Gerold Schmitt-Ulms

Key facts

• Tanz Centre, University of Toronto: CJD Foundation grants for a brain-penetrant PrPC-lowering molecule and for PrP seeding in AD and CTE.
• 2024 grants: Kong (NPDPSC) ADAM8-based gene therapy; Schmitz (Goettingen) tear fluid diagnostic; Schmitt-Ulms (Toronto) small brain-penetrant molecule that reduces PrPC and mouse models of spontaneous prion emergence; Castilla (CIC bioGUNE) dominant-negative protein-based gene therapy; Aguzzi and Caredio (Zurich) GPNMB as therapeutic target; organoids from sporadic CJD donors (RML postdoc).
• 2025 grants include Block (Colorado State) PrP seeding in non-prion dementia; Castilla (CIC bioGUNE); Schmitt-Ulms (Toronto) PrP seeding in AD and CTE; MRC Prion Unit on cancer risk from reduced PrPC expression; copy number variants as phenotype modifier (NPDPSC); Public Health Agency of Canada and University of Manitoba; Llorens and Zerr (CIBERNED and DZNE).
• The 2024 grant, bridging the pre-clinical gap for a small brain-penetrant molecule that reduces PrPC, aims to test oral dosing in a prion mouse model and track brain lowering in blood white cells.
• His 2025 conference slides report KDC203 cutting PrPC by about 85 percent in cells at very low nanomolar levels and in guinea pig brain slices.
• The slides also report that most oral KDC203 is converted by gut bacteria into a weaker compound that does not cross the blood-brain barrier.
• A 2024 PLOS ONE update found brain PrPC not lowered in guinea pigs because brain compound levels were too low and stated the survival-model goal was not met.
• A 2022 preprint introduced the brain-penetrant lead and framed the case for lowering PrPC with a small molecule.

Timeline

1. 2022Brain-penetrant lead introduced.
2. 2024Grant awarded.
3. 2024PLOS ONE update.
4. 2025Slides presented.