Precision in Practice: Personalised Medicine and the Female Face of Multiple Sclerosis

A girl on ice: tracing shadows to multiple sclerosis

In the biting cold of a Dutch winter in 1385, the frozen canals of Schiedam sparkled beneath a pale sun in the Netherlands. Children laughed and skated, slicing smooth arcs and circles across the glassy surface. Amongst them was Lidwina, a bright and active 15-year-old, known in her town for her gentle aura and strong health. But fate intervened. During what should have been a regular afternoon, Lidwina fell violently on ice, striking her side. At first, it seemed like a bad bruise, perhaps a cracked rib. But, unlike other falls, Lidwina’s pain didn’t fade. It lingered and persisted, deepening into a strange weakness that would come to haunt her body for the rest of her life, something that no one saw coming. In the weeks that followed, Lidwina’s mobility worsened. She struggled to stand, her legs felt incredibly heavy, and her balance faltered. Local healers and saintmen, guided by the beliefs of that time, prescribed herbs and fasting. They whispered of penance and sainthood, but her symptoms grew more and more unusual.

What began as intense pain in her limbs grew  into sensations of burning and stabbing, her muscles spasming, and over time  losing the ability to walk completely, leaving her paralyzed. As the years passed, the little girl suffered from open sores and infections, possibly due to being bedridden for years. But, was that all? tThe pathology also led to her vision being dimmed, sometimes even going dark in one eye - a possible sign of optic neuritis, one of what now is known to be a hallmark of multiple sclerosis (MS). Over the next 38 years, Lidwina’s condition confined her to bed, where she endured chronic pain, involuntary movements, and progressive disability. Yet, retained her sense of faith and often spoke of her suffering as a spiritual trial.

"Women are 2-3x more likely to be diagnosed with MS than men, a gap that has widened over the past few decades"

A retrospective diagnosis?

To some people, even centuries later, Ludiwina’s story would be referred back to, detailed in hagiographies and church records, representing the first whisper of a disease that today affects millions. Whilst neurologists and clinical practitioners trace back Lidwina’s case to be the earliest recorded features of MS, to date, her story reminds us that medical discovery doesn’t begin in the lab - it begins with people. Very often, women’s symptoms were long overlooked, misinterpreted or spiritualized highlighting a need for talking about gender based differences in health and disease. What, thus, becomes even more important, is to realize that beneath the spiritual interpretations of the past lies a complex neurological condition, rooted in immune dysfunction, inflammation, and the delicate architecture of the central nervous system.

Body’s own defences become its most insidious threat

Traditionally defined as a chronic, immune-mediated neurodegenerative disease of the central nervous system (CNS), MS is characterized by inflammation, demyelination, axonal loss and gliosis. Pathological hallmarks of MS are formation of lesions in the white and grey matter, most commonly found in the periventricular areas, optic nerves, brainstem, cerebellum, and spinal cord. However, at its very core, MS is an autoimmune disease that begins in the peripheral immune system, where a combination of genetic susceptibility — most notably HLA-DRB1*15:01 — and environmental triggers like Epstein-Barr Virus  and vitamin D deficiency activate naïve T cells. These auto-reactive T cells then express molecules such as VLA-4 and chemokine receptors that allow them to cross the blood-brain barrier into the CNS. Following this event, T cells release pro-inflammatory cytokines (IFN-γ, IL-17, TNF-α), which recruit monocytes, B cells, and microglia, amplifying inflammation and leading to myelin degradation and oligodendrocyte damage. B cells further drive MS by presenting antigens and producing oligoclonal bands — IgG antibodies found in the cerebrospinal fluid. In progressive MS, they may form lymphoid-like follicles in the meninges, contributing to cortical demyelination. Thereby, the body’s immune system that is meant to protect becomes the very force that destroys: a silent saboteur.

Lesions, layers and progression: molecular mapping of MS

At the heart of MS are lesions - distinct and discrete areas of damage scattered throughout the CNS, each telling a different part of the disease's evolving narrative. But, do lesions in MS present in a similar way? Well, they differ in their cellular makeup, molecular activity, location and stage of progression. Whilst some are active, teeming with inflammatory cells and demyelinating activity, others are chronic active, featuring a slow-burning rim of immune activity surrounding a core of damage. Additionally, there are inactive lesions where the battle has ended, leaving scar tissue behind, and demyelinating lesions, where some healing and repair may be underway. Considering this scenario, understanding the diversity and dynamics of these lesions is essential — not only for understanding disease severity and progression, but also for developing biomarkers that can guide diagnosis, monitor disease activity, and inform therapeutic decisions. This particularly becomes crucial in progressive MS, where lesion activity often becomes more diffuse and neurodegeneration may outpace inflammation.

MS Atlas: A molecular map of lesion stages

A recent landmark study by Frisch et al. provides an invaluable tool for decoding the complexity of MS. Using high throughput screening and transcriptomic profiling of post-mortem brain tissue from patients with progressive MS, the study mapped differential gene expression (DEG) signatures across five distinct lesion types: active, inactive, chronic active, remyelinating, and normal-appearing white matter. This resulted in an publicly accessible molecular atlas  allowing researchers to visualize the shifting cellular and molecular landscape at each lesion stage. Breakthrough findings of this MS molecular atlas included:

1. Examining distinct DEG profiles that exist for each lesion type, supporting the idea that MS pathology is highly stage-specific.

2. Chronic active lesions (common in progressive MS) show a sustained expression of pro-inflammatory genes, implicating ongoing, smoldering immune activity.

3. Remyelinating lesions exhibited upregulation of genes involved in oligodendrocyte function and repair, offering clues for regeneration-focused therapies.

