TDP-43
Mayo Clinic and Leonard Petrucelli
Advancing TDP-43 mechanism of action and proteinopathy biology with Mayo Clinic neurodegeneration research.
- TDP-43 proteinopathy
- ALS and frontotemporal dementia
- Cryptic exon biology
Why we partner
TDP-43 aggregation modulators must be judged against the real biology of ALS and frontotemporal dementia: nuclear loss of function, cytoplasmic aggregation, RNA splicing defects, and the biomarkers that report those states. We partner with Prof. Leonard Petrucelli at Mayo Clinic to deepen mechanism-of-action and disease biology understanding for Peptone's TDP-43 program in systems built for that pathology.
Scientific focus
Prof. Petrucelli leads neurodegenerative disease research focused on TDP-43 proteinopathy across ALS and frontotemporal dementia. His laboratory studies how TDP-43 mislocalisation impairs RNA processing, how cryptic exons and cryptic peptides report loss of splicing repression, and how aggregation and genetic lesions such as C9orf72 shape disease. That body of work defines the biological bar for any small molecule that claims to engage disordered TDP-43 productively.
What Peptone brings
Peptone brings a disorder-first approach to the TDP-43 low-complexity domain: ensemble measurement of the contacts that drive phase separation and aggregation, and synthetic small molecules designed to favour soluble, assembly-incompetent states while respecting the protein's normal RNA-processing role.
What we do together
The collaboration centres on mechanism of action in disease-relevant models: how Peptone compounds alter aggregation propensity, cellular TDP-43 behaviour, and readouts linked to splicing dysfunction and proteinopathy. Access to specialised neurodegeneration models and biomarker thinking lets us test biology that generic aggregation assays cannot resolve.
Therapeutic ambition
We collaborate to generate first-in-class TDP-43 drug candidates by combining Peptone chemistry with Mayo Clinic disease biology ahead of the field. The purpose is not breadth for its own sake. It is depth: understand how our compounds engage TDP-43 pathology, then advance only the molecules supported by that understanding.