Descrizione del progetto
Una nuova medicina per il trattamento di devastanti malattie cerebrali potrebbe essere all’orizzonte
Uno dei maggiori ostacoli all’erogazione semplice ed efficace dei trattamenti al cervello è la barriera emato-encefalica (Blood-Brain Barrier, BBB), la cui funzione naturale è quella di proteggere il cervello da invasori esterni. Queste giunzioni estremamente strette tra le cellule epiteliali che ricoprono i vasi sanguigni del cervello possono inoltre bloccare il passaggio di grandi molecole terapeutiche. È il caso di una proteina promettente che potrebbe proteggere i neuroni dopaminergici nel morbo di Parkinson e nella sclerosi laterale amiotrofica. Il progetto FutureTrophicFactors, finanziato dall’UE, possiede una nuova variante di questa proteina che ha un effetto terapeutico ed è in grado di attraversare la BBB. Gli scienziati pianificano di chiarire i meccanismi di entrambi nelle colture cellulari per aprire la strada a una terapia sistemica rivoluzionaria per la neurodegenerazione cerebrale.
Obiettivo
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.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
00014 Helsingin Yliopisto
Finlandia