mRNA and the Brain: A Groundbreaking Era for Brain Disease Treatment
- Valeria Yela
- Jul 22
- 8 min read
Written by: Valeria Yela
Edited by: Sherry Guo, Lyla Prasad
Illustrated by: Emily Baek
Introduction: The Rise of mRNA Technology
Messenger RNA (mRNA) technology is revolutionizing modern medicine, with its transformative potential highlighted by the rapid development of COVID-19 vaccines. mRNA is a type of genetic material produced from DNA that carries instructions for cells to make proteins [1]. While much of the early success of mRNA technology has focused on fighting infectious diseases, recent developments are expanding its applications into new areas. Its success has led to a growing interest in applying mRNA vaccine technology to neurological disorders such as multiple sclerosis (MS) and glioblastoma [2]. As research progresses, mRNA vaccine platforms for infectious diseases have shown promising results in both animal models and humans [3, 4].
How mRNA Vaccines Work Compared to Traditional Vaccines
mRNA vaccines have transformed immunology by introducing an effective approach for disease prevention and treatment [1]. Traditional vaccines train the immune system to recognize and fight pathogens by exposing the body to a weakened or inactive form of the pathogen, such as a bacterium, virus, parasite, or fungus [5]. This triggers an immune response, leading to the production of antibodies, which are protective proteins produced by the immune system that help fight off infections. If exposed to the pathogen later, the immune system responds quickly because the vaccine –– whether traditional or mRNA –– has already prompted it to produce antibodies that recognize and fight off the pathogen, preventing illness. Unlike conventional vaccines, however, mRNA vaccines do not contain the actual pathogen. Instead, they deliver genetic instructions (mRNA) that tell the body’s cells to temporarily produce a harmless protein fragment found on the surface of the pathogen [1]. This protein triggers the immune system to recognize it as foreign and produce antibodies in response. These antibodies remain in the body, allowing the immune system to recognize and fight the pathogen more effectively if exposed in the future [5].
mRNA Vaccines and Multiple Sclerosis (MS)
For instance, MS is a chronic autoimmune disease in which the immune system mistakenly attacks the myelin sheath, which are the protective covers that surround brain and spinal cord nerves. This damage disrupts nerve signals and communication between the brain and the rest of the body. Consequently, this affects muscles, vision, and eventually breathing. Over time, MS leads to permanent nerve damage. Some people may lose the ability to walk on their own or move at all, bringing enormous suffering to those with the disease [6]. In response to this, mRNA vaccines are being investigated for their potential to induce antigen-specific immune tolerance. This is a process that trains the immune system to ignore only the wrongly targeted molecules without weakening the body’s defenses [2]. This approach is different from traditional immune-suppressing treatments, which reduce immune activity throughout the body and increase the risk of infections. For instance, immunosuppressive drugs like methotrexate and azathioprine work by broadly dampening the immune system to reduce inflammation. In doing so, they also suppress the body’s ability to fight off infections, which can lead to serious side effects over time, such as liver toxicity, increased cancer risk, and overall immune dysfunction [7].
To be specific, traditional vaccines are unable to treat MS as they are designed to train the immune system to recognize and fight off external pathogens like viruses or bacteria. They are not made to correct the immune system when it mistakenly attacks the body’s own healthy cells. As of now, there is no cure for MS, but treatments can help reduce further damage. In contrast, mRNA vaccines spark a side of optimism as it provides hope for treatment and long-term management. They could potentially correct the immune system’s harmful behavior. A new study conducted by researchers from the College of Pharmacy at the University of Illinois Niazi et al (2023) explores the usage of an mRNA vaccine to treat MS. By introducing an mRNA that encodes specific autoantigens––which are proteins in the body mistakenly targeted by the immune system––these vaccines may help retrain the immune system to recognize them as self, therefore reducing the risk of autoimmune attacks [8]. So far, preclinical studies in mice conducted by a team of researchers from institutions including TRON Oncology at the University Medical Center of Johannes Gutenberg University, the University Medical Center Mainz, and BioNTech SE have demonstrated that these mRNA-based interventions can delay the onset of disease and reduce its severity. While this is not yet a cure, it marks a major step forward. With ongoing research and clinical testing, mRNA vaccines are emerging as a powerful tool not only for managing MS, but possibly for preventing or even reducing damage caused by immune system dysfunction.
