Pregnancy - The Trojan Horse for Autoimmune Solutions
By delving into women's unique physiological experiences, such as pregnancy, we can unlock secrets of the human body that have far-reaching implications for both sexes. Just as scientists were shocked to discover new antibiotics and cancer treatments on the depths of the ocean floor, studying women’s health offers a similar treasure trove of biological mysteries that may have applications outside of female health.
Pregnancy Modifies the Immune System
Pregnancy represents a unique immunological state that provides a compelling subject for scientific inquiry, particularly in understanding how the human body accepts foreign genetic material without a typical immune rejection. The fetus, which carries genetic material from both parents, including foreign antigens from the father, is not recognized and attacked as an outsider by the mother's immune system. This remarkable tolerance is largely due to specific adaptations within the maternal immune system, which shifts towards increased tolerance during pregnancy.
A key element in this adaptation involves T cells, which are crucial for maintaining a healthy pregnancy. These cells, which normally function to protect the body against pathogens and cancerous cells, are modulated during pregnancy to prevent them from attacking the fetus.1 This modulation involves a delicate balance, protecting the body against infections while avoiding an aggressive response to the fetus.
Over the years, the scientific literature has underscored that these immunological adaptations are not indicative of a weakened immune system but rather a reprogrammed one that fosters cooperation between the maternal and fetal immune systems. In other words, pregnancy does not suppress the immune system; it reprograms it.
Imagine harnessing that switch. Being able to turn off autoimmune attacks at will, like flipping a light switch. That’s precisely what pregnancy does for diseases like Multiple Sclerosis (MS), and we’re only beginning to understand how to bottle that effect into a treatment.
Why Multiple Sclerosis (MS) is better during pregnancy
One of the most fascinating phenomena observed in the realm of autoimmune diseases is the significant improvement in symptoms of MS during pregnancy. This temporary relief has intrigued researchers and clinicians alike, leading to pivotal (and very recent!) studies that aim to understand the underlying mechanisms.
MS is a chronic and often debilitating autoimmune disorder that predominantly affects the central nervous system, which includes the brain, spinal cord, and optic nerves. Characterized by the immune system's aberrant attack on myelin, the fatty substance that encases and protects nerve fibers, MS disrupts the flow of information within the brain and between the brain and the body. This disruption manifests as a range of symptoms that can vary widely in severity, from mild issues such as numbness in the limbs to severe disabilities like loss of vision or mobility.
There is a remarkable decrease in MS relapses in pregnant people with MS. The third trimester can decrease by up to 70 percent.2 This reduction is not isolated to MS but is also seen in other autoimmune conditions like rheumatoid arthritis.3 Initial studies, including the groundbreaking Pregnancy in Multiple Sclerosis (PRIMS) study, have consistently shown that the rate of MS relapses diminishes throughout pregnancy, only to increase again a few months postpartum.4
To delve deeper into the immunological changes during pregnancy that could influence this phenomenon, researchers have focused on the behavior of T cells, which play a crucial role in MS pathology. Significant epigenetic changes, particularly DNA methylation in T cells, were observed in a detailed study led by Sandra Hellberg, an assistant professor at the Department of Biomedical and Clinical Sciences at Linköping University.5 These changes, which help regulate how genes are turned on and off, appear to align closely with the amelioration of MS symptoms observed during the latter stages of pregnancy.
Further, the study highlighted the interaction of gene networks during pregnancy, linking them directly to key processes in the immune system that correlate with disease improvement. The most significant changes in T cell behavior and gene expression were documented in the last third of pregnancy, coinciding with the greatest reduction in MS relapse frequency. These adaptations appear to be reversed after childbirth, correlating with a recurrence of MS symptoms.
These insights are crucial as they not only enhance our understanding of MS during pregnancy but also open potential pathways for therapeutic interventions that mimic the immunological state of pregnancy. This could lead to innovative treatments that offer new hope for managing MS and other similar autoimmune diseases more effectively.
Did We Mention Autoimmune Conditions are Big Business?
The autoimmune disease sector represents a significant and growing area of opportunity within the pharmaceutical industry. The financial stakes are considerable, with the autoimmune disease diagnostics market valued at nearly $2 billion and the treatment market at approximately $72.3 billion in 2023.6,7 This burgeoning interest is underscored by robust investment activity, with over $1.7 billion poured into companies developing treatments for autoimmune disorders in the first half of 2024 alone.8
Investment bank Oppenheimer's data highlights that the field of immunology, which encompasses autoimmune conditions, is outpacing many other areas in healthcare investment, trailing only oncology.9 This surge in investment is driven by the substantial commercial success of immunology drugs, which are increasingly becoming top revenue generators within the pharmaceutical industry. For instance, AbbVie's Humira, the best-selling drug of all time, has generated about $200 billion in sales over two decades, treating various inflammatory conditions. Following Humira's patent expiration in 2023, AbbVie has successfully shifted focus to other immunology drugs like Skyrizi and Rinvoq, bringing in $3.1 billion in the first quarter of 2024.
