E1(115368), ALPHACVAC, Redoxis

Purpose and goal:

Within this project (ALPHAVAC) we want to develop a treatment for the autoimmune disease ALS. We will construct RNA replicates to immunize mice with primary self-antigen (pSAgs) and thereby induce a model for the disease. In the next step, we will use Armana´s established platform for developing hereditary treatments where one restores tolerance to pSAgs and stops the autoimmune reaction.

Our hope is that this will cure disease and that we can get data that supports the effect of such a type of treatment as well as a new model for validation of new drugs. Expected results and effects:

In this project, we aim to develop the first curative ALS tolerance induction therapy. We will do so by developing a first-of-its-kind inducible ALS mouse model generated through a novel immunisation approach using Alphaviral RNA replicon-based antigen delivery. The main result of this project will be a curative ALS therapy that restores immune tolerance to the pSAg of ALS as validated in this project.

In addition, the project will generate new preclinical models for evaluation of therapies and proof of concept of a platform that have the potential also to be used in other conditions. Approach and implementation:

In the fist step, we will develop an inducible ALS mouse model using self-amplifying Alphaviral RNA replicons expressing candidate pSAgs. Once we have a model, well representing the human disease we will

deploy Amarna’s proprietary SVec viral gene delivery vector technology to develop and preclinically test an ALStherapy based on pSAg expression to induce an immune tolerance response that will stop the autoimmune motorneuron destruction. We will test the therapy’s in vivo efficacy in the newly developed inducible ALS mouse modeland compare it with currently used genetic ALS models.