mRNA Vaccines and Glioblastoma
Glioblastoma, on the other hand, is an aggressive brain tumor that can spread to the spinal cord and often proves to be fatal. It is the most common type of cancerous brain tumor. This cancer originates in glial cells responsible for supporting nerve cells located in the brain and spinal cord. It is characterized by its rapid growth and its tendency to destroy healthy surrounding tissue. It accounts for approximately 50% of all malignant brain tumors in the United States, with over 10,000 deaths annually [9]. The average survival time following diagnosis is between 12 to 28 months, even with conventional treatments such as surgery, radiation, and chemotherapy [10]. The five-year survival rate remains low, at approximately 5% to 7% [11]. Given its poor prognosis and resistance to conventional therapies, researchers are exploring mRNA vaccines as a novel approach to stimulate the immune system to target and eliminate glioblastoma tumor cells.
Conventional treatments such as surgery to remove the tumor, radiation therapy to target cancerous cells, and/or chemotherapy to slow or stop cell division have had limited long-term success in managing glioblastoma due to its highly invasive nature. However, mRNA vaccine technology targets this disease with the development of lipid nanoparticles, which are tiny carriers used to deliver drugs or genetic materials like mRNA into the body’s cells. A recent study conducted by Hamouda et al (2024) emphasizes how these vaccines would be designed to encode tumor-specific antigens, which would train the immune system to recognize and attack cancer cells [12]. Preclinical studies have demonstrated encouraging results in treating this disease. mRNA vaccines are highly effective at inducing both humoral and cellular immune responses. This means they activate different parts of the immune system, including antibody production, immune cells that directly attack cancer, and cytotoxic T-lymphocytes, a type of white blood cell capable of targeting and destroying cancer cells directly.
In another study conducted by Keskin et al (2019), early-phase clinical trials have been conducted to assess the efficacy and safety in utilizing mRNA vaccines on human patients with glioblastoma. In phase I, personalized mRNA vaccines were created to target patients’ neoantigens, which are unique proteins that appear on the surface of cancer cells and are not found on normal healthy cells [12]. By targeting neoantigens, the vaccines help the immune system to recognize cancer cells as foreign and attack them without harming the healthy tissue. As a result, the vaccines were well-tolerated, with no serious adverse reactions reported. Specifically, 8 out of 16 patients exhibited prolonged progression-free survival. This refers to the length of time during and after the treatment when a patient had the disease. However, for these patients, this disease did not worsen. In fact, survival extended beyond the expected median for glioblastoma, indicating a promising therapeutic benefit.
Challenges in mRNA Vaccine Delivery for Neurological Disorders
Nevertheless, significant challenges remain. One major obstacle is the difficulty of crossing the blood-brain barrier (BBB), a protective layer of cells that act as a filter blocking harmful or foreign pathogens from entering the brain while allowing essential ones through. Additionally, there are concerns about the long-term safety of mRNA vaccines before they can be used for neurological disorders. Rare neurological complications such as encephalitis and other inflammatory conditions have been reported in association with mRNA vaccination, though they are uncommon [14]. Delivering mRNA therapeutics safely across the BBB without triggering unintended immune responses remains a significant hurdle [15]. Furthermore, because mRNA vaccine technology is still relatively new, long-term data on their safety, especially regarding effects in the central nervous system, remain limited and are still being collected [15]. Although mRNA vaccines offer a promising therapeutic technology to target these challenging conditions, overcoming these barriers will be essential. Still, with ongoing research, could mRNA vaccine revolutionize brain disease treatment just like it did for COVID-19?
Emerging Solutions to Cross the Blood-Brain Barrier
In response, researchers are exploring various delivery systems to facilitate the transport of mRNA into the brain. Recently, researchers have been using lipid nanoparticles (LNPs) designed to encapsulate mRNA. LNPs are tiny particles of fat that can sneak protein-building instructions past the brain’s blood-filtering system, enabling new treatments to target neurological disorders [16, 17]. These LNP carrying mRNA are injected into the veins. Once in the bloodstream, LNPs can pass the BBB and deliver the mRNA needed to treat or prevent disease [18]. Moreover, scientists are also studying engineered viral vectors, which use modified viruses to deliver genetic material, and focused ultrasound to open the BBB using sound waves to allow therapeutic molecules to pass through with more ease [19].
