Ancient viral DNA linked to MS and ALS

The study, conducted by researchers from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King's College London and Northwell Health, focused on human endogenous retroviruses (HERVs) – remnants of ancient retroviral infections that are now integral parts of our DNA. Using a cutting-edge genomic technique, the team identified specific HERV expression signatures associated with multiple sclerosis and amyotrophic lateral sclerosis (also known as motor neuron disease). These results suggest that viral elements in our DNA may play a role in the development of these neurodegenerative diseases.

Neurodegenerative diseases are characterized by progressive degeneration and loss of neurons, leading to a deterioration in the structure and function of the nervous system. Multiple sclerosis is one of the most common neurodegenerative diseases in young adults. More than 150,000 people in the UK suffer from the condition throughout their lives. Amyotrophic lateral sclerosis is rarer, with around 5,000 cases in the UK, and is associated with a worse prognosis.

Understanding the genetic architecture of neurodegenerative diseases

The study, published in Brain, Behavior, and Immunity, represents an important advance in understanding the complex genetic architecture of neurodegenerative diseases. While previous studies have suggested a link between HERVs and these diseases, this is one of the first to identify specific HERVs associated with associated with susceptibility to disease.

Researchers analyzed data from hundreds of brain samples to find the connection between HERV expression and genetic risk factors for four neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis and multiple sclerosis. They identified a robust HERV signature on chromosome 12q14 (MER61_12q14.2), which is associated with amyotrophic lateral sclerosis, and another on chromosome 1p36 (ERVLE_1p36.32a), which is associated with multiple sclerosis. These viral sequences appear to be involved in homophilic cell adhesion – a process essential for communication between cells in the brain. No robust signatures were observed for Alzheimer's and Parkinson's diseases, although the authors highlight that larger studies may reveal new connections in the future.

Implications for future treatments

As the global burden of neurodegenerative diseases continues to increase – over 50 million people are currently affected worldwide, a number that is predicted to nearly triple by 2050 – these findings provide a promising direction for future research and treatment development. This discovery opens new possibilities for therapeutic interventions against HERVs. By better understanding how these viral elements trigger disease, researchers hope it could help develop novel treatments that could mitigate the effects of neurodegenerative diseases.

The research was partly funded by the National Institute for Health and Care (NIHR) Maudsley Biomedical Research Centre, the National Institutes of Health (NIH) and the Psychiatry Research Trust.

“Ancient viral DNA in the human genome linked to neurodegenerative diseases” (Rodrigo Duarte, Douglas Nixon, Timothy Powell) was published in Brain, Behavior, and Immunity. DOI: 10.1016/j.bbi.2024.10.020.