Descripción del proyecto
Una nueva medicación para tratar enfermedades encefálicas devastadoras podría estar en el horizonte
Uno de los mayores obstáculos para la administración sencilla y eficaz de tratamientos al encéfalo es la barrera hematoencefálica (BHE), cuya función natural consiste en proteger el encéfalo de invasores extraños. Las uniones extremadamente estrechas entre las células epiteliales que recubren los vasos sanguíneos del encéfalo también pueden bloquear el paso de moléculas terapéuticas grandes. Este ha sido el caso de una proteína prometedora que podría proteger a las neuronas dopaminérgicas de la enfermedad de Parkinson y la esclerosis lateral amiotrófica. El proyecto financiado con fondos europeos FutureTrophicFactors posee una nueva variante de esa proteína que tiene efecto terapéutico y puede atravesar la BHE. Los científicos del proyecto prevén dilucidar los mecanismos de ambos procesos en cultivos celulares con el fin de allanar el camino para una terapia sistémica revolucionaria para tratar la neurodegeneración encefálica.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
00014 Helsingin Yliopisto
Finlandia