Levamisole derivatives as immune modulators for the treatment of amyotrophic lateral sclerosis (ALS)

Future Med Chem. 2023 Apr;15(8):651-659. doi: 10.4155/fmc-2023-0028. Epub 2023 May 12.

Abstract

Aim: To discover derivatives of the anthelmintic drug levamisole, which has been reported to possess immune-modulatory properties, as treatments for amyotrophic lateral sclerosis (ALS), which has been suggested to be in part an autoimmune disease. Results: We have synthesized ten analogs of the racemic version of levamisole, tetramisole, as well as eleven analogs on a related system. All of the analogs have been tested for their ability to affect the response of five ALS-relevant cytokines. Conclusion: We have discovered a number of interesting derivatives that have encouraging cytokine response data and good metabolic stability, with the potential to have a positive impact on ALS either as single agents, or in combination.

Keywords: ALS; amyotrophic lateral sclerosis; cytokine response; immune modulation; levamisole.

Plain language summary

Aim: To discover derivatives of the antiparasitic worm drug levamisole, which has been reported to be able to modulate the immune response, as treatments for amyotrophic lateral sclerosis (ALS), which has been suggested to be in part an autoimmune disease. Results: We have synthesized ten analogs of a variation of levamisole, tetramisole, as well as 11 analogs on a related system. All of the analogs have been tested for their ability to affect the response of five ALS-relevant immune-modulatory substances (cytokines). Conclusion: We have discovered a number of interesting derivatives that have encouraging cytokine response data and good metabolic stability, with the potential to have a positive impact on ALS either as single agents, or in combination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis* / drug therapy
  • Amyotrophic Lateral Sclerosis* / metabolism
  • Cytokines / metabolism
  • Humans
  • Levamisole / pharmacology
  • Levamisole / therapeutic use
  • Tetramisole / therapeutic use

Substances

  • Levamisole
  • Cytokines
  • Tetramisole