Descrizione del progetto
Un vaccino contro la sclerosi laterale amiotrofica
La sclerosi laterale amiotrofica (SLA) è una malattia progressiva dei motoneuroni che provoca la perdita del controllo muscolare. Prove recenti indicano che una ripetizione esanucleotidica GGGGCC nella regione non codificante del gene C9orf72 rappresenta la causa genetica più comune della SLA. Ciò provoca la formazione di aggregati poli-glicilalanina (poli GA) nelle cellule cerebrali responsabili della patologia della SLA. Il progetto GA-VAX, finanziato dall’UE, intende sviluppare un vaccino a base di peptidi poli-GA come trattamento per la SLA. In seguito a risultati preclinici incoraggianti, i ricercatori svilupperanno un vaccino clinico e intraprenderanno tutti gli studi tossicologici di efficacia necessari prima di condurre la sperimentazione clinica sui pazienti affetti da SLA.
Obiettivo
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.
Campo scientifico
- 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
Parole chiave
Programma(i)
- HORIZON.3.1 - The European Innovation Council (EIC) Main Programme
Invito a presentare proposte
HORIZON-EIC-2021-TRANSITIONOPEN-01
Vedi altri progetti per questo bandoMeccanismo di finanziamento
HORIZON-EIC - HORIZON EIC GrantsCoordinatore
53127 Bonn
Germania