Development of BMP2 Neurotrophic Therapy for Parkinson’s Disease

Informazioni relative al progetto

BMPARK

ID dell’accordo di sovvenzione: 890290

DOI

10.3030/890290

Progetto chiuso

Data della firma CE 3 Marzo 2020

Data di avvio 1 Settembre 2020

Data di completamento 31 Agosto 2022

Finanziato da

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Costo totale

€ 184 590,72

Contributo UE

€ 184 590,72

Coordinato da

UNIVERSITY COLLEGE CORK - NATIONAL UNIVERSITY OF IRELAND, CORK
Ireland

Periodic Reporting for period 1 - BMPARK (Development of BMP2 Neurotrophic Therapy for Parkinson’s Disease)

Periodo di rendicontazione: 2020-09-01 al 2022-08-31

Sintesi del contesto e degli obiettivi generali del progetto

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.
The main research aim is to provide a rich source of new understanding regarding how BMP2 may be a novel therapeutic for PD. To achieve this, the specific Research Objectives (ROs) of BMPARK are:
To examine the therapeutic efficacy of AAV2-BMP2 on the survival, innervation and function of DA neurons in the α-synuclein rat model of PD.
To identify the downstream molecular pathways through which BMP2 promotes dopaminergic neuron survival and growth.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

Behavioural testing performed and analysed.
Immunohistochemistry analysis currently ongoing.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

Longitudinal behavioural testing revealed that 4 weeks after injection of AAV-αSyn there were significant impairments in contralateral paw use compared to the ipsilateral paw in the cylinder test. This indicated that there was some degree of nigrostriatal damage at the time of AAV-BMP2 delivery.

Longitudinal behavioural testing after AAV-BMP2 or AAV-Null (Cont) vector delivery, showed significant improvements in contralateral paw use after AAV-BMP2 compared to controls.

This is the first report showing that AAV-BMP2 can improve behavioural outcomes in the rat AAV-αSyn model of Parkinson’s Disease.

Behavioural analysis