Projektbeschreibung
Neuartige Medikamente zur Behandlung verheerender Hirnerkrankungen in Sicht
Eines der größten Hindernisse, die einer einfachen und wirksamen Behandlung des Gehirns im Wege stehe, ist die Blut-Hirn-Schranke, deren natürliche Funktion darin besteht, das Gehirn vor fremden Eindringlingen zu schützen. Die extrem engen Verbindungen zwischen den die Blutgefäße des Gehirns auskleidenden Epithelzellen können gleichermaßen größere therapeutische Moleküle blockieren. Dieser Fall trat auch bei einem vielversprechenden Protein ein, das dopaminhaltige Neuronen bei der Parkinson-Krankheit und der amyotrophen Lateralsklerose schützen könnte. Das EU-finanzierte Projekt FutureTrophicFactors hat eine neuartige Variante dieses Proteins vorzuweisen, die eine therapeutische Wirkung hat und die Blut-Hirn-Schranke passieren kann. Das Forschungsteam plant, beide Mechanismen in Zellkulturen zu erkunden, um den Weg zu einer revolutionären systemischen Therapie der Neurodegeneration des Gehirns zu bereiten.
Ziel
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.
Wissenschaftliches Gebiet
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-STG - Starting GrantGastgebende Einrichtung
00014 Helsingin Yliopisto
Finnland