Unlocking PSP Treatment Potential

The Challenge

Progressive supranuclear palsy (PSP) is a rare neurodegenerative disorder with no known cause or effective treatments. PSP is characterised by the aggregation of the protein tau in the brain, but the underlying mechanisms driving tau aggregation remain unknown.

Project Overview 

This project aims to:

• Identify the protein changes in human brain tissue that drive PSP.
• Use this knowledge to uncover new drug targets and biomarkers that support diagnosis and treatment efforts.

‍Project Outcomes

• Identify Enriched Proteins: Identify proteins enriched in the insoluble proteome in PSP human brain tissue.
• Identify tau Interactions: Identify proteins that interact with tau in PSP human brain tissue.‍
• Understand Mechanisms: Determine how new potential drug targets mechanistically drive PSP.

Key Highlights

The project has made strong progress, including the completion of a study comparing brain protein changes in PSP, Pick’s disease, and corticobasal degeneration, which has now been accepted for publication in Alzheimer’s & Dementia. This is the first time these diseases have been directly compared using human brain tissue. Work is ongoing on a second study using the same approach to analyse the insoluble proteome in PSP motor cortex.

A key finding so far is a new protein called sortilin, which the team plans to investigate how widespread this is in PSP and what role it may play in the disease. Additional results have identified proteins that interact with tau in PSP and control brain tissue. These findings are currently being assessed to prioritise validation studies and potential drug target candidates. A promising antibody has also been identified that detects phosphorylated tau in PSP brain tissue.

Further work is underway to explore how these discoveries could lead to new treatments.

Measuring Impact

Hearts and Minds measures its impact across six core categories as developed by the Association of Australian Medical Research Institutes. Key highlights include:

Advancing Knowledge

• Key presentations and publications: various presentations and publications arising from this work including one recently accepted in Alzheimer’s & Dementia: "Differences in the soluble and insoluble proteome between primary tauopathies".
• Awards: Dr Eleanor Drummond (Lead Researcher) received the 2024 Irene Mona Martin Award from the Australian Dementia Network in recognition of her “innovative contribution to dementia research as a mid-career researcher”.

Research Capacity Building

• Leadership: The two lead researchers on the project are women, showcasing diversity in research leadership.‍
• Supporting emerging researchers: Four early career researchers have contributed to the project to date, gaining valuable experience in neurodegeneration and proteomics research.

Health Impacts

• ‍Improve quality of life: Enhance the quality of life for people living with PSP by identifying potential treatments.

Economic Impacts

• Grant Award: A grant was awarded to a postdoc on the project to develop a high throughput assay that profiles tau aggregates in the PSP cell culture model.

Informing Decisions

• Future Research and Treatment: The findings from this study will help inform future research and treatment of PSP.

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By uncovering the protein changes and interactions that drive PSP, this project aims to pave the way for new treatments and improve the lives of those affected by this rare disorder.

‍Funding support from Hearts and Minds Investments, as nominated by Core Fund Manager, TDM Growth Partners.

This content was last updated in July 2025, for further information visit Brain and Mind Centre.