Project description
A vaccine against ALS
Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that leads to loss of muscle control. Recent evidence indicates that a GGGGCC hexanucleotide repeat in the non-coding region of the C9orf72 gene is the most common genetic cause of ALS. This causes the formation of poly-glycine-alanine (poly-GA) aggregates in the brain cells responsible for ALS pathology. The EU-funded GA-VAX project aims to develop a poly-GA peptide vaccine as a treatment against ALS. Following encouraging preclinical results, researchers will develop a clinical vaccine and undertake all necessary toxicology and efficacy studies prior to conducting a clinical trial in ALS patients.
Objective
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.
Fields of science
- 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
Keywords
Programme(s)
- HORIZON.3.1 - The European Innovation Council (EIC) Main Programme
Funding Scheme
HORIZON-EIC - HORIZON EIC GrantsCoordinator
53127 Bonn
Germany