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Novel blood-brain barrier permeable CDNF-derived therapeutic peptides for the protection and regeneration of dopamine neurons

Project description

Novel treatment for Parkinson's disease

Emerging evidence indicates that cerebral dopamine neurotrophic factor (CDNF), a polypeptide chain containing 161 amino acids, can reverse neurodegeneration in vitro and in vivo in animal models of Parkinson's disease (PD). It was successfully tested in in phase I-II clinical trials in PD patients. However, due to the blood-brain barrier, full-size CDNF must be delivered to the brain of PD patients through microsurgery. To overcome this problem, the EU-funded THERAPE project contributes to the development of short CDNF-derived peptides capable of penetrating through the blood-brain barrier and reaching the brain. These innovative peptides hold great promise for the treatment of PD as, through systemic delivery, they also have the potential to treat non-motor symptoms.

Objective

Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by the progressive loss of midbrain dopamine neurons that leads to the severe movement disorders and several non-motor symptoms. Available PD treatments do not provide long-lasting relief from the symptoms and do not slow down or stop the neurodegeneration.
Cerebral dopamine neurotrophic factor (CDNF) was shown to reverse the PD-associated neurodegeneration in vitro and in vivo in animal models. Currently, CDNF is tested in the phase I-II clinical trials in PD patients. Despite of the promising results, CDNF doesn’t pass through the blood brain barrier (BBB) and should be delivered to the brain of PD patients through the risky microsurgery. Thus, there is a great need for the CDNF variants that can penetrate through the BBB avoiding intracranial surgery. In addition, systemic delivery of BBB permeable CDNF would offer a possibility to treat non-motor symptoms.
Current proposal combines the cutting-edge molecular neurobiology and nanomedicine to develop the next generation CDNF-derived peptides that will be able to penetrate the BBB. For that 1) the length of CDNF will be reduced to enable penetration through the BBB, 2) CDNF fragment will be mutated to improve its stability in the blood and tissues and 3) CDNF fragment will be conjugated to nanoparticles to increase its stability and ability to penetrate the BBB. Our preliminary data showed the feasibility of this approach and holds great promises for the breakthrough in the treatment of PD. In addition, during the project applicant will be trained into independent group leader through the hands-on training in the top scientific laboratories and by managing the highly innovative research at the interface of different disciplines connecting three excellent scientists: Prof. Saarma, the world leading molecular neurobiology researcher, Prof. Laakkonen, the expert in homing peptides and Prof. Santos, the master of nanomedicine.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2018

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Coordinator

HELSINGIN YLIOPISTO
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 202 680,96
Address
FABIANINKATU 33
00014 HELSINGIN YLIOPISTO
Finland

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Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 202 680,96
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