1. Introduction
1.1. Introduction to Multiple Sclerosis (MS)
Multiple sclerosis (MS) is an autoimmune disease in which the myelin that surrounds neuron axons is attacked by our own immune cells, resulting in demyelination in the central nervous system (CNS) (Lassmann 2018). This demyelination reduces or inhibits the flow of neurotransmitters and signals across neurons and leads to several physical symptoms in MS patients, such as fatigue, weakness, impact on vision, a feeling of brain fog, etc. Worldwide, the disease impacts approximately 1.8 million people but is more common in women than men with a 3:1 ratio (WHO 2023).
The huge impact of MS in terms of the number of sufferers and the severe impact the disease has on their day-to-day lives makes further study of MS to allow advancements in treatment key.
1.2. Impact of Breastfeeding
In this blog, we will examine the proposed theory that BRCA genes could play a role in the treatment of MS.
It has long been observed that symptoms or relapses in MS patients decrease while exclusively breastfeeding. The benefits of this can last for 6-9 months or until the infant is consuming solids (Collorone et al. 2023). It has also been observed that breastfeeding reduces the risk of breast cancer, even in individuals with BRCA1 mutations (Stordal 2022). It seems logical to question whether there are common factors between these diseases that are resulting in the improved outcomes observed from breastfeeding.
While BRCA genes have become synonymous with breast cancer, all people have BRCA genes, and this blog focuses on them as a potential mechanism to target for treatment of MS.
2. BRCA gene expression; factors that could play a role in MS
While BRCA genes have a bad reputation for their role in breast cancer, they are critical genes. They have vital roles in DNA repair and genomic stability and function as tumour suppressor genes when mutations have not occurred. Some of the factors influenced by BRCA genes include 53BP1 (p53-binding protein 1), RAD51 and oligodendrocyte ubiquitination regulation (Gorodetska et al. 2019). Each of these factors also plays a role in MS and so indicates that BRCA could be targeted as a mechanism of treatment in MS.
53BP1 is a factor in tumour suppression but is also implicated in suppression of autoimmune diseases such as MS, this has been observed in both mice and human studies (Fierabracci & Pellegrino, 2016). A study done by Achiron et al. (2012) demonstrated that p53 can be used to alter MS to a benign state through apoptosis of the immune cells which attack myelin.
The homologous recombination factor, RAD51, plays a crucial role in DNA repair and replication. Research by Bhattacharya et al. (2017), shows RAD51 being indicated in immune signalling and preventing the build-up of self-DNA in the cytosol and disruption to this can play a role in cancer risk. The build-up of cytosolic self-DNA is also implicated in several neurodegenerative diseases, including MS, through the excessive triggering of the cGAS-STING pathway. The cGAS-STING pathway is responsible for the neuroinflammation response that occurs when it detects excess DNA in the cytosol (Dhapola et al. 2025).
A complex of BRCA1 and BRCA2 known as BRCC3, regulates the ubiquitination of oligodendrocytes which provide the myelin required to insulate axons. The ability to produce more myelin is an important treatment option for MS patients. A study by Wang et al. (2019) suggests that the BRCC3 complex levels are decreased in MS patients which leads to an increase in Lys63-linked ubiquitination and disrupts the balance of myelin proteins produced by oligodendrocytes. This, in turn, could potentially impact the disease progression of MS patients.
Each of these factors together shows that BRCA could be a mechanism to be used to aid MS patients by improving disease progression.
Figure 1: Mechanisms for BRCA gene impact on p53, RAD51 and oligodendrocytes to potentially improve MS outcomes. Created in https://BioRender.com.
2.1. Ways to use BRCA gene expression for the benefit of MS patients
BRCA genes can regulate p53 through dephosphorylation. BRCA2 binds directly to RAD51 and recruits it to areas of DNA damage for repair. BRCA genes can act as E3 ubiquitin ligases which can regulate myelin production (Gorodetska et al. 2019). If, as indicated above, BRCA proteins could be used to reduce the action of the immune system, maintain cell homeostasis by preventing the build up of DNA in the cytosol and promote myelin production, then use of therapeutics which up or down regulate BRCA genes could have a significant impact of MS patients.
Currently, it is not clear exactly how expression of BRCA genes is impacted by breastfeeding. Interestingly, a study of mice by Mueller and Roskelley in 2002 indicated that BRCA1 expression was high during pregnancy and then slowly decreased during lactation. Following lactation, levels spiked before falling again. There has not been any concrete work on the expression of BRCA genes during breastfeeding to date so further investigation is required to determine if the expression levels during breastfeeding could indicate whether up or downregulation of BRCA genes could be most beneficial to MS patients.
By looking at treatments that can influence BRCA gene expression, studies could be done to determine if these could also impact MS outcomes. For example, studies have shown that curcumin, which has long been used as an antioxidant and to reduce inflammation, can increase the levels of BRCA1 protein in cells. BRCA1 protein levels can be lower in cases of sporadic breast cancer than normal. A study by Al-Yousef et al. in 2020 found that curcumin could be used to increase BRCA1 protein levels in curcumin treated cell lines and suggested it as a potential therapeutic for breast cancer. Other studies have examined the impact of curcumin on MS. Bernardo et al. in 2021 investigated the potentials of curcumin on demyelinating diseases such as MS. They found that it has potential for promoting myelin production and reducing inflammation in MS.
3. Conclusion
While further research is required to fully understand the links between BRCA genes and MS, there appears to be significant overlap between them which could indicate that an effective MS therapy such as use of curcumin may be found. Through the study of BRCA genes and the overlapping factors between its roles in cancer prevention and immune response regulation, new insights into MS could on the horizon.
