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Updated: Dec 12, 2025

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In MS: Immunosuppression is passé.

Staley A Brod1

  • 1Department of Neurology, Medical College of Wisconsin, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI 53226, USA.

Multiple Sclerosis and Related Disorders
|February 3, 2020
PubMed
Summary

Long-term immunosuppression for multiple sclerosis (MS) increases infection risks. Immune reconstitution therapies (IRTs) offer a safer alternative, providing long-term disease control with short-term immunosuppression and sustained immunomodulation.

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Ingested (oral) adrenocorticotropic hormone (ACTH) inhibits interleukin-17 in the central nervous system after adoptive transfer of T helper (Th)1/Th17 T cells in the mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis.

Journal of the neurological sciences·2023
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The genealogy, methodology, similarities and differences of immune reconstitution therapies for multiple sclerosis and neuromyelitis optica.

Autoimmunity reviews·2022
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Ingested (Oral) Adrenocorticotropic Hormone Inhibits IL-17 in the Central Nervous System in the Mouse Model of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis.

ImmunoHorizons·2022
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Anti-Inflammatory Agents: An Approach to Prevent Cognitive Decline in Alzheimer's Disease.

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A proposal: How to study pro-myelinating proteins in MS.

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Immune reconstitution therapy in NMOSD.

Multiple sclerosis and related disorders·2021

Area of Science:

  • Immunology
  • Neurology
  • Pharmacology

Background:

  • Multiple sclerosis (MS) treatments often involve prolonged immunosuppression, increasing patient susceptibility to infections and malignancies.
  • Immunosuppression impairs immunosurveillance, the immune system's critical function of detecting pathogens and cancerous cells.

Purpose of the Study:

  • To evaluate the long-term safety and efficacy of disease-modifying therapies (DMTs) in MS.
  • To explore alternative therapeutic strategies that minimize risks associated with prolonged immunosuppression.

Main Methods:

  • Defined immunosuppression as a temporary or permanent alteration of immune function impacting pathogen defense.
  • Contrasted continuous immunosuppressive agents with immune reconstitution therapies (IRTs), which involve short-term administration followed by sustained immunomodulatory effects.

Main Results:

  • IRTs are initially immunosuppressive but become immunomodulatory, offering significant long-term disease activity reduction without continuous retreatment.
  • This approach contrasts with traditional immunosuppressive agents requiring ongoing administration.

Conclusions:

  • Preserving or modulating immunosurveillance is crucial for selecting optimal MS DMTs.
  • For many MS patients, initial immunomodulation followed by IRT for breakthrough disease represents a potentially superior strategy.
  • The paradigm of continuous immunosuppression in MS may be outdated.

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