Peptone’s TDP-43 program is advanced with Mayo Clinic and Prof. Leonard Petrucelli. See Partnering and Collaborations on the pipeline page for detail.
Hit to Lead
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 at the hit-to-lead stage, where confirmed hits are being triaged and optimised into a lead series with collaboration-backed proteinopathy models.