Cel Parkinson’s disease (PD) is caused by degeneration and progressive loss of dopaminergic (DA) neurons of the substantia nigra. In Western countries more than 6 million people live with PD. Currently no cure for this disease is available, existing therapeutic strategies alleviate PD symptoms but do not influence its cause or in other words do not prevent or slow down degeneration of DA neurons. Glial cell line-derived neurotrophic factor (GDNF) is one of the few molecules able to protect and repair DA neurons in animal models of PD. GDNF protein and the related factor neurturin were tested in five clinical trials, but the results have been inconclusive. The pharmacokinetic properties of these proteins complicate their therapeutic development. They do not pass blood-brain-barrier (BBB). Moreover, these factors diffuse poorly from the site of injection.The purpose of current proposal is to combine expertises of the academic and industrial partner in the fields of computational/medicinal chemistry (industrial participant), molecular/behavioural neuroscience and neuropharmacology (academic participant) to develop small molecules passing BBB and efficiently protecting and repairing dopaminergic neurons in vivo. We have developed an initial set of hits that activate GDNF receptors that at 1-10 uM concentration protect and repair DA neurons in vitro. We plan to optimize existing molecules and develop new ones to achieve an active concentration in the range 1-10nM using rational drug design approaches and cell-based screening methods developed by us.Successful compounds will be tested and optimized for ADMET and pharmacokinetic properties and studied in rat models of Parkinson’s disease to determine their safety, efficacy and other pharmacological characteristics. The expected outcome of this project is generation of safe drug-candidates efficient against Parkinson’s disease manifestations in laboratory animals. Dziedzina nauki natural sciencesbiological sciencesneurobiologymedical and health sciencesbasic medicinemedicinal chemistrynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicinepharmacology and pharmacypharmacokineticsmedical and health sciencesbasic medicineneurologyparkinson Program(-y) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) FP7-PEOPLE-2013-IAPP - Marie Curie Action: "Industry-Academia Partnerships and Pathways" Zaproszenie do składania wniosków FP7-PEOPLE-2013-IAPP Zobacz inne projekty w ramach tego zaproszenia System finansowania MC-IAPP - Industry-Academia Partnerships and Pathways (IAPP) Koordynator HELSINGIN YLIOPISTO Wkład UE € 440 144,10 Adres YLIOPISTONKATU 3 00014 Helsingin Yliopisto Finlandia Zobacz na mapie Region Manner-Suomi Helsinki-Uusimaa Helsinki-Uusimaa Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Katariina Vainio-Mattila (Ms.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych Uczestnicy (1) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko MOLCODE AS Estonia Wkład UE € 430 123,90 Adres AHTRI 8 10151 TALLINN Zobacz na mapie Rodzaj działalności Private for-profit entities (excluding Higher or Secondary Education Establishments) Kontakt administracyjny Vallo Paal (Mr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych