Can Your Genes Predict How Well MS Treatments Work?

Multiple sclerosis (MS) is a chronic autoimmune disease that damages the central nervous system, affecting around 2.5 million people worldwide. While we’ve made great strides in understanding the disease and developing treatments, one big challenge remains: predicting which therapy will work best for each patient.

A study published in the Annals of Clinical & Laboratory Science investigates this very question—looking at whether certain genetic differences in detoxification enzymes might influence how patients respond to natalizumab, a widely used treatment for MS.

Oxidative Stress and MS: A Key Connection
MS involves both inflammation and neurodegeneration. During flare-ups, immune cells flood into the central nervous system, releasing reactive oxygen species (ROS)—essentially “free radicals” that damage neurons, disrupt energy production, and trigger cell death.

Normally, our bodies have enzymes that neutralize these harmful molecules. Two of these detoxification enzymes, NQO1 and GSTP1, are especially important. However, some people carry genetic variants (polymorphisms) that reduce or completely eliminate the activity of these enzymes.

NQO1 (C609T variant): Some individuals completely lack NQO1 activity if they inherit two copies of the mutant allele.

GSTP1 (A313G variant): Certain variants reduce the enzyme’s ability to neutralize toxic compounds.

Given their role in oxidative stress, these genetic differences could shape how MS develops and how patients respond to treatment.

Natalizumab: More Than an Immunotherapy?
Natalizumab (marketed as Tysabri) is a monoclonal antibody that blocks immune cells from crossing the blood–brain barrier and attacking the nervous system. It is best known for treating relapsing-remitting MS (RRMS), but has also shown benefits in progressive forms of the disease.

Interestingly, some evidence suggests natalizumab might also reduce oxidative damage—a potential “bonus effect” beyond its immune-suppressing action. That raises an intriguing question: do patients with stronger natural antioxidant defenses respond better to natalizumab?

The Study: Genetics Meets Treatment Response Researchers in Athens followed 130 MS patients (58 men, 72 women) who were treated with natalizumab for an average of nearly 4 years. They analyzed patients’ DNA to determine whether they carried the NQO1 and GSTP1 polymorphisms, and compared genetic profiles with treatment outcomes.

Key Findings:
Most patients benefited: 88.5% responded positively to natalizumab, while 11.5% worsened.

Single mutations not decisive: Having one polymorphism (in either NQO1 or GSTP1) didn’t strongly predict treatment outcome.

Double mutations mattered: Patients carrying both polymorphisms were significantly more likely to be non-responders (46.7% vs. 23.1% in responders).

In other words, a double hit to antioxidant defenses appeared to weaken the benefits of natalizumab.

Why Does This Matter?
This study suggests that a patient’s genetic capacity to manage oxidative stress could influence how well they respond to natalizumab. While the findings don’t prove causation, they point to oxidative stress reduction as a possible mechanism behind the drug’s protective effects.

If confirmed by larger, multi-center studies, these insights could:

Guide personalized treatment: Genetic testing might one day help clinicians predict which MS patients will benefit most from natalizumab.

Support antioxidant-based strategies: Combining therapies that reduce oxidative stress could potentially boost outcomes.

Refine our understanding of MS: Highlighting the interplay between immune suppression and oxidative damage.

Final Thoughts
MS treatment is moving steadily toward personalized medicine, where therapies are tailored to a patient’s unique biology. This study adds a fascinating piece to that puzzle, linking detoxification gene variants to natalizumab response.

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:
Alexoudi, A., Zachaki, S., Stavropoulou, C., Gavrili, S., Spiliopoulou, C., Papadodima, S., ... & Sambani, C. (2016). Possible implication of GSTP1 and NQO1 polymorphisms on natalizumab response in multiple sclerosis. Annals of Clinical & Laboratory Science, 46(6), 586-591.