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Bryostatin-1 alleviates experimental multiple sclerosis.

Michael D Kornberg1, Matthew D Smith1, Hasti Atashi Shirazi2

  • 1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287.

Proceedings of the National Academy of Sciences of the United States of America
|February 15, 2018
PubMed
Summary
This summary is machine-generated.

Bryostatin-1 shows significant therapeutic potential for multiple sclerosis (MS) by reducing central nervous system inflammation. This compound effectively reverses neurological deficits in an MS animal model, even in late-stage disease.

Keywords:
EAEbryostatinmultiple sclerosisneuroimmunology

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Area of Science:

  • Neuroimmunology
  • Pharmacology
  • Inflammatory Diseases

Background:

  • Multiple sclerosis (MS) is a chronic inflammatory CNS disorder.
  • Progressive MS lacks effective treatments, driven by CNS-localized inflammation and myeloid cell activation.
  • Bryostatin-1 (bryo-1) is a CNS-permeable compound with a known safety profile, shown to modulate T-helper cell differentiation.

Purpose of the Study:

  • To investigate the therapeutic potential of bryostatin-1 (bryo-1) in experimental autoimmune encephalomyelitis (EAE), a model for MS.
  • To evaluate bryo-1's efficacy in both preventive and therapeutic settings of EAE.
  • To explore bryo-1's effects on innate immune cells in the context of MS.

Main Methods:

  • Administration of bryostatin-1 (bryo-1) to EAE mice for preventive and therapeutic treatment.
  • Assessment of neurological deficits and disease progression in treated EAE mice.
  • In vitro analysis of bryo-1's effects on antigen-presenting cells (APCs) and lymphocytes.

Main Results:

  • Bryostatin-1 (bryo-1) treatment abolished neurological deficits when administered preventively in EAE.
  • Bryo-1 significantly reversed established neurological deficits in EAE, even when treatment was initiated late in the disease course.
  • In vitro, bryo-1 promoted an anti-inflammatory phenotype in dendritic cells and macrophages.

Conclusions:

  • Bryostatin-1 (bryo-1) demonstrates significant therapeutic benefits in an MS animal model, suggesting potential for MS treatment.
  • Bryo-1's efficacy in late-stage EAE and its modulation of innate myeloid cells indicate potential for progressive MS.
  • The established clinical safety profile of bryo-1 supports its further investigation as an MS therapeutic agent.