Novel Therapeutic Strategies for Prion Diseases
Research Article
Open Access
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Novel Therapeutic Strategies for Prion Diseases

Ivy Shi 1*
1 Acton-Boxborough Regional High School
*Corresponding author: ccb9b9@gmail.com
Published on 24 September 2025
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TNS Vol.137
ISSN (Print): 2753-8826
ISSN (Online): 2753-8818
ISBN (Print): 978-1-80590-371-0
ISBN (Online): 978-1-80590-372-7
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Abstract

Prion diseases are a group of rare but invariably fatal neurodegenerative disorders caused by the misfolding of the normal cellular prion protein (PrPC) into its pathogenic isoform (PrPSc). The unique infectious nature of PrPSc, its ability to self-propagate, and the severe neuropathological changes it induces, including neuronal loss, spongiform degeneration, and gliosis, make these disorders particularly challenging to treat. Currently, there are no approved disease-modifying therapies, and clinical management remains entirely supportive. However, advances in molecular biology and translational neuroscience have led to promising therapeutic strategies. Antisense oligonucleotides have demonstrated efficacy in reducing PrP expression and slowing disease progression in preclinical models, while immunotherapy offers both preventive and therapeutic potential through antibody- or vaccine-based approaches. Small-molecule inhibitors, including compounds that disrupt prion aggregation or stabilize PrPC, also remain an area of active exploration. Despite these advances, major challenges persist: the inability of many therapeutic agents to cross the blood-brain barrier, prion strain variability that limits treatment generalizability, and the difficulty of diagnosing disease before significant neurodegeneration occurs. Future therapeutic success will depend on early detection, improved drug delivery systems, and combination therapies that simultaneously target multiple aspects of prion pathogenesis. Together, these developments highlight both the promise and the complexity of translating experimental prion therapeutics into viable clinical applications.

Keywords:

Prion disease, therapeutics, Prp

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Shi,I. (2025). Novel Therapeutic Strategies for Prion Diseases. Theoretical and Natural Science,137,58-65.

References

[1]. Liu, F., Lu, W., & Liu, L. (2024). New implications for prion diseases therapy and  prophylaxis. Frontiers. https: //www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2024.1324702/full

[2]. Shim, K. H., Sharma, N., & An, S. S. A. (2022). Prion therapeutics: Lessons from the past.  PMC. https: //pmc.ncbi.nlm.nih.gov/articles/PMC9754114/

[3]. Raymond, G. J., Zhao, H. T., Race, B., Raymond, L. D., Williams, K., Swayze, E. E.,   Graffam, S., Le, J., Caron, T., Stathopoulos, J., O’Keefe, R., Lubke, L. L., Reidenbach,   A. G., Kraus, A., Schreiber, S. L., Mazur, C., Cabin, D. E., Carroll, J. B., Minikel, E. V., Kordasiewicz, H., & Caughey, B. (2019). Antisense oligonucleotides extend survival of prion-infected mice. PMC. https: //pmc.ncbi.nlm.nih.gov/articles/PMC6777807/

[4]. Cantara, S., SImoncelli, G., & Ricci, C. (2024). Antisense Oligonucleotides (ASOs) in Motor  Neuron Diseases: A Road to Cure in Light and Shade. PMC.  https: //pmc.ncbi.nlm.nih.gov/articles/PMC11083842/

[5]. Minikel, E. V., Zhao, H. T., Le, J., O’Moore, J., Pitstick, R., Graffam, S., Carlson, G. A.,   Kavanaugh, M. P., Kriz, J., Kim, J. B., Ma, J., Wille, H., Aiken, J., McKenzie, D., Doh-ura,   K., Beck, M., O’Keefe, R., Stathopoulos, J., Caron, T., … Vallabh, S. M.. (2020). Prion  protein lowering is a disease-modifying therapy across prion disease stages, strains and  endpoints. Oxford Academic. https: //academic.oup.com/nar/article/48/19/10615/5878830

