Long-Term Clinical Outcomes of Hematopoietic Stem Cell Transplantation in Multiple Sclerosis

To determine whether autologous hematopoietic stem cell transplantation is able to induce durable disease remission in people with multiple sclerosis (MS), scientists analyzed the long-term outcomes after transplant in a large cohort of MS patients.
[Neurology]
Boffa, G., Massacesi, L., Inglese, M., Mariottini, A., Capobianco, M., Lucia, M., Amato, M. P., Cottone, S., Gualandi, F., Gobbi, M. D., Greco, R., Scimè, R., Frau, J., Zimatore, G. B., Bertolotto, A., Comi, G., Uccelli, A., Signori, A., Angelucci, E., … Mancardi, G. (2021). Long-Term Clinical Outcomes of Hematopoietic Stem Cell Transplantation in Multiple Sclerosis. Neurology. https://doi.org/10.1212/WNL.0000000000011461 Cite
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Designed PKC-Targeting Bryostatin Analogs Modulate Innate Immunity and Neuroinflammation

Scientists showed that multiple synthetically accessible bryologs replicate the anti-inflammatory effects of bryostatin-1 on innate immune cells in vitro, and a lead bryolog attenuates neuroinflammation in vivo.
[Cell Chemical Biology]
Abramson, E., Hardman, C., Shimizu, A. J., Hwang, S., Hester, L. D., Snyder, S. H., Wender, P. A., Kim, P. M., & Kornberg, M. D. (2021). Designed PKC-targeting bryostatin analogs modulate innate immunity and neuroinflammation. Cell Chemical Biology, 0(0). https://doi.org/10.1016/j.chembiol.2020.12.015 Cite
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Role of miRNAs Shuttled by Mesenchymal Stem Cell-Derived Small Extracellular Vesicles in Modulating Neuroinflammation

Scientists identified nine miRNAs significantly dysregulated in IFN-γ-primed MSCs, but present at different levels in their derived small extracellular vesicles.
[Scientific Reports]
Giunti, D., Marini, C., Parodi, B., Usai, C., Milanese, M., Bonanno, G., Kerlero de Rosbo, N., & Uccelli, A. (2021). Role of miRNAs shuttled by mesenchymal stem cell-derived small extracellular vesicles in modulating neuroinflammation. Scientific Reports, 11(1), 1740. https://doi.org/10.1038/s41598-021-81039-4 Cite
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Role of miRNAs Shuttled by Mesenchymal Stem Cell-Derived Small Extracellular Vesicles in Modulating Neuroinflammation

Investigators showed that miR-467f and miR-466q modulate the pro-inflammatory phenotype of activated N9 microglia cells and of primary microglia acutely isolated from late symptomatic SOD1G93A mice, a murine ALS model, by downregulating Tnf and Il1b expression.
[Scientific Reports]
Giunti, D., Marini, C., Parodi, B., Usai, C., Milanese, M., Bonanno, G., Kerlero de Rosbo, N., & Uccelli, A. (2021). Role of miRNAs shuttled by mesenchymal stem cell-derived small extracellular vesicles in modulating neuroinflammation. Scientific Reports, 11(1), 1740. https://doi.org/10.1038/s41598-021-81039-4 Cite
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The TGF-β Superfamily Cytokine Activin-A Is Induced during Autoimmune Neuroinflammation and drives Pathogenic Th17 Cell Differentiation

Scientists examined the T cell-intrinsic role of Activin-A, a TGF-β superfamily member closely related to TGF-β1, in pathogenic Th17 cell differentiation. Activin-A expression was increased in individuals with relapsing-remitting multiple sclerosis and in mice with experimental autoimmune encephalomyelitis.
[Immunity]
Wu, B., Zhang, S., Guo, Z., Bi, Y., Zhou, M., Li, P., Seyedsadr, M., Xu, X., Li, J., Markovic-Plese, S., & Wan, Y. Y. (2021). The TGF-β superfamily cytokine Activin-A is induced during autoimmune neuroinflammation and drives pathogenic Th17 cell differentiation. Immunity, 0(0). https://doi.org/10.1016/j.immuni.2020.12.010 Cite
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A Noninflammatory mRNA Vaccine for Treatment of Experimental Autoimmune Encephalomyelitis

