GDNF MIMETICS

Small molecules activating RET for the treatment of Parkinson's disease

Coordinatore	HELSINGIN YLIOPISTO    more  Organization address address: YLIOPISTONKATU 4 city: HELSINGIN YLIOPISTO postcode: 14 contact info Titolo: Ms. Nome: Katariina Cognome: Vainio-Mattila Email: send email Telefono: +358 9 19140822 Fax: +358 9 19123008
Nazionalità Coordinatore	Finland [FI]
Totale costo	870˙268 €
EC contributo	870˙268 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2013-IAPP
Funding Scheme	MC-IAPP
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-11-01   -   2017-10-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	HELSINGIN YLIOPISTO  Organization address address: YLIOPISTONKATU 4 city: HELSINGIN YLIOPISTO postcode: 14 contact info Titolo: Ms. Nome: Katariina Cognome: Vainio-Mattila Email: send email Telefono: +358 9 19140822 Fax: +358 9 19123008	FI (HELSINGIN YLIOPISTO)	coordinator	440˙144.10
2	MOLCODE AS  Organization address address: AHTRI 8 city: TALLINN postcode: 10151 contact info Titolo: Mr. Nome: Vallo Cognome: Paal Email: send email Telefono: +372 53432844 Fax: +372 668 8646	EE (TALLINN)	participant	430˙123.90

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 Obiettivo del progetto (Objective)

'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.'