A groundbreaking Australian study is using a novel ‘recall by genotype’ method to understand why the Epstein-Barr virus triggers multiple sclerosis in some, but not others, long before symptoms ever appear.
Multiple sclerosis (MS) is a relentless and enigmatic disease. It emerges when the body’s own immune system mistakenly attacks the protective sheath covering nerve fibers, disrupting the vital communication between the brain and the rest of the body. This neurological assault can lead to a wide range of debilitating symptoms, from fatigue and numbness to vision problems and mobility challenges. For the more than 33,000 Australians living with MS, the journey is often unpredictable, and its origins remain one of modern medicine’s most pressing puzzles.
For years, scientists have chased two primary suspects in the development of MS: an individual’s genetic makeup and a past infection with the Epstein-Barr virus (EBV). EBV is incredibly common, best known for causing glandular fever, and it infects up to 90% of the global population. While the link between EBV and MS is strong, it presents a frustrating paradox: if the virus is nearly ubiquitous, why do only a tiny fraction of those infected go on to develop multiple sclerosis? The answer, researchers believe, lies at the intersection of these two suspects—in the intricate dance between our DNA and our immune system’s response to this common virus.
Now, a pioneering study from the University of South Australia (UniSA) is set to untangle this complex relationship. In an Australian first for MS research, a team led by Dr. David Stacey is employing a powerful new technique to hunt for the earliest biological clues of the disease, aiming to identify individuals at high risk before they experience a single symptom.
The Viral Trigger and the Genetic Blueprint
The central hypothesis of the UniSA study is that genetics holds the key to why EBV can be a catalyst for MS. “For many years we’ve known that the Epstein-Barr virus is a likely precursor for MS,” explains Dr. Stacey. “But because the virus affects up to 90% of the population, it’s difficult to pin down why some people go on to develop MS while others don’t.”
The research team posits that the difference isn’t the virus itself, but how a person’s immune system, guided by their unique genetic blueprint, reacts to it. It’s this genetically-programmed immune response that may, in some individuals, set the stage for the autoimmune cascade that defines MS. “We believe the way a person’s immune system responds to the Epstein-Barr virus may be a key factor, and genetics can help us uncover that,” Dr. Stacey adds.
To test this theory, the researchers needed a way to peer into the biology of people who are genetically susceptible to MS but have not yet developed the disease. This requires a novel and highly targeted approach.
A New Detective Tool: ‘Recall by Genotype’
This is where the study, funded by an MS Australia Incubator Grant, breaks new ground. The team is using an innovative research design known as ‘recall by genotype’ (RbG). This method flips traditional research on its head. Instead of recruiting patients who already have a disease, RbG allows scientists to proactively identify individuals based on their genetic risk profile.
The process will begin by analyzing the DNA of more than 1,000 South Australian participants who do not have an MS diagnosis. From their genetic data, the researchers will calculate a personalized “MS genetic risk score” for each person. This score is determined by looking at naturally occurring genetic variants that are known to be strongly associated with the disease.
Once these scores are calculated, the team will “recall” a select group of participants for further, more detailed testing. This recalled cohort will include individuals with a very high genetic risk for MS and, for comparison, a group with a very low genetic risk. By focusing on these two distinct groups, researchers can search for subtle biological differences with much greater precision and reliability.
“By grouping people based on their genetic profile, we expect to find those with a high genetic risk for MS will also show biological differences – even if they don’t have the disease,” Dr. Stacey notes. These differences, or “biomarkers,” could be the earliest warning signs—the faint biological whispers that precede the full-blown disease. Finding these markers is the holy grail for early detection, as they could form the basis of future predictive screening tools.
The Ethical Frontier of Genetic Knowledge
This cutting-edge research doesn’t just push scientific boundaries; it also ventures into complex ethical territory. The ‘recall by genotype’ method, while powerful, raises profound questions about the responsibility of sharing genetic risk information with participants.
“If we identify people who are at risk of developing MS, we need to consider how – and whether – to share that information, particularly as this information may not yet be clinically actionable,” says Dr. Stacey. In other words, what is the ethical obligation when you can tell someone they have a heightened risk for a disease for which there is currently no preventative cure?
This is not a question the research team is taking lightly. A crucial component of the study involves exploring these ethical, legal, and social implications. The findings will help establish standard operating procedures and guide how future genetic studies in Australia approach the sensitive issue of communicating personal risk, ensuring that participants are supported and informed responsibly.
Paving the Way for a New Era in MS Care
This UniSA study, a collaboration that includes the Perron Institute and the University of Adelaide, represents a foundational step toward a future where MS can be predicted and perhaps even prevented. While it won’t produce a cure overnight, its impact could be transformative.
By identifying reliable early biomarkers, the research could lead to the development of simple diagnostic tools, like a blood test, that could assess a person’s risk for MS years before the disease takes hold. This would open the door to early intervention strategies, allowing for treatments to be administered at a stage when they are most effective, potentially delaying or even halting the progression of the disease.
Ultimately, this investigation is about decoding the very first steps in the long and complex journey of multiple sclerosis. By untangling the threads that connect our genes, a common virus, and our immune system, these researchers are not just seeking to understand MS—they are building the knowledge base required to one day stop it in its tracks.
