Neurodegenerative disease treatments by direct TNF reduction, SB623 cells, maraviroc and irisin and MCC950, from an inflammatory perspective - a Commentary

Expert Rev Neurother. 2019 Jun;19(6):535-543. doi: 10.1080/14737175.2019.1618710. Epub 2019 May 24.


Introduction: The importance of excessive cerebral tumor necrosis factor (TNF) concentrations as one of the central tenets of the pathogenesis of the neurodegenerative diseases is now widely known, but variably accepted. Areas covered: Here we update the field by including material that is freely available on the large databases, particularly PubMed. We include the therapeutic outcomes with etanercept (a widely used specific anti-TNF biological), XPro1595 (a new double negative TNF inhibitor), 3,61-dithiothalidomide, implanted SB623 stem cells, maraviroc (a CCR5 inhibitor used to treat AIDS), MCC950 (an NLRP3 inhibitor), and changes in the hormone irisin. Expert opinion: Remarkably, considering the ample literature that links SB623 cells, maraviroc, MCC950 and irisin to TNF, these publications do not mention this cytokine, and therefore not their implicit involvement with controlling its cerebral levels. With regard to developments demonstrated by MCC950, we note that DAMPs and PAMPs recognize and activate both TLRs and inflammasomes in these disease states. Here, as in other illnesses, data suggests that preventing a pathogenic interaction could be achieved through shutting down either of these arms of innate immunity.

Keywords: MCC950; Neurodegenerative disease; SB623 cells; TNF; irisin; maraviroc.

Publication types

  • Review

MeSH terms

  • Animals
  • Fibronectins*
  • Furans
  • Heterocyclic Compounds, 4 or More Rings*
  • Humans
  • Indenes
  • Maraviroc*
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / surgery*
  • Stem Cell Transplantation*
  • Sulfonamides
  • Sulfones*
  • Tumor Necrosis Factor-alpha / drug effects*


  • FNDC5 protein, human
  • Fibronectins
  • Furans
  • Heterocyclic Compounds, 4 or More Rings
  • Indenes
  • Sulfonamides
  • Sulfones
  • Tumor Necrosis Factor-alpha
  • N-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamide
  • Maraviroc