Descripción del proyecto
Una vacuna para prevenir dos trastornos neurodegenerativos letales
Las enfermedades neurodegenerativas se caracterizan por la degeneración progresiva de la estructura y el funcionamiento del sistema nervioso, y suelen conllevar una pérdida debilitante y grave de las capacidades sociales, cognitivas y motoras. Dos ejemplos de ellas son la esclerosis lateral amiotrófica (ELA) y la demencia frontotemporal (DFT). La ELA, una enfermedad de las motoneuronas que impide los movimientos voluntarios, no tiene cura y en la actualidad carece de un tratamiento eficaz. Su progresión puede resultar en la pérdida de la capacidad de hablar, comer, moverse o incluso respirar. La DFT es un grupo de trastornos encefálicos que afectan a la personalidad, el comportamiento y el lenguaje. Un porcentaje pequeño de los casos de ELA y DFT comparten un defecto genético y el proyecto DPR-VAX, financiado con fondos europeos, ha desarrollado una vacuna específica para estas proteínas defectuosas. El proyecto recopila datos para ayudar a una comercialización rápida de esta vacuna que podría salvar vidas y reducir sustancialmente los costes sanitarios.
Objetivo
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.
Ámbito científico
- 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
Palabras clave
Programa(s)
Régimen de financiación
ERC-POC - Proof of Concept GrantInstitución de acogida
53127 Bonn
Alemania