Remnants of ancient viral DNA in the human genome are associated with two neurodegenerative conditions: multiple sclerosis and motor neurone disease.

This new study's findings could pave the way for novel therapeutic approaches for these two neurological conditions that currently have limited treatment. By identifying how ancient viral DNA sequences influence immune responses, scientists might develop more targeted therapies that address underlying disease mechanisms.

Dr Rodrigo Duarte from King's College London, co-lead author of the study, said: 'Our findings offer robust evidence that specific viral sequences within our genome contribute to the risk of neurodegenerative diseases. These sequences are not just static fossils derived from ancient viral infections – they must be actively influencing brain function in ways we are only beginning to understand.'

Multiple sclerosis (MS) is a chronic autoimmune disease where the immune system attacks the protective covering of nerve fibres in the brain and spinal cord, leading to inflammation and nerve damage. Motor neurone disease, also known as amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative disorder that affects motor neurons, leading to muscle weakness, paralysis, and eventually loss of voluntary movement control.

The study, led by researchers at King's College London and the Feinstein Institute for Medical Research in New York, and published in Brain, Behaviour, and Immunity, explored the presence of human endogenous retroviruses (HERVs) – ancient viral DNA sequences that integrated into the human genome throughout evolution.

The researchers used genetic data from large genome wide association studies on ALS, MS, Alzheimer's disease, and Parkinson's disease brain tissue to explore links between genetic variations and HERVs.

Using advanced statistical tools, they investigated how genetic variations affected gene expression in specific regions of the cerebral cortex – the outer layer of the brain. Through their methods, the researchers identified a specific HERV sequence that was robustly associated with MS, and one HERV sequence associated with ALS. These specific HERV sequences may be involved in homophilic cell adhesion, a process critical for communication between brain cells and which previous research has found to be linked to neurodegeneration. No strong associations of HERVs were found for Alzheimer's disease or Parkinson's disease in the study.

HERVs make up about eight percent of the human genome, and while most are dormant, previous research has found that some may still influence immune responses. In the future, the researchers plan to explore how HERV sequences could be targeted to modulate immune responses in neurodegenerative diseases, opening new avenues for targeted therapies.

Dr Timothy Powell from King's College London, co-lead author of the study, said: 'Using large genetic datasets and a new analysis pipeline, this study is well equipped at pinpointing which specific HERVs are important in increasing susceptibility for neurodegenerative diseases. We now need to better understand how these HERVS impact on brain function, and whether or not targeting HERVs could offer new therapeutic opportunities.'