Development of a TDP43-targeting gene therapy for ALS

ALS is caused by the abnormal accumulation of a protein called TDP-43, inside motor neurons in the spinal cord and brain. We have identified a pathway in which healthy cells normally remove TDP-43 to prevent its accumulation. We have identified a key component of this TDP-43 clearance
pathway and have developed a way in which we can therapeutically deliver it to remove toxic TDP-43 from motor neurons. This involves the delivery of a therapeutic gene to overexpress the protective clearance pathway – this approach is called gene therapy. In this project, we will undertake preclinical evaluation of our new gene therapy in mouse models of sporadic ALS. Positive outcomes will provide important data to support translation of this gene therapy into future clinical trials.

We have established a feasible and realistic pathway for pharmaceutical development of this technology if this project is successful. We have comprehensive patent protection for the therapeutic use of our gene therapy to treat ALS. Strong pre-clinical outcomes from this project together with our patent and translation strategy, will make this technology attractive for pharmaceutical company investment (which is essential for any successful new drug to be developed) to take forwards into clinical trials.