Scientists showed that systemic delivery of nanoparticle-formulated 1 methylpseudouridine-modified messenger RNA coding for disease-related autoantigens results in antigen presentation on splenic CD11c+ antigen-presenting cells in the absence of costimulatory signals.
[Science]
Krienke, C., Kolb, L., Diken, E., Streuber, M., Kirchhoff, S., Bukur, T., Akilli-Öztürk, Ö., Kranz, L. M., Berger, H., Petschenka, J., Diken, M., Kreiter, S., Yogev, N., Waisman, A., Karikó, K., Türeci, Ö., & Sahin, U. (2021). A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis. Science, 371(6525), 145–153. https://doi.org/10.1126/science.aay3638 Cite
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Inducing Immune Tolerance with Dendritic Cell-Targeting Nanomedicines

Scientists review the challenges and opportunities in using nanoparticles as a delivery mechanism to target dendritic cells and induce immunomodulation, emphasizing their versatility.
[Nature Nanotechnology]
Inducing immune tolerance with dendritic cell-targeting nanomedicines | Nature Nanotechnology. (n.d.). Retrieved January 5, 2021, from https://www.nature.com/articles/s41565-020-00810-2 Cite
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Microglia Facilitate Repair of Demyelinated Lesions via Post-Squalene Sterol Synthesis

By integrating gene expression profiling, genetics and comprehensive phenotyping, the authors found that, paradoxically, sterol synthesis in myelin-phagocytosing microglia/macrophages determined the repair of acutely demyelinated lesions.
[Nature Neuroscience]
Berghoff, S. A., Spieth, L., Sun, T., Hosang, L., Schlaphoff, L., Depp, C., Düking, T., Winchenbach, J., Neuber, J., Ewers, D., Scholz, P., van der Meer, F., Cantuti-Castelvetri, L., Sasmita, A. O., Meschkat, M., Ruhwedel, T., Möbius, W., Sankowski, R., Prinz, M., … Saher, G. (2020). Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis. Nature Neuroscience, 1–14. https://doi.org/10.1038/s41593-020-00757-6 Cite
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B Cell Depletion Therapies in Autoimmune Disease: Advances and Mechanistic Insights

The authors update our understanding of B cell biology, review the results of clinical trials using B cell depletion therapies (BCDT) in autoimmune indications, discuss hypotheses for the mechanism of action of BCDT and speculate on evolving strategies for targeting B cells beyond depletion.
[Nature Reviews Drug Discovery]
Lee, D. S. W., Rojas, O. L., & Gommerman, J. L. (2020). B cell depletion therapies in autoimmune disease: advances and mechanistic insights. Nature Reviews Drug Discovery, 1–21. https://doi.org/10.1038/s41573-020-00092-2 Cite
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FDA Approves Genentech’s Ocrevus® (ocrelizumab) Shorter Two-Hour Infusion for Relapsing and Primary Progressive Multiple Sclerosis

Genentech, Inc. announced that the US FDA has approved a shorter two-hour infusion time for Ocrevus®, dosed twice-yearly for those living with relapsing or primary progressive multiple sclerosis who have not experienced any prior serious infusion reactions.
[Genentech, Inc.]
Press Release
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Identification of Regulatory T Cell Molecules Associated with Severity of Multiple Sclerosis

Scientists determined whether the expression of functionally relevant TGF-β-regulated molecules was altered in Tregs from patients with multiple sclerosis.
[Multiple Sclerosis Journal]
Identification of regulatory T cell molecules associated with severity of multiple sclerosis - MA Tapia-Maltos, I Treviño-Frenk, HB García-González, M Rosetti, V Barriga-Maldonado, F Morales-Ramírez, DC López-Hernández, F Rosetti, JC Crispín, 2020. (n.d.). Retrieved December 15, 2020, from https://journals.sagepub.com/doi/abs/10.1177/1352458520977045 Cite
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