Developing AAV-GRN gene therapy for Motor Neuron Disease

To understand some of the mechanisms that are altered in the brain and spinal cord in MND and determine if there are any of a specific group of proteins (called GRNs) that protect from motor neurone death.

1475younbok Lee

PhD Student: TBC

Principal Investigator: Dr Younbok Lee

Lead Institution: King's College London

MND Association Funding: £104,744

Funding dates: October 2022 - September 2025

About the project

To cure motor neuron disease, it is essential to first understand which neural mechanisms are altered in the brain or spinal cord. Progranulin (PGRN) is glycoprotein secreted by cells in the brain which plays a key role in the lysosome (breaks down cells and removes waste). Defects in lysosomes could lead to the build-up of pathogenic TDP-43 seen in many cases of MND. The aim of this project is to characterise the role of each of the 8 GRNs (which make up PGRN) and identify which GRNs are protective against lysosomal defects and neuronal death. Any protective GRNs will then be used in a type of gene therapy and tested as a therapeutic strategy in animal models of  MND.

What does this mean for people living with MND?

In order to find potential new drugs to help treat MND, researchers need to understand the mechanisms and pathways that go wrong. This project aims to understand the role of GRN proteins and see if any have protective features against motor neurone death. If this is the case then this information can be used to help develop new therapeutic therapies.

Resources 

Want to find out more about this project and researchers? Check out the resources below:

News:

Gene therapy: £2m boost for… | UK DRI: UK Dementia Research Institute

Project code: 903-792