Code of Multiple Sclerosis: How Blood Proteins Could Unlock New Treatments

Multiple sclerosis (MS) remains one of the most challenging neurodegenerative diseases to treat. This chronic, immune-driven condition damages the protective myelin sheath around nerves, disrupting communication between the brain and body. While treatments exist, they are far from perfect—many patients still experience relapses, progressive disability, and treatment side effects.

A study published in Experimental Gerontology (Liu et al., 2024) takes an exciting step forward by combining cutting-edge genetics and proteomics to uncover new therapeutic targets for MS. The research team integrated large-scale genetic data with blood protein profiles, pinpointing key proteins that may drive MS risk—and that could one day be targeted with drugs.

Why Genetics Alone Isn’t Enough
Over the past decade, genome-wide association studies (GWAS) have revealed hundreds of genetic variants linked to MS. The catch? Most of these variants lie in non-coding regions of DNA, meaning they influence how genes are regulated rather than directly coding for disease-causing proteins. This makes it difficult to translate genetic signals into druggable targets.

That’s where proteome-wide association studies (PWAS) come in. Instead of stopping at DNA, PWAS links genetic variants to protein abundance in the blood. Since proteins are the workhorses of the cell—and the main targets of most drugs—this approach provides a more direct line between genetics, biology, and therapy.

The Study in a Nutshell
The researchers combined two massive datasets:

MS genetic data: from over 115,000 people (47,429 MS patients and 68,374 controls).

Blood proteomics data: from 7,213 participants, measuring thousands of proteins using advanced assays.

Using statistical tools, they asked: Which proteins show genetically predicted differences in abundance that are linked to MS risk?

Key Findings
25 candidate proteins emerged as associated with MS risk.

7 proteins showed strong evidence of a causal role in MS:

Protective: Tenascin XB (TNXB) and CD59 (higher levels = lower MS risk).

Risk-promoting: Pleckstrin (PLEK), Caspase-3 (CASP3), Complement receptor 1 (CR1), TAPBPL, and Ataxin-3 (ATXN3).

3 proteins—PLEK, CR1, and CD59—were validated as highly likely to share causal genetic variants with MS.

CR1 stood out as particularly promising, because it is already targeted by the drug Eculizumab, approved for other immune-related conditions.

What Do These Proteins Do?
PLEK (Pleckstrin): A signaling protein in immune cells. It amplifies inflammation, potentially fueling the overactive immune response in MS.

CR1 (Complement receptor 1): A key regulator of the complement system, which helps clear pathogens but can also attack the body’s own cells if unbalanced. Its dysregulation has been linked to autoimmune conditions.

CD59: A natural “brake” on the complement system, preventing excessive immune attacks on healthy cells. Higher CD59 levels appear to shield against MS damage.

This paints a fascinating picture: MS risk may hinge on the delicate balance of immune-activating versus immune-protecting proteins in the bloodstream.

Why This Matters for MS Treatment
Today’s MS drugs mostly work by broadly suppressing the immune system. While effective, this comes with risks—patients can become more vulnerable to infections and cancer.

The beauty of proteomic insights is precision. Instead of shutting down the whole immune system, new drugs could fine-tune specific proteins like CR1 or PLEK. This opens the door to treatments that are both more effective and safer.

Even more exciting: drugs like Eculizumab, which already act on complement pathways, could be repurposed for MS, speeding up the path from discovery to patient benefit.

Looking Ahead
Of course, challenges remain. This study focused on European populations, so findings need to be confirmed across diverse groups. Also, while blood proteins are easier to study and target, MS primarily affects the brain—future work should connect these blood signals with what’s happening in the central nervous system.

Still, the results are a leap forward. By uniting genetics with proteomics, researchers are moving closer to the holy grail of personalized MS treatment—one that targets the right proteins, in the right patients, at the right time.

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:
Liu, Y., Wang, Q., Zhao, Y., Liu, L., Hu, J., Qiao, Y., ... & Qin, C. (2024). Identification of novel drug targets for multiple sclerosis by integrating plasma genetics and proteomes. Experimental Gerontology, 194, 112505.