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POLYMND: Polyamine dysregulation in Motor Neuron Disease as a targetable driver of astrocyte–neuron dysfunction

Project description

Restoring metabolic balance in ALS

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease associated with progressive muscle paralysis. While research has focused primarily on the motor neurons that die in ALS, growing evidence implicates astrocytes, support cells that normally protect neurons in the brain and spinal cord. With the support of the Marie Skłodowska-Curie Actions programme, the POLYMND project investigates whether disrupted polyamine metabolism in astrocytes drives neuronal damage in ALS. Using human stem cell-derived brain organoids from ALS patients, researchers will characterise how polyamine imbalance contributes to disease. Moreover, they will evaluate whether restoring balance using the naturally occurring polyamine spermidine can rescue disease-related cellular damage. The project findings may provide important insights into ALS and open new therapeutic avenues.

Objective

Every 45 minutes, someone in Europe dies from amyotrophic lateral sclerosis (ALS), a fatal disease that causes progressive muscle weakness, paralysis, and, eventually, death. With no cure available, there is an urgent need to explore new mechanisms and human-relevant models that could inform treatments. While most research has focused on the nerve cells, called neurons, that die in ALS, growing evidence suggests that other cells in the brain and spinal cord, particularly astrocytes which normally help and protect neurons, may actually contribute to their loss.

This project will investigate whether a chemical imbalance in astrocytes plays a hidden but important role in ALS, a fresh but well-grounded concept. Specifically, I will focus on polyamines, small molecules that are vital for healthy brain function, including cell stress responses and communication between cells. In ALS, astrocytes may lose control over polyamine levels, turning a helpful process into a harmful one that damages neurons. The research aims to dissect the cell-type-specific role of polyamine metabolism in ALS pathogenesis and to test whether restoring polyamine balance can rescue disease-related phenotypes.

To explore this, I will use stem cell technology to create miniature 3D human brain-like structures (organoids) from the cells of people with ALS. This will allow me to study how astrocytes malfunction in ALS, how polyamine metabolism is disrupted, and whether spermidine, a naturally occurring polyamine found in certain foods, can restore balance and reduce cellular damage. By uncovering and targeting a hidden metabolic weakness in ALS, this research could open the door to new therapies that aim to slow disease progression and preserve the cells and connections that keep people moving, speaking, and living.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Net EU contribution
€ 276 187,92
Address
TRINITY LANE THE OLD SCHOOLS
CB2 1TN CAMBRIDGE
United Kingdom
Region
East of England East Anglia Cambridgeshire CC
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data