Overall, this study identified potential biomarkers and pathway-level differences that may guide future drug development and precision-targeted interventions. Importantly and interestingly, this atlas doesn’t just catalog damage, but opportunities! With tools like this, researchers and clinicians are better equipped to stratify patients, predict disease course, and tailor treatments based on the molecular fingerprint of their lesions.

Molecules to populations: who gets MS and why does it matter?

While the cellular and molecular hallmarks of MS reveal the disease’s inner workings, the bigger picture lies in whom MS affects, and how. Well, MS does not strike at random. It follows distinct demographic patterns, and at the forefront of these is a striking gender disparity. Globally, women are two to three times more likely to be diagnosed with MS than men, a gap that has widened over the past few decades. This isn’t just an epidemiological curiosity, but a call to reframe how we understand the disease, how we diagnose it, and most importantly, how we treat it. The reasons to look into gender disparity in MS and why women are more susceptible to it are multifaceted: to begin with, hormonal factors play a key role. Estrogen and progesterone, which fluctuate throughout life events like menstruation, pregnancy, and menopause, significantly influence immune responses. For instance, MS relapse rates drop dramatically during the third trimester of pregnancy, when estrogen levels are high, only to rebound postpartum. Genetics also intersect with sex. Women are more likely to carry the HLA-DRB1*15:01 allele, the strongest known genetic risk factor for MS. Additionally, X-linked immune regulatory genes may drive heightened immune reactivity in women. Lastly, immunological differences reveal that women tend to mount more robust, but also more dysregulated immune responses — explaining their increased risk for a range of autoimmune conditions, including MS. While women are more likely to develop MS, their experience of the disease often differs from men and not always in ways that benefit them, highlighting a crucial need for early intervention, disease-modifying therapies (DMTs) and personalized medicine.

"(...) the future of MS care isn’t just personalized — it’s inclusive, intentional, and driven by those who have been overlooked for too long"

Precision in pink: personalized MS care for women

Though MS disproportionately affects women, the research and treatment landscape has only recently begun to reflect that reality. Fortunately, we are now entering an era where personalized medicine is no longer theoretical — it’s tangible, and evolving! A range of DMTs, including interferons, glatiramer acetate, fingolimod, ocrelizumab, and natalizumab, are already in clinical use and can be tailored based on disease activity, patient age, comorbidities, and their reproductive plans. Some treatments, like glatiramer acetate and interferon-beta, are considered safer options during pregnancy, offering flexibility for women who are planning families. Others are designed for high-efficacy early intervention and are being studied in the context of long-term immune reprogramming. In the current light, even though true sex-informed personalization remains a work in progress, tools like MRI lesion profiling, neurofilament light chain  biomarkers, and genetic screening for HLA-DRB1*15:01 help clinicians stratify risk and monitor disease progression. Meanwhile, digital health platforms and patient-centered data collection are enabling more responsive, individualized treatment plans.

In terms of aging women, very few therapies are rigorously tested across hormonal life stages. Women entering menopause, for instance, may experience changes in disease course, yet there is minimal guidance on how treatments should be adapted. Clinical trials often underrepresent women, and even fewer account for factors like hormonal contraception or menstrual cycling in therapeutic outcomes. This is precisely why we need targeted investment, policy, and research that centers women—not as a subgroup, but as a biological priority.

MS awareness week: Advocacy through strength and equity

As we mark MS awareness week, we are reminded that advocacy isn’t just about raising visibility, it’s about pushing for equity. Women have always been at the forefront of MS, as patients, caregivers, researchers, and even as advocates. Yet, they’ve often received care built on data that doesn't fully reflect them, and it's time to change that. This week, let’s create awareness and voice our opinions  for action: for clinical trials that reflect the diversity of the MS population, for therapies that adapt to the hormonal and life-stage needs of women, for biomarkers and monitoring tools that make truly personalized care the norm, not the exception. Because, the future of MS care isn’t just personalized — it’s inclusive, intentional, and driven by those who have been overlooked for too long. And that future? It’s already in motion.

References

(1)   Orrell RW. Multiple Sclerosis: The History of a Disease. J R Soc Med. 2005 Jun;98(6):289. PMCID: PMC1142241

(2)   Lassmann H. Multiple Sclerosis Pathology. Cold Spring Harb Perspect Med. 2018 Mar 1;8(3):a028936. doi: 10.1101/cshperspect.a028936. PMID: 29358320; PMCID: PMC5830904.

(3)   Frisch T, Elkjaer ML, Reynolds R, Michel TM, Kacprowski T, Burton M, Kruse TA, Thomassen M, Baumbach J, Illes Z. Multiple Sclerosis Atlas: A Molecular Map of Brain Lesion Stages in Progressive Multiple Sclerosis. Netw Syst Med. 2020 Aug 27;3(1):122-129. doi: 10.1089/nsm.2020.0006. PMID: 32954379; PMCID: PMC7500075.

(4)   Derfuss T. Personalized medicine in multiple sclerosis: hope or reality? BMC Med. 2012 Oct 4;10:116. doi: 10.1186/1741-7015-10-116. PMID: 23035757; PMCID: PMC3523020.

(5)   Hauser SL, Cree BAC. Treatment of Multiple Sclerosis: A Review. Am J Med. 2020 Dec;133(12):1380-1390.e2. doi: 10.1016/j.amjmed.2020.05.049. Epub 2020 Jul 17. PMID: 32682869; PMCID: PMC7704606

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This article was written by Sirjan Chhatwal and edited by Julia Dabrowska, with graphics produced by Suzana Sultan and Sirjan Chhatwal. If you enjoyed this article, be the first to be notified about new posts by signing up to become a WiNUK member (top right of this page)! Interested in writing for WiNUK yourself? Contact us through the blog page and the editors will be in touch.