Summary
Mental health problems are a critical and ever-increasing burden to society. Psychiatric medications aim to adjust imbalances in synapse signaling, but often have only moderate-to-weak efficacy. Psychiatric medications aim to adjust imbalance in synapse signaling but often have only moderate-to-weak efficacy. The main challenge is that certain neuronal infrastructures for cognitive and emotional skills are secured with a rigid extracellular matrix known as the perineuronal net (PNN) that forms around neurons and locks the brain in a function state. Enzymatic interventions that can release the lock have been evaluated in mice, but they are not appropriate for translating into human therapeutics because they are invasive and prevent the reformation of PNN making the brain vulnerable. In the context of the ERC StG, we discovered that non-invasive external light entrainment at highly-selective 60-Hz enables microglia localized within the neuronal network to transiently remove PNN in a controlled and brain region-specific manner in both sexes with improved cognitive performances in mice. Thus, our discovery solves the urgent need for a targeted, non-invasive, non-pharmacological, therefore environmental-friendly therapeutic intervention. This ERC Proof-of-Concept will allow us to expand on our discovery and evaluate the therapeutic potential in a preclinical mouse model of anxiety disorder, post-traumatic stress disorder (PTSD). Our objectives are to identify at which stage of the fear memory formation 60-Hz entrainment shows the highest benefit, adjust treatment length and repetition frequency, and validate physiological parameters as a therapeutic success criterium. These insights will refine the first prototype development and set the therapeutic frame, which will both be critical to smoothen the transition into a clinical study post-ERC PoC, and will set the foundation for a spin-off company.
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| Web resources: | https://cordis.europa.eu/project/id/101138423 |
| Start date: | 01-03-2024 |
| End date: | 31-08-2025 |
| Total budget - Public funding: | - 150 000,00 Euro |
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Original description
Mental health problems are a critical and ever-increasing burden to society. Psychiatric medications aim to adjust imbalances in synapse signaling, but often have only moderate-to-weak efficacy. Psychiatric medications aim to adjust imbalance in synapse signaling but often have only moderate-to-weak efficacy. The main challenge is that certain neuronal infrastructures for cognitive and emotional skills are secured with a rigid extracellular matrix known as the perineuronal net (PNN) that forms around neurons and locks the brain in a function state. Enzymatic interventions that can release the lock have been evaluated in mice, but they are not appropriate for translating into human therapeutics because they are invasive and prevent the reformation of PNN making the brain vulnerable. In the context of the ERC StG, we discovered that non-invasive external light entrainment at highly-selective 60-Hz enables microglia localized within the neuronal network to transiently remove PNN in a controlled and brain region-specific manner in both sexes with improved cognitive performances in mice. Thus, our discovery solves the urgent need for a targeted, non-invasive, non-pharmacological, therefore environmental-friendly therapeutic intervention. This ERC Proof-of-Concept will allow us to expand on our discovery and evaluate the therapeutic potential in a preclinical mouse model of anxiety disorder, post-traumatic stress disorder (PTSD). Our objectives are to identify at which stage of the fear memory formation 60-Hz entrainment shows the highest benefit, adjust treatment length and repetition frequency, and validate physiological parameters as a therapeutic success criterium. These insights will refine the first prototype development and set the therapeutic frame, which will both be critical to smoothen the transition into a clinical study post-ERC PoC, and will set the foundation for a spin-off company.Status
SIGNEDCall topic
ERC-2023-POCUpdate Date
12-03-2024
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