4. References
Achiron, A., Feldman, A., Magalashvili, D., Dolev, M. and Gurevich, M. (2012) ‘Suppressed RNA-Polymerase 1 Pathway Is Associated with Benign Multiple Sclerosis’, PLoS ONE, 7(10): e46871, available: https://doi.org/10.1371/journal.pone.0046871
Al-Yousef, N., Shinwari, Z., Al-Shahrani, B., Al-Showimi, M. and Al-Moghrabi, N. (2020). ‘Curcumin induces re‑expression of BRCA1 and suppression of γ synuclein by modulating DNA promoter methylation in breast cancer cell lines’, Oncology reports, 43(3), 827–838. https://doi.org/10.3892/or.2020.7473
Bernardo, A., Plumitallo, C., De Nuccio, C., Visentin, S. and Minghetti, L. (2021) ‘Curcumin promotes oligodendrocyte differentiation and their protection against TNF-α through the activation of the nuclear receptor PPAR-γ’, Scientific Reports, 11, 4952, https://doi.org/10.1038/s41598-021-83938-y
Bhattacharya, S., Srinivasan, K., Abdisalaam, S., Su, F., Raj, P., Dozmorov, I., Mishra, R., Wakeland, E., Ghose, S., Mukherjee, S. and Asaithamby, A. (2017) ‘RAD51 interconnects between DNA replication, DNA repair and immunity’, Nucleic Acids Research, 45(8), 4590–4605, available: https://doi.org/10.1093/nar/gkx126
Collorone, S., Kodali, S. and Toosy, A. (2023) ‘The protective role of breastfeeding in multiple sclerosis: Latest evidence and practical considerations’, Frontiers in Neurobiology, 13, 1090133, available: https://doi.org/10.3389/fneur.2022.1090133
Dhapola, R., Paidlewar, M., Kumari, S., Sharma, P., Vellingiri, B., Medhi, B. and HariKrishnaReddy, D. (2025) ‘cGAS-STING and neurodegenerative diseases: A molecular crosstalk and therapeutic perspective’, International Immunopharmacology 159, 114902, available: https://doi.org/10.1016/j.intimp.2025.114902
Fierabracci, A. and Pellegrino, M. (2016) ‘The Double Role of p53 in Cancer and Autoimmunity and Its Potential as Therapeutic Target’, International Journal of Molecular Sciences, 17(12), 1975, available: https://doi.org/10.3390/ijms17121975
Gorodetska, I., Kozeretska, I. and Dubrovska, A. (2019) ‘BRCA Genes: The Role in Genome Stability, Cancer Stemness and Therapy Resistance’, Journal of Cancer, 10(9), 2109-2127, available: https://doi.org/10.7150/jca.30410.
Lassman, H. (2018) ‘Multiple Sclerosis Pathology’, Cold Spring Harb Perspective Medicine, 8(3), a028936, available: https://doi.org/10.1101/cshperspect.a028936
Mueller, C. and Roskelley, C. (2002) ‘Regulation of BRCA1 expression and its relationship to sporadic breast cancer’, Breast Cancer Research, 5(1), 45-52, available: https://doi.org/10.1186/bcr557
Stordal, B. (2022) ‘Breastfeeding reduces the risk of breast cancer: A call for action in high-income countries with low rates of breastfeeding’, Cancer Medicine, 12(4), 4616-4625, available: https://doi.org/10.1002/cam4.5288
Wang, C., Deneen, B. and Tzeng, S. (2019) ‘BRCA1/BRCA2-containing complex subunit 3 controls oligodendrocyte differentiation by dynamically regulating lysine 63-linked ubiquitination’, Glia, 67(9), 1775-1792, available: https://doi.org/10.1002/glia.23660
World Health Organization (2023) Multiple Sclerosis [Fact Sheet], available: https://www.who.int/news-room/fact-sheets/detail/multiple-sclerosis [accessed 24 Oct 2025].
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This was really interesting to see another take on how to treat women with ms and breastfeeding. I would love to know, at what stage of pregnancy would this be most effective? Would it be during or post partum?
Hi Emma,
Thank you for your question. Based on my research, I think this would likely be most effective postpartum as the risk of MS relapses increases after pregnancy but is also when breastfeeding provides protection (Langer-Gould et al. 2020). If BRCA pathways can support remyelination and lower immune activity, then trying to manipulate them shortly after delivery could potentially reinforce those benefits. Future studies could also explore whether starting during the third trimester, when relapse rates are most reduced (Wyszynski, 2025), helps promote recovery before birth, but this would need to be thoroughly examined to avoid any potential risks to the baby in utero.
References
Langer-Gould, A., Smith, J., Albers, K., Xiang, A., Wu, J., Kerezsi, E., McClearnen, K., Gonzales, E., Leimpeter, A., & Van Den Eeden, S. (2020). ‘Pregnancy-related relapses and breastfeeding in a contemporary multiple sclerosis cohort’, Neurology, 94(18), e1939–e1949, available: https://doi.org/10.1212/WNL.0000000000009374
Wyszynski, D. (2025) ‘Pregnancy and Multiple Sclerosis: A Narrative Review of Clinical Outcomes, Disease Activity, and Treatment Considerations’, Multiple Sclerosis and Related Disorders, 102, 106643, available: https://doi.org/10.1016/j.msard.2025.106643Get rights and content
I really learned a lot from this post! It always intriges me to learn about how seemingly separate systems can intertwine in the human body. You mentioned that there is no solid evidence to support whether increased or decreased BRCA gene expression is more beneficial to MS treatment, and that curcumin is a potential treatment that increases BRCA1. Is there a drug that could show potential for promoting myelination in the case that downregulation of BRCA genes proves more beneficial?