How One Gene and a Common Virus Might Predict Your MS Course
For anyone who has experienced a first demyelinating event (FDE)—a terrifying, sudden neurological episode that might be the start of multiple sclerosis—the biggest question is "What happens next?"
That question comes with a terrifying amount of uncertainty. Doctors have long struggled to predict who will go on to develop clinically definite MS, or how severe their disease will be. We know there are no clear genetic markers that can predict this progression... until, perhaps, now.
A 2017 study from Brain and Behavior, "Variation within MBP gene predicts disease course in multiple sclerosis", offers a fascinating new clue. It suggests that a specific gene, in combination with a common virus, might help us do exactly that.
The "Usual Suspect" with a Twist
The gene at the center of this story is MBP, which stands for Myelin Basic Protein.
This protein is exactly what it sounds like: a major, fundamental component of the myelin sheath, the protective coating around our nerve cells. In MS, the immune system mistakenly attacks this myelin, causing inflammation and damage.
Logically, you'd think the MBP gene would be a prime suspect for MS. But here's the twist: large-scale genetic studies (called GWAS) have never found a link between variations in the MBP gene and the risk of getting MS in the first place.
The researchers behind this study, led by Yuan Zhou, had a different idea. What if MBP isn't about onset, but about progression? They hypothesized that variations in this gene might determine the clinical course of MS after it has already begun.
What the Study Found: The "Aha!" Moment
To test this, the team studied 127 people who had recently experienced their first demyelinating event. They followed them for five years, tracking three key outcomes:
Whether they converted to clinically definite MS.
How many relapses they had.
Their change in disability, measured by the Expanded Disability Status Scale (EDSS).
They then looked at the participants' DNA, focusing on variations in the MBP gene.
One specific variant, rs12959006, stood out.
The results were striking. People carrying the "risk genotype" (CT or TT) for this one variant had significantly worse clinical outcomes.
More Relapses: They had a 1.74 times higher hazard of relapse compared to those with the CC genotype.
Faster Disability Progression: They showed a significantly greater rate of disability progression each year.
To put that disability finding in human terms: the researchers calculated that over five years, a person with the risk genotype would have an EDSS score 0.9 points higher than someone without it. In a disease where every point on the disability scale matters, that is a substantial difference.
Interestingly, the other seven MBP gene variants they tested showed no association at all.
The Plot Twist: It's Not Just the Gene
Here's where the story gets even more interesting. The researchers knew that MS isn't just about genes; it's a complex interplay between genes and the environment.
A well-known environmental factor linked to MS is prior infection with certain viruses, particularly Human Herpesvirus-6 (HHV-6).
The researchers looked for an interaction, and they found a powerful one.
For people without the risk gene (the CC genotype), their level of HHV-6 antibodies didn't seem to affect their disease course.
But for people with the risk gene (the CT+TT genotype), having high levels of HHV-6 antibodies was like pouring gasoline on a fire.
This "perfect storm" combination—the risk gene plus high HHV-6 antibodies—was associated with a 3.00 times higher hazard of relapse and a shocking 6.95 times higher hazard of converting to clinically definite MS.
Why This Matters for the Future
This study provides a "novel insight" into how MS progresses. It's one of the first to find a genetic marker not for getting MS, but for how the disease behaves.
It strongly supports the idea that MS is driven by complex gene-environment interactions. Here, a genetic variant seems to make a person's system more vulnerable to the effects of a past viral infection, leading to a worse disease course.
If these findings are replicated in larger studies, they could be a game-changer. This information could one day help "in developing prognostic algorithms". Imagine a future where, after a first demyelinating event, a doctor could run a simple genetic and serological test. This could help predict a patient's likely disease course and allow for a more personalized, aggressive, or measured treatment plan right from the very beginning.
Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.
References:
Zhou, Y., Simpson Jr, S., Charlesworth, J. C., Van Der Mei, I., Lucas, R. M., Ponsonby, A. L., ... & Taylor, B. V. (2017). Variation within MBP gene predicts disease course in multiple sclerosis. Brain and behavior, 7(4), e00670.
