Is multiple sclerosis hiding in your DNA?

Virus, Multiple Sclerosis, DNA

What if the missing environmental factor in some of our deadliest neurological diseases were really written in our genome? Writing for Frontiers in Genetics, researchers from the University of Düsseldorf in Germany explain how viruses ended up in our DNA and the impact on unsolved diseases like multiple sclerosis (MS).

The enemy within

A whopping eight percent of our DNA comes from viruses. Specifically, ones called retroviruses – and they didn’t get this name because they’re old. These viruses reverse the normal process of reading DNA to merge themselves with host’s genome.

Retroviruses are indeed old. They began merging with our earliest, primordial ancestors millions of years ago. Over the millennia, most of their remnants in our DNA – known as human endogenous retroviruses (HERVs) – have been silenced by mutations.

Others have evolved to fend off rival viruses and formed the prototypical immune system, which protects us from infections today. HERVs, however, might be the missing link in major “unsolved” neurological diseases.

“HERVs have been implicated in the onset and progression of MS, amyotrophic lateral sclerosis (ALS) and schizophrenia,” says senior author Prof Patrick Küry. “Dormant HERVs can be reactivated by environmental factors such as inflammation, mutations, drugs or infection from other viruses.”

Role in MS

Strong evidence links HERVs to MS. As Küry explains: “MS is caused by direct autoimmune attacks on myelin – the fatty coating of nerve cells – in the brain and spinal cord. But we don’t yet understand how these attacks are triggered.” A variety of studies suggest that reactivation of HERV could be just such a trigger.

“Retroviruses were first associated with MS in 1989, but only decades later was it realised that these are in fact HERVs,” Küry writes. “Subsequently, it was shown that levels of HERV RNA [strands of DNA] and protein are increased in the brain and spinal cord fluid of people with MS, as well as in their brain tissue post-mortem.

“By linking this HERV reactivation to autoimmune attacks in MS, it was found that HERV proteins can trigger an immune response against myelin, which triggers MS-like disease in mouse models.”

Experimental proof in humans

Similar experiments have linked HERVs to more distinct disease processes like progressive loss of motor neurons in ALS, also known as Lou Gehrig’s disease. In schizophrenia, a complex neurodevelopmental disorder, the link to HERVs is more circumstantial.

“HERV proteins have been reported to increase expression of schizophrenia-linked genes in cultured human brain cells. However, studies on people with schizophrenia show inconsistent changes in HERV expression,” Küry reports.

Whether or not HERVs contribute to these and other unexplained neurological conditions requires further investigation. An important step will be to test the effects of HERV-neutralising antibodies in humans.

“In relapsing MS patients, a phase two-B clinical trial, which uses HERV protein-neutralising antibody Temelimab, has been conducted. We’re now waiting to see if the treatment showed beneficial effects on remyelination or attenuated neurodegeneration,” Küry concludes.

For more information, access the original article on the Frontiers in Genetics website here.

Leave a Reply

Your email address will not be published. Required fields are marked *