Polku Therapeutics' compound blocks memory loss after repeated mild traumatic brain injury in preclinical model

Helsinki, Finland – October 9, 2025

Unmet Need in Brain Trauma

Every year, approximately 60 million people worldwide sustain traumatic brain injuries. Even mild concussions — particularly when recurring — can lead to persistent cognitive impairment, dementia, psychiatric disorders, and potentially chronic traumatic encephalopathy (CTE). Currently, no approved drugs exist to prevent or mitigate the long-term consequences of head trauma.

Breakthrough Findings

New research has shown that mice subjected to five successive mild traumatic brain injuries developed substantial cognitive deficits three months after injury. When treated with Polku's proprietary PREP ligand immediately following each injury, the development of these deficits was completely prevented.

Further analysis revealed that PREP ligands reduced key markers of neuroinflammation and cellular senescence — processes associated with accelerated aging and neurodegeneration. The compounds also restored a critical synaptic plasticity regulator essential for memory and cognition that becomes dysregulated following brain trauma. Together, these combined mechanisms suggest PREP ligands can interrupt the early biological cascades that drive long-term damage from repeated head injury.

Towards Disease-Modifying Therapies

"This is the first evidence that a small-molecule PREP ligand protects against cognitive decline caused by repeated concussions," said Professor Timo Myöhänen, the study's senior author and co-founder of Polku Therapeutics.

The findings further extend Polku's PREP–PP2A modulator platform, which is currently being evaluated in Alzheimer's disease models and other neurodegenerative conditions.

Broad Implications

These findings open new therapeutic avenues for traumatic brain injury patients and at-risk populations, including athletes in contact sports, military service members, and others who experience repeated concussions.

Study Details

Citation: Uhari-Väänänen J, Eteläinen T, Zuo C, De Lorenzo F, Kilpeläinen T, Myöhänen TT. A prolyl oligopeptidase ligand blocks memory deficit in a repeated mild traumatic brain injury model. Experimental Neurology, 2025.

DOI: https://doi.org/10.1016/j.expneurol.2025.115454

About Polku Therapeutics

Polku Therapeutics is a Helsinki-based biotechnology company developing novel small-molecule therapies targeting the PREP–PP2A pathway for the treatment of neurodegenerative diseases.