UNC13A gene therapy

Summary

TDP-43 is a protein that plays an important role in the assembly line that converts information stored in our DNA into molecules called RNA, which are used as the template for making the proteins within our cells. TDP-43 is known to be dysregulated in about 97% of people living with MND. Dysregulated TDP-43 introduces mistakes into UNC13A RNA, resulting in the production of a faulty protein. The presence of the faulty UNC13A protein is associated with worse disease progression. 

In this project, Professor Fratta is designing and developing novel “antisense oligonucleotides” (ASOs) to target faulty UNC13A. ASOs are DNA-like molecules that silence faulty genetic material leaving the correct genetic material to function as normal within the cell.

Why this research is important

ASOs are a relatively new technology, which have already shown a lot of promise in MND (tofersen is an ASO targeting the SOD1 gene mutation in people living with SOD1-MND). This research will generate the pre-clinical data needed to take this treatment forward into human trials.

View our infographic to learn more about gene therapies and to find out more about TDP-43, check out our infographic or watch the short documentary below. 

This project has led to the launch of a spin-out company with significant investment to take this ASO forward to clinical trials.

*This project is part of the Motor Neuron Disease Translational Research Fund and is co-funded by LifeArc and MND Association. Total funding for this grant is £492,874.00.