Location of retroviruses on a person’s DNA could be a factor in MND risk

As their MND Scotland research project comes to an end, we ask Professor Al Chalabi and Dr Iacoangeli from King’s College London about their project and what it has achieved.

Motor neuron disease (MND) is a neurodegenerative disease which targets the motor neurons, causing muscles to weaken over time. A cure has not yet been found, but research is ongoing.  We don’t know what triggers may lead to the onset of MND, but research suggests that a difference in genetics makes someone more or less likely to trigger disease development. Research into the genetic differences associated with MND is ongoing and aims to find possible causes and potential treatment targets. 

In 2018, MND Scotland provided £198,000 to Professor Al-Chalabi, Dr Iacoangeli and their research teams at King’s College London to investigate Human Endogenous Retroviruses (HERVs) and their potential in disease risk in MND.  The study aimed to compare the large amount of data available about genes involved in MND and use this to combine DNA, RNA, and clinical information to understand the role of HERVs in MND. This funding came to an end in 2024 – here we look at what it achieved. 

What is a HERV?

Human Endogenous Retroviruses are ancient viruses that have become a large part of our genome (around 8% of a person’s DNA). Most of them are inactive, but one of these, HERV, has the potential to produce viral particles. Known as HERV-K, this retrovirus has been linked to an increased risk of triggering diseases like cancer and neurodegeneration. When activated, HERV-K can be toxic to motor neurons, and people with MND frequently show HERV-K activation.  

What was done in this study?

The researchers looked at over 10,000 genomes, two-thirds of which were from people who had MND, and they examined:  

• The expression of HERV-Ks and where they lie on the genome, meaning where on our DNA HERV-K is located.  
• How environmental factors affect HERV-K genes 
• How differences in HERV-K gene expression affected the clinical presentation of MND.

They did this by using powerful computer methods that allowed them to screen, compare, and analyse genomic data and observe any patterns or similarities in people who had MND compared to people who didn’t have MND.  

What were the results?

The researchers managed to identify specific regions in the genome where HERV-Ks placement may contribute to MND disease risk. These areas of the genome were activated more in the motor cortex and cerebellum of people with MND.  

They also concluded that variations in HERV-K location between people with MND may indicate clinical qualities, such as earlier onset and differences in disease duration and progression. 

Additionally, there was no indication in this study that environmental factors could affect HERV-K activation.  

What’s next?

This study is just one piece of the puzzle, and as research builds our understanding of MND, over time we can see potential avenues for meaningful drug targets.  

These findings will be used in future research. Continuing from this study, the researchers hope to design experiments to understand the mechanism behind HERV-K . To build on the investment by MND Scotland in this area, Dr Iacoangeli, Prof Al-Chalabi and their labs have received 2 grants from the MRC and Rosetrees Trust amounting to approximately £1 million to further this research over the next 3-4 years. 

MND Scotland is proud to have sponsored the important research done by Professor Al-Chalabi, Dr Iacoangeli and their research teams. MND Scotland values funding promising research at any stage, unlocking stepping stones that will lead towards larger projects and clinical trials that impact the MND treatment landscape.