Descripción del proyecto
Una vacuna contra la esclerosis lateral amiotrófica
La esclerosis lateral amiotrófica (ELA) es una enfermedad progresiva de las neuronas motoras que conlleva la pérdida del control muscular. Pruebas recientes sugieren que la causa genética más común de la ELA es la repetición de hexanucleótidos GGGGCC en la región no codificante del gen C9orf72, que provoca la formación de agregados de poliglicina-alanina (poliGA) en las neuronas responsables de las alteraciones anatomopatológicas en la ELA. El objetivo del proyecto GA-VAX, financiado con fondos europeos, es desarrollar una vacuna peptídica poliGA como tratamiento contra la ELA. Tras resultados preclínicos alentadores, los investigadores desarrollarán una vacuna clínica y realizarán todos los estudios de toxicología y eficacia necesarios antes de realizar un ensayo clínico en enfermos de ELA.
Objetivo
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is triggered by protein aggregation in the brain and spinal cord motor neurons that leads to respiratory failure within 2-5 years. The best available drug extends life by ~3 months. ALS strikes about 1 in 500 people mostly for unknown reasons, but 5-10% of cases in Caucasians are caused by a mutation in the C9orf72 gene. We have shown that this mutation leads to expression of large aggregating poly-Glycine-Alanine (poly-GA), which triggers downstream pathology. We developed a poly-GA peptide vaccine that reduces aggregates and largely prevents motor deficits in a mouse model. When starting vaccination in already symptomatic mice, our vaccine reduces neuronal damage to a similar extent. Since regular lifelong vaccination is required to maintain sufficient antibody levels, GA-VAX is an attractive business case in the orphan disease space with ~2500 prevalent C9orf72 ALS cases in the US, DE, IT, FR, ES, UK. ~9000 mutation carriers at risk to develop disease within 10 years could benefit even more from our approach. A joint venture established by Intravacc and DZNE will bring together the right resources to advance this promising treatment approach towards clinical evaluation. Intravacc contributes know-how for production and clinical development of peptide/carrier conjugate vaccines, DZNE provides in depth knowledge of disease pathology as well as all necessary model systems and assays. Together we will setup GMP manufacturing for the antigen and conduct pivotal toxicology and efficacy studies in animals in accordance with regulatory requirements by EMA and FDA. This will allow us to compile a clinical trial application in C9orf72 ALS patients. In addition, we will use this data-package to raise capital for the phase 1 trial from a patient organization or investor for further de-risking or, preferentially, directly partner with a larger pharma company to bring GA-VAX to the market.
Ámbito científico
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines
- natural sciencesbiological sciencesgeneticsmutation
- medical and health sciencesbasic medicinepathology
- medical and health sciencesbasic medicinetoxicology
- medical and health sciencesbasic medicineneurologyamyotrophic lateral sclerosis
Palabras clave
Programa(s)
- HORIZON.3.1 - The European Innovation Council (EIC) Main Programme
Convocatoria de propuestas
HORIZON-EIC-2021-TRANSITIONOPEN-01
Consulte otros proyectos de esta convocatoriaRégimen de financiación
HORIZON-EIC - HORIZON EIC GrantsCoordinador
53127 Bonn
Alemania