Description du projet
Des traitements innovants pour traiter les maladies cérébrales dévastatrices se profilent à l’horizon
L’un des plus grands obstacles à l’administration de traitements simples et efficaces au cerveau est la barrière hémato‑encéphalique (BHE), dont la fonction naturelle est de protéger le cerveau contre les envahisseurs étrangers. Les jonctions très étroites entre les cellules épithéliales tapissant les vaisseaux sanguins du cerveau peuvent également bloquer le passage des grosses molécules thérapeutiques. Cela a été le cas pour une protéine prometteuse qui pourrait protéger les neurones dopaminergiques dans la maladie de Parkinson et la sclérose latérale amyotrophique. Le projet FutureTrophicFactors, financé par l’UE, possède une variante innovante de cette protéine ayant un effet thérapeutique et pouvant franchir la BHE. Les scientifiques prévoient d’élucider les mécanismes de ces deux protéines en cultures cellulaires pour ouvrir la voie vers une thérapie systémique révolutionnaire pour la neurodégénérescence cérébrale.
Objectif
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.
Champ scientifique
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
00014 Helsingin Yliopisto
Finlande