Conclusion: A New Era in Neurological Treatment?
Despite the promise of these cutting-edge methods, researchers remain cautious. Some preclinical studies have raised concerns regarding inflammation and unintended immune response. As with any emerging therapy, understanding the risks alongside the benefits is crucial. Ongoing research and clinical trials will be the key to ensuring safety for patients. Additionally, advances in molecular engineering could continue to enhance the effectiveness of these vaccines by improving their stability and ability to cross barriers like the BBB. This rapid progress in this field sparks an exciting future for neurology and humanity. Are we on the verge of a new era in neurology where once-incurable brain diseases become treatable?
References
[1] Pfizer. (n.d.). Harnessing the potential of mRNA. https://www.pfizer.com/science/innovation/mrna-technology
[2] Krienke, C., Kolb, L., Diken, E., Streuber, M., Kirchhoff, S., Bukur, T., ... & Nimmerjahn, F. (2021). A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis. Science, 371(6525), 145–153. https://doi.org/10.1126/science.aay3638
[3] Sahin, U., Karikó, K., & Türeci, Ö. (2014). mRNA-based therapeutics—developing a new class of drugs. Nature Reviews Drug Discovery, 13, 759–780. https://doi.org/10.1038/nrd4278
[4] Pardi, N., Hogan, M. J., Porter, F. W., & Weissman, D. (2018). mRNA vaccines — a new era in vaccinology. Nature Reviews Drug Discovery, 17(4), 261–279. https://doi.org/10.1038/nrd.2017.243
[5] Centers for Disease Control and Prevention (CDC). (2024). COVID-19 vaccine basics. https://www.cdc.gov/covid/vaccines/how-they-work.html
[6] Mayo Clinic. (2024). Multiple sclerosis (MS). https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms-causes/syc-20350269
[7] American Academy of Allergy, Asthma & Immunology (AAAAI). (n.d.). Immunosuppressive medication for the treatment of autoimmune disease. https://www.aaaai.org/conditions-treatments/related-conditions/immunosuppressive
[8] Niazi, S. K., et al. (2023). College of Pharmacy, University of Illinois. Anti-Idiotypic mRNA Vaccine to Treat Autoimmune Disorders.
[9] Glioblastoma Foundation. (2024). Glioblastoma multiforme. https://glioblastomafoundation.org/news/glioblastoma-multiforme
[10] Cleveland Clinic. (2024). Glioblastoma (GBM). https://my.clevelandclinic.org/health/diseases/17032-glioblastoma
[11] GBM Research. (2024). What is the average glioblastoma survival rate?https://www.gbmresearch.org/blog/glioblastoma-survival-rate
[12] Hamouda, M., et al. (2024). Experimental mRNA Vaccine Hints at Potential Against Glioblastoma.https://www.cancer.gov/news-events/cancer-currents-blog/2024/glioblastoma-mrna-vaccine-layered-nanoparticle
[13] Keskin, D. B., Anandappa, A. J., Sun, J., Tirosh, I., Mathewson, N. D., Li, S., ... & Wu, C. J. (2019). Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature, 565(7738), 234–239. https://doi.org/10.1038/s41586-018-0792-9
[14] The BMJ. (2024). Covid-19: Two rare vaccine side effects detected in large global study. https://www.bmj.com/content/384/bmj.q488
[15] Nature. (2024). Blood-brain barrier challenges and limited long-term safety data. https://www.nature.com/articles/s41380-024-02627-0
[16] Mount Sinai. (2025). New lipid nanoparticle platform delivers mRNA to the brain. https://www.mountsinai.org/about/newsroom/2025/new-lipid-nanoparticle-platform-delivers-mrna-to-the-brain-through-the-blood-brain-barrier
[17] Springer. (2024). Lipid nanoparticles deliver mRNA to the BBB. https://link.springer.com/article/10.1007/s12274-024-6827-7
[18] NCBI. (2022). Focused ultrasound/microbubbles-assisted BBB opening enhances LNP-mediated mRNA delivery to brain. https://pubmed.ncbi.nlm.nih.gov/35640764/
[19] Nagasaki University. (2022). Ultrasound-guided delivery across the BBB.
Comments