Evidence growing for the role of angiogenesis in MND

What has the new research found?

The researchers, based in Ireland, UK, USA and Sweden, found seven new Angiogenin mutations. These were found in 15 people with MND, four of whom had the rare, familial form of MND that affects approximately 5-10% of all cases of the disease. Eleven mutations were found in people with the apparently ‘sporadic’ form of the disease. DNA samples from over 1,600 people with MND were analysed in this research. No Angiogenin mutations were found in the 1,200 samples analysed from people who were not affected by the condition. This is the first time that Angiogenin mutations have been found in families affected by familial MND.

What does this research mean for people with MND now?

This research will lead to a greater understanding of motor neurone disease. As these mutations are found in such a small proportion of people with MND, their current clinical significance is likely to be small. No routine tests for these Angiogenin mutations are available.

What does angiogenin do?

Angiogenin is involved in a biological process called angiogenesis that makes new blood vessels in the body. VEGF a gene that has already been implicated in MND, also regulates angiogenesis. Thus there is a possible rationale for the involvement of angiogenin in MND.

Gene defects – ‘mutations’ or ‘variations’?

The difference between a genetic ‘variation’ and a ‘mutation’ is their likely effect (known as their ‘penetrance’) and their frequency in the population. Some gene defects have a large effect – where one copy of the defect will cause disease in that person (gene mutation). At the other extreme, other defects may be present in approximately half the population (gene variation). These variations may act in combination with other genetic, lifestyle and environmental factors and contribute to the risk of developing disease.

How have the researchers described this work?

As Dr Orla Hardiman mentions in the Royal College of Surgeons in Ireland press release "What we have identified opens up a whole new avenue of enquiry and points in a new direction for future research". Dr Matthew Greenway, added that "MND has many causes. Angiogenin mutations are certainly part of the story, but there are many other genes that might also be important. The challenge is to identify these and to understand the way in which these genes interact to cause the disease. Understanding this process will then allow us to find new pathways for treatment."

How does this research build on earlier work?

Dr Greenway and colleagues had already identified a role for Angiogenin in motor neurone disease in earlier research, where variations in Angiogenin were more common in people with MND in the Irish, Scottish and American population. In the study published in Nature Genetics, Dr Greenway and colleagues re-analysed the same DNA samples in more detail, and found seven further gene defects (mutations) that are likely to have a bigger impact (higher penetrance) on the chances of someone developing the disease.