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Development of BMP2 Neurotrophic Therapy for Parkinson’s Disease

Projektbeschreibung

Neuer neurotropher Faktor für Parkinson-Krankheit

Von der Parkinson-Krankheit sind weltweit millionenfach Menschen betroffen, und diese Zahl wird sich angesichts der alternden Bevölkerung bis 2030 schätzungsweise verdoppelt haben. Trotz jahrelanger Forschung gibt es noch keine Therapie für die Parkinson-Krankheit. Das EU-finanzierte Projekt BMPARK untersucht das Potenzial des knochenmorphogenetischen Proteins 2 (BMP2) als ein neurotropher Faktor zum Schutz dopaminerger Neuronen im Hirn von Parkinson-Patienten. Anhand eines Rattenmodells der Krankheit wird das Forschungsteam die Wirksamkeit des knochenmorphogenetischen Proteins 2 auf die Eindämmung des fortschreitenden Verlusts dopaminerger Neuronen und bei der Verbesserung der motorischen Funktion wissenschaftlich beurteilen. Die Ergebnisse des Projekts werden die Wirkungsweise des knochenmorphogenetischen Proteins 2 entschlüsseln und zur zukünftigen Entwicklung klinischer Strategien in Bezug auf die Parkinson-Krankheit beitragen.

Ziel

Parkinson’s Disease (PD) is a progressive neurodegenerative disease. PD affects more than 6 million people worldwide while 1.2 million people have PD in Europe. For the European economy PD has a total socioeconomic cost of €13.9 billion per annum. With the aging demographic the number of individuals affects by PD are projected to double by 2030 highlight the need for disease modifying therapies. The neuropathological hallmarks of PD are the progressive loss of dopaminergic neurons in a region of the brain known as the substantia nigra in the midbrain, and the accumulation of intraneuronal inclusions called Lewy bodies and lewy neurite that consist predominantly of a protein called α-synuclein. Despite over half a century of investigation, there is no disease modifying therapy for PD. I propose that a protein called bone morphogenetic protein (BMP)2 can protect midbrain dopaminergic neurons in the PD brain. BMP2 is distinct from other neurotrophic factors used in the clinical trials to date in that it has a different signalling mechanism that can be targeted to protect dopaminergic neurons. Here I will assess the neuroprotective efficacy of viral vectors carrying the BMP2 transgene in the rat α-synuclein model of PD. I will determine if this molecular therapy can protect dopamine neurons and their axons against α-synuclein induced degeneration to maintain brain dopamine levels and improve motor function. To do this, I will use a multidisciplinary approach which will be paralleled by intensive training and career development opportunities to enable me to make a transformative contribution to knowledge and to achieve professional maturity and independence. In this way, this work has direct relevance for the future development of neurotrophic factors for clinical use in PD and the extensive dissemination and communication plans to target all stakeholders will ensure both societal and scientific impact in an European context and also for individuals with PD.

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Koordinator

UNIVERSITY COLLEGE CORK - NATIONAL UNIVERSITY OF IRELAND, CORK
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Region
Ireland Southern South-East
Aktivitätstyp
Higher or Secondary Education Establishments
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