The appeal of immunology drugs lies not only in their financial returns but also in their high success rates in clinical trials. Enhanced scientific understanding has made it easier for drugmakers to develop effective treatments. Furthermore, the multifaceted utility of these drugs across various conditions offers a safety net in clinical development; even if a drug fails in one indication, it can still succeed in another, maximizing investment returns.
Market research firm Fortune Business Insights projects that the global immunology market will grow to $257 billion by 2032, a stark increase from $98 billion in 2023.10 This projected growth reflects not only the current demand but also the potential for future expansion as the immune system's role in diseases, including those not traditionally considered immune-based, like Alzheimer’s, becomes more apparent.
Moreover, the prevalence of autoimmune diseases is increasing. Some estimates suggest that as much as 12% of the population in the US annually, pointing to a growing patient base and a pressing need for innovative solutions.11 Given these dynamics, it is clear why immunology remains a lucrative and attractive field for investors like Blackstone Life Sciences, which continues to target this area for long-term strategic investments like $250 million for a new autoimmune disease CAR-T cell therapy company.
But what if the next billion-dollar breakthrough in immunology did not come from where investors expected? It could be hidden in plain sight within women’s health. The scientific signals are clear: pregnancy research could hold the key to unlocking the next wave of autoimmune treatments. Therefore, directing resources toward studying pregnancy promises to advance our understanding of human biology and aligns with smart investment strategies in the high-stakes arena of healthcare innovation. This approach is not just scientifically prudent; it is a financially astute strategy that taps into a burgeoning market with immense potential for returns and societal impact.
Conclusion - Women’s Health as a Trojan Horse to Healthcare Homeruns
The realm of pregnancy represents a largely untapped area of scientific exploration with immense potential to revolutionize our understanding of human health. Much like the unknown mysteries of the ocean floor that hold the secrets to novel antibiotics and potential cures for diseases, the study of pregnancy could unlock similar groundbreaking discoveries across various medical fields.
The smartest investors don’t follow the herd, they see opportunities where others overlook them. Pregnancy research is the Trojan Horse of healthcare: an unassuming entry point into one of the fastest-growing, most lucrative markets in biotech. Those who recognize its potential now will be at the forefront of a paradigm shift in immunology, reaping massive returns while others play catch-up.
About the Author: Dr. Brittany Barreto is a global key opinion leader in women's health innovation and best-selling author of Unlocking Women’s Health, FemTech and the Quest for Gender Equity. She is a Molecular Geneticist by training with experience founding and investing in startups. She is the founder of FemHealth Insights boutique consulting firm and host of the FemTech Focus podcast.
Citations
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Voskuhl R, Momtazee C. Pregnancy: Effect on Multiple Sclerosis, Treatment Considerations, and Breastfeeding. Neurotherapeutics. 2017 Oct;14(4):974-984. doi: 10.1007/s13311-017-0562-7. PMID: 28766273; PMCID: PMC5722767.
Jethwa H, Lam S, Smith C, et al. Does rheumatoid arthritis really improve during pregnancy? A systematic review and metaanalysis. J Rheumatol 2019;46:245–50. doi:10.3899/jrheum.180226
Vukusic S, Hutchinson M, Hours M, Moreau T, Cortinovis-Tourniaire P, Adeleine P, Confavreux C; Pregnancy In Multiple Sclerosis Group. Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse. Brain. 2004 Jun;127(Pt 6):1353-60. doi: 10.1093/brain/awh152.
Zenere A, Hellberg S, Papapavlou Lingehed G, Svenvik M, Mellergård J, Dahle C, Vrethem M, Raffetseder J, Khademi M, Olsson T, Blomberg M, Jenmalm MC, Altafini C, Gustafsson M, Ernerudh J. Prominent epigenetic and transcriptomic changes in CD4+ and CD8+ T cells during and after pregnancy in women with multiple sclerosis and controls. J Neuroinflammation. 2023 Apr 27;20(1):98. doi: 10.1186/s12974-023-02781-2.
Business Wire. (2024). Autoimmune Disease Diagnostics Market Report 2024.
GlobeNewswire. (2024). Global Autoimmune Disease Therapeutics Market to Reach USD 116.81 Billion by 2032, Growing at a 5.52% CAGR.
DeAngelis, A. (October 14 2024). Chasing CAR-T, biotech finds its next gold rush in autoimmune disease. STAT News.
Margolis, M. Oppenheimer. (Jan 2024). Oppenheimer Life Sciences Year-End 2023 Review.
Mikulic, M. (May 22 2024) Pharmaceutical market: worldwide revenue 2001-2023. Pharmaceutical Products and Reports. Statista
Miller FW. The increasing prevalence of autoimmunity and autoimmune diseases: an urgent call to action for improved understanding, diagnosis, treatment, and prevention. Curr Opin Immunol. 2023 Feb;80:102266. doi: 10.1016/j.coi.2022.102266. Epub 2022 Nov 26. PMID: 36446151; PMCID: PMC9918670.