Project description DEENESFRITPL A novel medication to treat devastating brain diseases may be on the horizon One of the greatest obstacles to simple and effective delivery of treatments to the brain is the blood-brain barrier (BBB), whose natural function is to protect the brain against foreign invaders. The extremely tight junctions between the epithelial cells lining the brain’s blood vessels can also block the passage of large therapeutic molecules. This has been the case for a promising protein that could protect dopaminergic neurons in Parkinson’s disease and amyotrophic lateral sclerosis. The EU-funded FutureTrophicFactors project has a novel variant of that protein that has a therapeutic effect and can cross the BBB. Scientists plan to elucidate the mechanisms of both in cell cultures to pave the way towards a revolutionary systemic therapy for brain neurodegeneration. Show the project objective Hide the project objective Objective The prevalence of neurodegenerative diseases such as Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS) is growing rapidly due to an aging population and increased life expectancy. Current treatments for ALS and PD only relieve symptoms and cannot stop the progression of the disease, thus there is an urgent need for new therapies. Neurotrophic factors (NTFs) are secretary proteins that regulate the survival of neurons, neurite growth and branching. They have been explored as novel drugs for the treatment of ALS and PD but their efficacy in clinical trials is poor. CDNF is a protein with NTF properties that protects and restores the function of dopamine neurons in rodent and rhesus monkey toxin models of PD more effectively than other NTFs. CDNF is currently in phase 1/2 clinical trials on PD patients. Despite promising results with CDNF in animal models of PD, NTF and CDNF-based treatments have drawbacks. CDNF requires direct delivery to the brain through invasive surgery since, it cannot pass through the blood brain barrier (BBB). My recent discovery, however, may overcome this difficulty: I showed that a novel CDNF variant protects DA neurons in vitro and in vivo and that it efficiently enters DA neurons in culture. Furthermore, my data show the CDNF fragment can pass through the BBB as measured by 3 different methods and has a neurorestorative effect in a 6-OHDA toxin model of PD when administered subcutaneously. The ultimate goal of my research is to understand the mode of action and therapeutic effect of novel BBB penetrating CDNF-derived polypeptides in cultures of human induced pluripotent stem (iPS) cell-derived nerve cells from patients and in animal models of ALS and PD. The innovative aspect of this proposal is the new groundbreaking concept for treating neurodegenerative diseases – peripheral delivery of BBB penetrating peptides with trophic factor properties and the potential to treat non-motor and motor symptoms in ALS and PD patients. Fields of science medical and health sciencesclinical medicinesurgerynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineneurologyparkinsonmedical and health sciencesbasic medicineneurologyamyotrophic lateral sclerosis Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2018-STG - ERC Starting Grant Call for proposal ERC-2018-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Host institution HELSINGIN YLIOPISTO Net EU contribution € 1 497 597,00 Address YLIOPISTONKATU 3 00014 Helsingin Yliopisto Finland See on map Region Manner-Suomi Helsinki-Uusimaa Helsinki-Uusimaa Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 497 597,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all HELSINGIN YLIOPISTO Finland Net EU contribution € 1 497 597,00 Address YLIOPISTONKATU 3 00014 Helsingin Yliopisto See on map Region Manner-Suomi Helsinki-Uusimaa Helsinki-Uusimaa Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 497 597,00
