Identifying genes that modify SOD1 ALS in the mouse

Description:

What this research means to you: Mistakes (mutations) in the SOD1 gene cause around 20% of cases of the rare, inherited form of MND. Within families affected by SOD1 MND, the onset and progression of the disease can vary widely from one affected family member to another. This may be due in part to other genetic factors that can protect against or exacerbate the disease. This PhD studentship project will use the SOD1 mouse model of MND to look for these “disease modifying” genes. The findings may offer a valuable insight into the disease process and could indicate potential therapies.

The researcher explains in more detail: No single gene, including SOD1, acts alone. Genes and their protein products work within pathways and networks. This means that the effect of one gene, such as SOD1, can be modified by other genes and proteins within the same pathway or network. This has important implications for understanding the disease process. If we can find the genes in the SOD1 network, the ‘modifier’ genes, then this will give us a better understanding of how mutated SOD1 causes damage and also more information about how to target therapies.

Using genetic techniques to find ‘modifier’ genes has been routine in genetic investigations of fruit flies. It is now becoming an important technique in genetic investigations of mice such as the SOD1G93A animals, which are an important model of MND. This project aims to identify at least one modifier gene that affects motor neuron disease arising in SOD1G93A mice. Such a gene will inform us about SOD1 disease processes and possibly provide us with information of direct relevance to ALS therapy.

The Institute of Neurology Web Page