[6]. Tremblay, P., Meiner, Z., Galou, M., Heinrich, C., Petromilli, C., Lisse, T., Cayetano, J.,   Torchia, M., Mobley, W., Bujard, H., DeArmond, S. J., & Prusiner, S. B. (1998).  Doxycycline control of prion protein transgene expression modulates prion disease in  mice. PMC. https: //pmc.ncbi.nlm.nih.gov/articles/PMC22873/

[7]. Teruya, K., & Doh-ura, K. (2017). Insights from Therapeutic Studies for PrP Prion Disease.  PMC. https: //pmc.ncbi.nlm.nih.gov/articles/PMC5334251/

[8]. Forloni, G. (2025). Doxycycline: An essential tool for Alzheimer’s disease. PMC.  https: //pmc.ncbi.nlm.nih.gov/articles/PMC12165865/

[9]. Fede, G. D., Giaccone, G., Salmona, M., & Tagliavini, F. (2018). Translational Research in  Alzheimer’s and Prion Diseases. PMC. https: //pmc.ncbi.nlm.nih.gov/articles/PMC5869996/

[10]. Ma, Y., & Ma, J. (2020) Immunotherapy against Prion Disease. PMC.  https: //pmc.ncbi.nlm.nih.gov/articles/PMC7157205/

[11]. Napper, S., & Schatzl, H. M. (2023). Vaccines for prion diseases: a realistic goal?. PMC.  https: //pmc.ncbi.nlm.nih.gov/articles/PMC9918406/

[12]. Burchell, J. T., & Panegyres, P. K. (2016). Prion diseases: immunotargets and therapy.  PMC. https: //pmc.ncbi.nlm.nih.gov/articles/PMC4970640/

[13]. Kong, Q. (2006). RNAi: a novel strategy for the treatment of prion diseases. PMC.  https: //pmc.ncbi.nlm.nih.gov/articles/PMC1679715/

[14]. White, M. D., Farmer, M., Mirabile, I., Brandner, S., Collinge, J., & Mallucci, G. R. (2008).  Single treatment with RNAi against prion protein rescues early neuronal dysfunction and  prolongs survival in mice with prion disease. PMC. https: //pmc.ncbi.nlm.nih.gov/articles/PMC2474561/

[15]. Pfeifer, A., Eigenbrod, S., Al-Khadra, S., Hofmann, A., Mitteregger, G., Moser, M., Bertsch,   U., & Kretzschmar, H. (2006). Lentivector-mediated RNAi efficiently suppresses prion  protein and prolongs survival of scrapie-infected mice. JCI. https: //www.jci.org/articles/view/29236

[16]. Golding, M. C., Long, C. R., Carmell, M. A., Hannon, G. J., & Westhusin, M. E. (2006).  Suppression of prion protein in livestock by RNA interference. PNAS.  https: //www.pnas.org/doi/full/10.1073/pnas.0600813103

References

[1]. Liu, F., Lu, W., & Liu, L. (2024). New implications for prion diseases therapy and  prophylaxis. Frontiers. https: //www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2024.1324702/full

[2]. Shim, K. H., Sharma, N., & An, S. S. A. (2022). Prion therapeutics: Lessons from the past.  PMC. https: //pmc.ncbi.nlm.nih.gov/articles/PMC9754114/

[3]. Raymond, G. J., Zhao, H. T., Race, B., Raymond, L. D., Williams, K., Swayze, E. E.,   Graffam, S., Le, J., Caron, T., Stathopoulos, J., O’Keefe, R., Lubke, L. L., Reidenbach,   A. G., Kraus, A., Schreiber, S. L., Mazur, C., Cabin, D. E., Carroll, J. B., Minikel, E. V., Kordasiewicz, H., & Caughey, B. (2019). Antisense oligonucleotides extend survival of prion-infected mice. PMC. https: //pmc.ncbi.nlm.nih.gov/articles/PMC6777807/

[4]. Cantara, S., SImoncelli, G., & Ricci, C. (2024). Antisense Oligonucleotides (ASOs) in Motor  Neuron Diseases: A Road to Cure in Light and Shade. PMC.  https: //pmc.ncbi.nlm.nih.gov/articles/PMC11083842/

