Three research teams will receive $350,000 each to advance tau-directed therapeutic strategies – spanning antisense oligonucleotides, targeted protein degradation and aggregation inhibition – through hit-to-lead and lead optimisation stages of drug discovery.
The Rainwater Charitable Foundation (RCF), one of the largest independent funders of neurodegenerative research, has announced more than $1m in grants through its 2026 Sprint to Lead (S2L) drug discovery programme.
The initiative will support three one-year research projects focused on targeting tau, a protein whose abnormal accumulation is associated with several neurodegenerative diseases. Each researcher will receive $350,000 to advance potential therapies through the hit-to-lead and lead optimisation stages of drug discovery.
Primary tauopathies include progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Pick’s disease and certain forms of frontotemporal degeneration (FTD). Despite advances in understanding how tau contributes to neurodegeneration, translating these findings into effective treatments is extemely challenging.
Despite remarkable innovations in our understanding of tau pathology, transforming insights into effective therapies remains one of the field’s greatest challenges. We believe that supporting bold, translational science at critical stages of drug discovery is imperative to help bridge that gap. Through Sprint to Lead, we aim to advance promising therapeutic approaches and bring renewed hope to people living with these devastating neurodegenerative diseases.”
Jeremy Smith, President, the Rainwater Charitable Foundation
Three approaches to targeting tau
One of the funded projects, led by Timothy Miller at Washington University School of Medicine in St Louis, will focus on restoring the balance between two forms of tau protein.
Some primary tauopathies are associated with an imbalance between three-repeat (3R) and four-repeat (4R) tau. Miller and his team are developing an antisense oligonucleotide (ASO) designed to reduce excess 4R tau while restoring a healthier balance between the two forms.
Previous preclinical studies demonstrated that the approach reduced excess 4R tau in disease-relevant mouse models and human neurons carrying disease-associated MAPT mutations, without reducing total tau in mice. The new funding will support further optimisation of the therapy ahead of potential clinical development.
A second project, led by Neil Vasdev at MedChem Imaging, will investigate whether harmful tau can be removed using compounds known as tau degraders.
Rather than simply blocking tau activity, these compounds are designed to bind the protein and recruit the cell’s natural protein-disposal machinery to break it down. The researchers will build on existing tau-binding compounds developed for positron emission tomography (PET) imaging, including one that has progressed into first-in-human imaging studies, with the aim to identify promising degrader candidates for future testing in animal models of primary tauopathies.
Meanwhile, Markus Zweckstetter and his team at brainQr Therapeutics are pursuing a preventative approach, developing small molecules that enter the brain and bind directly to tau to stop it converting into disease-associated forms.
The strategy aims to prevent pathological tau aggregation while preserving its normal interactions with microtubules, which are important for neuronal function. Building on an initial brain-penetrant compound, the team will optimise a new series of molecules to identify a lead candidate for further preclinical development.
Supporting the next stage of development
Through Sprint to Lead, the foundation aims to reduce the risks associated with early drug discovery and help promising candidates progress towards preclinical proof-of-concept studies and, where appropriate, future investigational new drug (IND)-enabling research.
The three projects represent different therapeutic strategies, from reducing excess tau and removing existing protein to preventing its conversion into pathological forms.
By supporting these approaches through critical stages of drug discovery, the programme aims to strengthen the pipeline of potential tau-targeting therapies and accelerate the development of treatments for conditions that currently have limited therapeutic options. The findings from the one-year projects could also help determine which candidates are suitable for further preclinical investigation and eventual clinical development.
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