Descrizione del progetto
Un vaccino per prevenire due disturbi neurodegenerativi fatali
Le malattie neurodegenerative sono caratterizzate dalla degenerazione progressiva nella struttura e nella funzione del sistema nervoso. Esse conducono spesso alla perdita grave e debilitante di capacità motorie, cognitive e sociali: alcuni esempi sono la sclerosi laterale amiotrofica (SLA) e la demenza frontotemporale (FTD, Frontotemporal Dementia). Per la SLA, una malattia dei motoneuroni che compromette i movimenti volontari, non esiste una cura e attualmente nessun trattamento efficace. La progressione può portare a una perdita della capacità di parlare, mangiare, muoversi e addirittura respirare. L’FTD è un gruppo di disturbi cerebrali non comuni che colpisce la personalità, il comportamento e il linguaggio. Una piccola percentuale di casi di SLA e FTD condividono un difetto genetico comune: il progetto DPR-VAX, finanziato dall’UE, ha sviluppato un vaccino che colpisce queste proteine difettose. Il progetto sta raccogliendo i dati per supportare un percorso rapido di commercializzazione di questo vaccino che potrebbe salvare vite e ridurre notevolmente i costi legati all’assistenza sanitaria.
Obiettivo
Neurodegenerative diseases are triggered by protein aggregation in the CNS, but developing therapies has been challenging. Since key disease mechanisms change during disease progression, halting further neuron loss has not been achieved and may not even improve the symptoms and survival. Causal therapy is most realistic for monogenic disease variants.
About 10% of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) cases are caused by repeat expansion in the C9orf72 gene. We have shown that the expanded repeat is translated into multiple aggregating dipeptide repeat (DPR) proteins. Poly-GA, the most abundant DPR species, is a key driver of downstream pathology. A poly-GA vaccine reduces aggregates and almost completely prevents motor deficits in our mouse model. With additional validation and safety experiment we will generate a pharma-ready data package for rapid preclinical and clinical devel-opment of the vaccine as first-in-class drug for prevention of ALS and FTD in C9orf72 carriers.
The parallel development of suitable biomarkers to show clearance of DPR aggregates in vivo will greatly accelerate clinical trials. Thus, we will optimize our published immunoassays to allow more sensitive detection of DPRs in patient CSF. Moreover, we will develop our patented DPR monoclonal antibodies into a PET tracer.
The solid data package is complemented by internal and external expertise in business development and regulatory affairs to shape an attractive business proposition and create value. ERC-PoC funding will allow us to present the opportunity to potential partners in large pharmaceutical companies and reputable venture capitalists for licensing or spin-off generation. Another proven strategy in the rare disease space would be collaboration with patient organizations to fund initial clinical trials. Preventing fatal ALS and FTD using vaccination in C9orf72 mutation carriers would be cost-effective for society and a blessing for affected families.
Campo scientifico
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines
- medical and health sciencesbasic medicineneurologydementia
- medical and health sciencesbasic medicinepathology
- medical and health sciencesbasic medicineneurologyamyotrophic lateral sclerosis
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-POC - Proof of Concept GrantIstituzione ospitante
53127 Bonn
Germania