Projektbeschreibung
Impfstoff gegen ALS
Amyotrophe Lateralsklerose (ALS) ist eine fortschreitende Erkrankung der Motoneuronen, die zum Verlust der Kontrolle über die Muskeln führt. Jüngste Erkenntnisse deuten darauf hin, dass eine GGGGCC-Hexanukleotid-Wiederholung in der nicht kodierenden Region des C9orf72-Gens die häufigste genetische Ursache von ALS ist. Sie verursacht in den Gehirnzellen die Bildung von Poly-Glycin-Alanin-Aggregaten (poly-GA), die für das Krankheitsbild von ALS verantwortlich sind. Ziel des EU-finanzierten Projekts GA-VAX ist die Entwicklung eines poly-GA-Peptid-Impfstoffs zur Behandlung von ALS. Nach ermutigenden präklinischen Ergebnissen werden die Forschenden einen klinischen Impfstoff entwickeln und alle erforderlichen Toxikologie- und Wirksamkeitsstudien durchführen, bevor eine klinische Studie an von ALS betroffenen Menschen folgt.
Ziel
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.
Wissenschaftliches Gebiet
- 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
Schlüsselbegriffe
Programm/Programme
- HORIZON.3.1 - The European Innovation Council (EIC) Main Programme
Aufforderung zur Vorschlagseinreichung
HORIZON-EIC-2021-TRANSITIONOPEN-01
Andere Projekte für diesen Aufruf anzeigenFinanzierungsplan
HORIZON-EIC - HORIZON EIC GrantsKoordinator
53127 Bonn
Deutschland