CurePSP and Rainwater Charitable Foundation Fund a Record Seven Studies on PSP and CBD

CurePSP has awarded its largest-ever class of Pathway and Pipeline Grants, funding seven studies on progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) at institutions across North America and Europe. The program gives early-career scientists seed funding — up to $100,000 per study — to pursue ideas too preliminary for larger grants, from basic tau biology to new diagnostic biomarkers. This year's projects, supported in part by a $300,000 contribution from the Rainwater Charitable Foundation (RCF), range from computer-vision tools that track motor symptoms to AI-designed molecules that target toxic tau structures. The funding will accelerate research toward earlier diagnosis and treatment for those living with PSP and CBD. Recipients emphasized the importance of working directly with families whose generosity makes their work possible. Dr. Zhengrong Zhang, a researcher at Mayo Clinic in Florida, pointed to the clinical roots of her project as a source of motivation.

“What makes this project especially exciting is that the biological signal we are investigating was identified directly from brain tissue donated by individuals with PSP and CBD,” said Dr. Zhang.

Learn more about this year's funded scientists and their research below:

Engineering Conformation-Specific De Novo Therapeutics Targeting PSP and CBD Tau Amyloid Strains

Dr. Nikolaos Louros of the University of Texas Southwestern Medical Center is using artificial intelligence to design molecules that can recognize and neutralize the specific abnormal tau structures found in PSP and CBD, without disrupting healthy tau. His team will design and computationally screen thousands of candidate molecules against brain tissue donated by patients, with the most promising candidates developed into “degraders” that tag toxic tau for removal by the cell's natural cleanup systems. The work aims to lay the foundation for precision therapies tailored to the exact structure of the disease-causing protein.

“This is early-stage research, but our goal is to create tools that can recognize the specific toxic protein structures driving these diseases and help move the field closer to targeted treatments,” Dr. Louros said.

Systematic Dissection of the Molecular Mechanisms Driven by Tauopathy Risk Gene KANSL1

Dr. Le Qi of the University of California Los Angeles is investigating a genetic variant that lowers the risk of PSP, CBD and related dementias. Her team discovered that a chromosomal inversion linked to reduced dementia risk gives rise to a novel fusion protein, KANSL1-LRRC37A, found only in people who carry the inversion. The study will map where this fusion protein sits in neurons, reduce its levels in neurons derived from people with and without the inversion and examine resulting changes in tau accumulation, cell death and gene expression. This research could reveal why the inversion is protective and point to new drug targets for PSP and CBD.

“We cannot effectively treat a disease we do not fully understand,” Dr. Qi said. “By decoding exactly how some individuals are naturally protected against PSP/CBD, we aim to turn that biological blueprint into real, targeted therapies that can stop these diseases in their tracks.”

Targeting ATP1B3 to Suppress EV-Mediated Tau Propagation in CBD and PSP

Dr. Zhang's project at Mayo Clinic Florida examines how tau spreads between brain cells inside extracellular vesicles (EVs) — tiny packages that can act as vehicles carrying harmful tau to neighboring cells. Her team identified a protein called ATP1B3 that binds to tau and helps load it into these vesicles, with elevated levels observed in CBD brains, suggesting it may play a central role in tau spread. The study will examine EVs carrying ATP1B3 from the brains of people with CBD and PSP to understand how they contribute to tau buildup and affect neuron health, and will test whether removing ATP1B3 from human neurons can reduce tau in vesicles, block its spread to other cells and protect brain cells. The work could point to new therapies that interrupt tau spread in these diseases.

“By identifying the molecular mechanisms that regulate this process, we hope to uncover new pathways involved in tau-driven neurodegeneration,” Dr. Zhang said. “These findings could provide a foundation for future studies aimed at developing biomarkers to track disease progression and therapies that interrupt the spread of pathological tau, ultimately moving the field closer to disease-modifying treatments.”

Computer Vision Biomarkers for Objective (Oculo-) Motor Assessment in PSP

Dr. Carla Palleis of LMU University Hospital in Munich is developing digital tools to measure the movement and eye movement problems that define PSP. Using simple video recordings, her team will apply computer vision technology to automatically track and score symptoms currently assessed through subjective clinical rating scales. The study will follow 40 people with confirmed PSP and 20 healthy individuals over 12 months, training computer models to detect subtle changes in disease progression and fall risk over time.

“Earlier recognition could lead to faster diagnosis, better access to expert care and more timely support for patients and their families,” Dr. Palleis said. “Our long-term vision is that this technology will eventually provide immediate, objective feedback on a patient's symptoms, helping non-specialists recognize signs of PSP/CBD sooner.”

Role of SLCO1A2 on Oligodendroglial Biology in PSP

Dr. John Zhou of Yale University is studying why oligodendrocytes, the brain cells responsible for producing myelin, are especially vulnerable in PSP. His team found that a PSP-linked mutation in the gene SLCO1A2 sharply reduces a transporter protein's presence on the cell surface, cutting oligodendrocytes' ability to take in bile acids and thyroid hormones essential for metabolism and myelin production. The study will examine how this mutation affects cellular energy production and tau accumulation, both in lab models and in human PSP brain tissue, to determine whether restoring these inputs can protect oligodendrocytes from damage.

“This is my first research award, and it represents an important milestone in my career,” Dr. Zhou said. “Early-career scientists are deeply committed to improving our understanding of PSP and CBD, and to translating that knowledge into meaningful progress toward better treatments.”

Mechanistic Modelling of PSP Tau Progression Using Spatial Transcriptomics

Dr. Patrick Cullinane of University College London is studying why PSP progresses so differently from person to person. His prior work found that the disease spreads through the brain along more than one path, producing distinct symptom patterns that often delay diagnosis. Using donated brain tissue and a technique called spatial transcriptomics, his team will map gene activity in astrocytes and microglia across brain regions and PSP subtypes, then link those patterns to where tau accumulates — work aimed at explaining regional vulnerability and pointing to new diagnostic markers and treatment targets.

“This project will help link patterns of tau pathology to the molecular features that make particular brain regions vulnerable,” Dr. Cullinane said. “I hope it provides a framework for defining biologically meaningful PSP subtypes that future biomarker and treatment studies can build on.”

To explore all of this year's Pathway and Pipeline Grant studies, click here.