Emerging Therapeutic Applications for Fumarates

Ayla Hoogendoorn; Thomas D Avery; Jiahe Li; Christina Bursill; Andrew Abell; Peter M Grace

doi:10.1016/j.tips.2021.01.004

Emerging Therapeutic Applications for Fumarates

Trends Pharmacol Sci. 2021 Apr;42(4):239-254. doi: 10.1016/j.tips.2021.01.004. Epub 2021 Feb 19.

Authors

Ayla Hoogendoorn¹, Thomas D Avery², Jiahe Li³, Christina Bursill⁴, Andrew Abell², Peter M Grace⁵

Affiliations

¹ Vascular and Heart Health, Life Long Health Theme, South Australian Health and Medical Research Institute, Adelaide, Australia; ARC Centre of Excellence for Nanoscale BioPhotonics, The University of Adelaide, Australia. Electronic address: [email protected].
² ARC Centre of Excellence for Nanoscale BioPhotonics, The University of Adelaide, Australia; Institute for Photonics and Advanced Sensing & Department of Chemistry, The University of Adelaide, Australia.
³ Laboratories of Neuroimmunology, Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴ Vascular and Heart Health, Life Long Health Theme, South Australian Health and Medical Research Institute, Adelaide, Australia; ARC Centre of Excellence for Nanoscale BioPhotonics, The University of Adelaide, Australia; Faculty of Health and Medical Science, University of Adelaide, Adelaide, Australia.
⁵ Laboratories of Neuroimmunology, Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: [email protected].

Abstract

Fumarates are successfully used for the treatment of psoriasis and multiple sclerosis. Their antioxidative, immunomodulatory, and neuroprotective properties make fumarates attractive therapeutic candidates for other pathologies. The exact working mechanisms of fumarates are, however, not fully understood. Further elucidation of the mechanisms is required if these drugs are to be successfully repurposed for other diseases. Towards this, administration route, dosage, and treatment timing, frequency, and duration are important parameters to consider and optimize with clinical paradigms in mind. Here, we summarize the rapidly expanding literature on the pharmacokinetics and pharmacodynamics of fumarates, including a discussion on two recently FDA-approved fumarates Vumerity^TM and Bafiertam^TM. We review emerging applications of fumarates, focusing on neurological and cardiovascular diseases.

Keywords: atherosclerosis; fumarates; ischemia-reperfusion injury; neurodegenerative disease; neuropathic pain.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Fumarates*
Humans
Immunologic Factors
Multiple Sclerosis* / drug therapy

Substances

Fumarates
Immunologic Factors

Grants and funding

RF1 NS113840/NS/NINDS NIH HHS/United States