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Dipeptide-Repeat Vaccine to prevent ALS and FTD in C9orf72 mutation carriers

Project description

One vaccine to prevent two fatal neurodegenerative disorders

Neurodegenerative diseases are characterised by progressive degeneration in the structure and function of the nervous system. They often result in severe and debilitating loss of motor, cognitive and social abilities: examples are amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). ALS, a motor neuron disease impairing voluntary movements, has no cure and currently no effective treatment. Progression can result in loss of ability to speak, eat, move and even breathe. FTD is a group of uncommon brain disorders affecting personality, behaviour and language. A small percentage of ALS and FTD cases share a common genetic defect: the EU-funded DPR-VAX project has developed a vaccine targeting these defective proteins. The project is collecting the data to support a speedy pathway to market for this vaccine that could save lives and reduce healthcare costs substantially.

Objective

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.

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-POC - Proof of Concept Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2019-PoC

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Host institution

DEUTSCHES ZENTRUM FUR NEURODEGENERATIVE ERKRANKUNGEN EV
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 150 000,00
Address
VENUSBERG-CAMPUS 1/99
53127 BONN
Germany

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Region
Nordrhein-Westfalen Köln Bonn, Kreisfreie Stadt
Activity type
Research Organisations
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Total cost

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Beneficiaries (1)

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