Peptone’s TDP-43 program is advanced with Mayo Clinic and Prof. Leonard Petrucelli. See Partnering and Collaborations on the pipeline page for detail.
Lead Optimization
TDP-43 aggregation modulator
A small molecule that engages the disordered low-complexity domain of TDP-43 to hold it in soluble states and interrupt the aggregation seen across ALS and frontotemporal dementia.
- Target
- Modality
- Indication
- Stage
Target
TDP-43 is an RNA-binding protein with a long intrinsically disordered low-complexity domain. In disease it mislocalises from the nucleus and assembles into cytoplasmic aggregates, a pathology shared across most amyotrophic lateral sclerosis and a large fraction of frontotemporal dementia cases, which makes the disordered domain itself the object of therapeutic design.
Approach
Peptone profiles the transient contacts within the low-complexity domain that drive phase separation and aggregation, then designs binders that favour soluble, assembly-incompetent states while preserving the protein's normal RNA-processing role.
Preclinical
Biophysical and cellular assays confirm target engagement and read out reduced aggregation, guiding selection of a chemical series. Disease biology and mechanism-of-action studies are advanced with Prof. Leonard Petrucelli at Mayo Clinic.
Development Plan
The program is in lead optimization, where the chemical series is being refined using collaboration-backed proteinopathy models ahead of candidate selection.
Collaborations
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Mayo Clinic
Jacksonville, United States
Prof. Leonard Petrucelli
Chair, Department of Neuroscience
Advancing TDP-43 mechanism of action and proteinopathy biology with Mayo Clinic neurodegeneration research.
View collaboration -
UCPH
Copenhagen N, Denmark
Prof. Kresten Lindorff-Larsen
Professor of Computational Protein Biophysics, Department of Biology
Revealing rare, transiently structured states in disordered proteins through multithermal simulation and experimental reweighting.
View collaboration