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New pathway and small-molecule compounds for Parkinson’s disease therapy

Parkinson’s disease (PD) is a neurodegenerative disease with growing incidence. More than 10 million people worldwide are affected by this condition. In addition to decline in the patients’ quality of life, the economic burden of... ver más

31/08/2025

HELSINGIN YLIOPIST...

216K€

Presupuesto del proyecto: 216K€

Líder del proyecto

HELSINGIN YLIOPISTO No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

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Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-10-26

HORIZON-MSCA-2021-PF-01-01: MSCA Postdoctoral Fellowships 2021 ExpectedOutcome:

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2 Participantes

HELSINGIN YLIOPISTO

215.53K€ | Lider

MPG

N.D. | Participante

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Duración del proyecto: 34 meses Fecha Inicio: 2022-10-26
Fecha Fin: 2025-08-31

Líder del proyecto

HELSINGIN YLIOPISTO No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 216K€

Descripción del proyecto Parkinson’s disease (PD) is a neurodegenerative disease with growing incidence. More than 10 million people worldwide are affected by this condition. In addition to decline in the patients’ quality of life, the economic burden of PD is estimated to exceed 13,9 billion EUR in EU annually. Considering this, novel and more efficient therapeutic options are needed, as current PD treatments alleviate symptoms without stopping neurodegeneration and progression of the disease. Although the etiology of PD is unclear, degeneration of dopamine (DA) neurons has been shown to result from certain genetic mutations, toxins and pathological protein aggregation among others. Importantly, recent evidence points to decrease in mRNA methylation at adenosine N6 (m6A) in PD. Data also indicate that m6A reduction may induce DA neuron apoptosis. Prof. Mart Saarma and collaborators have discovered that m6A methylation is a crucial regulator of neuronal apoptosis. They developed novel m6A methyltransferase activators and demethylase inhibitors that potently enhance mRNA m6A levels. Importantly, preliminary data show that these compounds protect DA neurons from neurotoxin-induced death in culture at nanomolar concentration. Moreover, one compound tested thus far remarkably improves motor behavior, protects and regenerates DA neurons and their axons in rat PD model more potently than gold standard GDNF. Considering this, the current project aims to elucidate the mechanisms how m6A regulates DA neuron survival and axonal regeneration. We will identify for the first time the mRNAs with increased/decreased methylation at adenosine N6 that regulate the life and death of DA neurons, thereby potentially opening new directions in PD research. In addition, we aim to provide completely new lead molecules for PD treatment. In conclusion, the current project aims to broaden our understanding on the mechanisms of Parkinson’s disease and provide new drug candidates for novel PD therapeutic avenues.

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