and was included among Yumanity assets planned for sale to Janssen for $26 million in cash on 2022-06-06.
Preclinical studies reported blood-brain-barrier penetration, dose-dependent brain pharmacodynamic effects, reduced fatty-acid desaturation, decreased alpha-synuclein-mediated neuronal death, reduced pathological pS129/PK-resistant alpha-synuclein, and prevention of progressive motor deficits in PD-like mice.
Alpha-synuclein iPSC inclusionopathy screening models
exploratoryplatform · medium
Create screenable human CNS inclusionopathy models for functional genomic analysis and drug development in proteinopathies such as alpha-synucleinopathies.
iPSC-derived CNS cells engineered with piggyBac or targeted transgenes, alpha-synuclein mutant expression, or exogenous fibril seeding to induce trackable inclusions at brain-like expression levels; single-inclusion tracking and proteome-scale genetic and physical interaction screens.
Published rapid iPSC inclusionopathy models in 2024.
The models identified multiple alpha-synuclein inclusion classes, including neuroprotective p62-positive inclusions and neurotoxic lipid-rich inclusions, and nominated RNA-processing and actin-cytoskeleton proteins such as RhoA as candidate toxicity modifiers.
Automated longitudinal single-cell neuron survival assay for synucleinopathy
exploratoryplatform · medium
Automate assessment of human neuron survival and health for small-molecule screening in synucleinopathy and other neurodegenerative diseases.
Automated neuron detection algorithms using BioStation CT live imaging and CL-Quant software to longitudinally track iPSC-derived neurons overexpressing A53T alpha-synuclein, with readouts including survival, neurite length, and neurite node number.
Published automated algorithm workflow in 2023.
The automated method measured alpha-synuclein A53T-associated neuronal death with similar accuracy and improved consistency compared with manual counting, shortened analysis time, and detected BDNF neuroprotective effects.
Patient-derived 3D cortical neurosphere Parkinson's disease model
exploratoryresearch program · medium
Model Parkinson's disease mechanisms in patient-derived iPSC cortical neurospheres to support preclinical evaluation of disease-relevant pathology and therapeutic candidates.
Three-dimensional cortical neurosphere cultures derived from Parkinson's disease patient iPSCs with SNCA A53T mutation or SNCA multiplication, compared with isogenic controls and characterized by qPCR, Western blotting, immunofluorescence, fatty-acid profiling, and alpha-synuclein pathology readouts.
Published patient-derived 3D cortical neurosphere model data showing disease-relevant fatty-acid and alpha-synuclein phenotypes.
Differentiated and aged neurospheres showed altered fatty-acid profiles and elevated total and pathogenic phospho-alpha-synuclein in A53T and SNCA triplication lines versus isogenic controls.