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
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.
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.
Behavioural testing performed and analysed.
Immunohistochemistry analysis currently ongoing.
Immunohistochemistry analysis currently ongoing.
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.
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.