[5]. Minikel, E. V., Zhao, H. T., Le, J., O’Moore, J., Pitstick, R., Graffam, S., Carlson, G. A.,   Kavanaugh, M. P., Kriz, J., Kim, J. B., Ma, J., Wille, H., Aiken, J., McKenzie, D., Doh-ura,   K., Beck, M., O’Keefe, R., Stathopoulos, J., Caron, T., … Vallabh, S. M.. (2020). Prion  protein lowering is a disease-modifying therapy across prion disease stages, strains and  endpoints. Oxford Academic. https: //academic.oup.com/nar/article/48/19/10615/5878830

[6]. Tremblay, P., Meiner, Z., Galou, M., Heinrich, C., Petromilli, C., Lisse, T., Cayetano, J.,   Torchia, M., Mobley, W., Bujard, H., DeArmond, S. J., & Prusiner, S. B. (1998).  Doxycycline control of prion protein transgene expression modulates prion disease in  mice. PMC. https: //pmc.ncbi.nlm.nih.gov/articles/PMC22873/

[7]. Teruya, K., & Doh-ura, K. (2017). Insights from Therapeutic Studies for PrP Prion Disease.  PMC. https: //pmc.ncbi.nlm.nih.gov/articles/PMC5334251/

[8]. Forloni, G. (2025). Doxycycline: An essential tool for Alzheimer’s disease. PMC.  https: //pmc.ncbi.nlm.nih.gov/articles/PMC12165865/

[9]. Fede, G. D., Giaccone, G., Salmona, M., & Tagliavini, F. (2018). Translational Research in  Alzheimer’s and Prion Diseases. PMC. https: //pmc.ncbi.nlm.nih.gov/articles/PMC5869996/

[10]. Ma, Y., & Ma, J. (2020) Immunotherapy against Prion Disease. PMC.  https: //pmc.ncbi.nlm.nih.gov/articles/PMC7157205/

[11]. Napper, S., & Schatzl, H. M. (2023). Vaccines for prion diseases: a realistic goal?. PMC.  https: //pmc.ncbi.nlm.nih.gov/articles/PMC9918406/

[12]. Burchell, J. T., & Panegyres, P. K. (2016). Prion diseases: immunotargets and therapy.  PMC. https: //pmc.ncbi.nlm.nih.gov/articles/PMC4970640/

[13]. Kong, Q. (2006). RNAi: a novel strategy for the treatment of prion diseases. PMC.  https: //pmc.ncbi.nlm.nih.gov/articles/PMC1679715/

[14]. White, M. D., Farmer, M., Mirabile, I., Brandner, S., Collinge, J., & Mallucci, G. R. (2008).  Single treatment with RNAi against prion protein rescues early neuronal dysfunction and  prolongs survival in mice with prion disease. PMC. https: //pmc.ncbi.nlm.nih.gov/articles/PMC2474561/

[15]. Pfeifer, A., Eigenbrod, S., Al-Khadra, S., Hofmann, A., Mitteregger, G., Moser, M., Bertsch,   U., & Kretzschmar, H. (2006). Lentivector-mediated RNAi efficiently suppresses prion  protein and prolongs survival of scrapie-infected mice. JCI. https: //www.jci.org/articles/view/29236

[16]. Golding, M. C., Long, C. R., Carmell, M. A., Hannon, G. J., & Westhusin, M. E. (2006).  Suppression of prion protein in livestock by RNA interference. PNAS.  https: //www.pnas.org/doi/full/10.1073/pnas.0600813103

Cite this article

Shi,I. (2025). Novel Therapeutic Strategies for Prion Diseases. Theoretical and Natural Science,137,58-65.

Data availability

The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.

About volume

Volume title: Proceedings of ICBioMed 2025 Symposium: AI for Healthcare: Advanced Medical Data Analytics and Smart Rehabilitation

ISBN: 978-1-80590-371-0(Print) / 978-1-80590-372-7(Online)
Editor: Alan Wang
Conference website: https://2025.icbiomed.org/auckland.html
Conference date: 17 October 2025
Series: Theoretical and Natural Science
Volume number: Vol.137
ISSN: 2753-8818(Print) / 2753-8826(Online)

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