Bexarotene and Its Potential Role in the Treatment of Neurological Disorders: Beyond Its Role as an Anti-Cancer Agent

March 2014 | Volume 13 | Issue 3 | Editorials | 240 | Copyright © 2014

Shailendra Kapoor MD

Patterson Avenue Family Practice, Schaumburg, IL

Abstract

No abstract available

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I read with great interest the recent article by Huang et al,1 bexarotene (BEX) may also have potent benefits for the treatment of various neurological disorders.

For instance, recent data suggests that BEX may be of potential benefit in the treatment of Alzheimer’s disease.2 Landreth et al, have recently shown that BEX markedly accentuates the clearance of β-amyloid peptides from the brain.3 This accentuated clearance is Apo-E dependent.4 It is also LXR and PPAR-γ dependent. Similarly, Cramer et al, have shown that β-amyloid plaque formation5,6 is significantly attenuated by BEX.7 In fact, they reported that within a time span as short as 72 hours, the β-amyloid plaque burden was attenuated and reduced by almost half. The net result is that neuro- cognitive deterioration is significantly restricted and reversed to some extent.7,8 Simultaneous improvement in the functioning of neural networks is seen which further mitigates Alzheimer’s disease like cognitive decline.9,10 A similar impact is seen on olfactory deficits noted in animal models of Alzheimer’s disease.

Recent data also suggests that BEX may be of clinical benefit in Parkinson’s disease.11 For instance, McFarland et al have recently demonstrated that BEX administration helps in restoring dopaminergic function in 6- hydroxydopamine lesioned animal models.10 At the same time, it reverses behavioral deficits noted in these animal models. BEX mediates this role by virtue of its interaction with Nurr1-RXR12 heterodimers.6 Interestingly, these neuro-protective effects of BEX are seen at doses that are almost hundred times less than its doses used in cancer treatment.3,9

“Recent data also suggests that BEX may be of clinical benefit in Parkinson’s disease.”

As is obvious from the above examples BEX has shown considerable promise so far as a possible agent for the treatment of neurological disorders. Hopefully, the coming few years will see increased research into this aspect of BEX.

Disclosure

The author has no relevant conflicts to disclose.

References

  1. Huang J, Cowper S, Moss J, Girardi M. Case Experience of 308-nm Excimer Laser Therapy Compatibility With PUVA and Oral Bexarotene for the Treatment of Cutaneous Lesions in Mycosis Fungoides. J Drugs Dermatol. 2013;12:487-9.
  2. Wildsmith KR, Holley M, Savage JC, Skerrett R, Landreth GE. Evidence for impaired amyloid β clearance in Alzheimer's disease. Alzheimers Res Ther. 2013 12;5(4):33.
  3. Landreth GE, Cramer PE, Lakner MM, et al. E-mail a link to this item to a friend or colleague: Response to Comments on “ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models”. Science. 2013;24:924.
  4. Rohn TT. Proteolytic Cleavage of Apolipoprotein E4 as the Keystone for the Heightened Risk Associated with Alzheimer’s Disease. Int J Mol Sci. 2013;14:14908-22.
  5. Veeraraghavalu K, Zhang C, Miller S, et al. Comment on “ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models”. Science. 2013;340:924-.
  6. Veeraraghavalu K, Zhang C, Miller S, et al. Comment on “ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models”. Science. 2013;340:924-.
  7. Cramer PE, Cirrito JR, Wesson DW, et al. ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models. Science. 2012;335:1503-6.
  8. Choi S, Aid S, Caracciolo L, et al. Cyclooxygenase-1 inhibition reduces amyloid pathology and improves memory deficits in a mouse model of Alzheimer's disease. J Neurochem. 2013;124:59-68.
  9. Ulrich JD, Burchett JM, Restivo JL, et al. In vivo measurement of apolipoprotein E from the brain interstitial fluid using microdialysis. Mol neurodegener. 2013;8:1-7.
  10. McFarland K, Spalding TA, Hubbard D, Ma J, Olsson R, Burstein ES. Low Dose Bexarotene Treatment Rescues Dopamine Neurons and Restores Behavioral Function in Models of Parkinson’s Disease. ACS Chem Neurosci. 2013; 4(11):1430–1438
  11. Tabarés-Seisdedos R, Rubenstein JL. Inverse cancer comorbidity: a serendipitous opportunity to gain insight into CNS disorders. Nat Rev Neurosci. 2013;14(4):293-304.
  12. Fernández-Borges N, Eraña H, Elezgarai SR, Harrathi C, Gayosso M, Castilla J. Infectivity versus Seeding in Neurodegenerative Diseases Sharing a Prion-Like Mechanism. Int J Cell Biol. 2013;2013.

AUTHOR CORRESPONDENCE

Shailendra Kapoor MD

E-mail: shailendrakapoor@yahoo.com

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