Therapeutics

Acitretin

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Overview

Name: Acitretin
Synonyms: Soriatane , Neotigason, RO 101670
Therapy Type: Small Molecule
Target Type: APP and Amyloid-Related (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2)
Company: Stiefel Laboratories, Inc.
Approved for: Psoriasis in US

Background

Acitretin is a retinoid drug used primarily to treat severe psoriasis. It can cause birth defects and other side effects typical of vitamin A overdose, including hair loss, elevated triglyceride levels, and drying of mucosal membranes, and therefore is used only in patients who do not respond to less-toxic psoriasis drugs. Acitretin acts as a retinoic acid receptor agonist. In preclinical models it increases expression of ADAM-10, the physiological α-secretase of the human amyloid precursor protein (APP). Acitretin was reported to boost non-amyloidogenic processing of APP in neuroblastoma cells and reduce Aβ levels in APP/PS-1 transgenic mice (see Tippman et al., 2009). It reportedly crosses the blood-brain barrier in mice (Holthoewer et al., 2012).

Findings

In 2010, a Phase 2 trial began to investigate the efficacy and tolerability of 30 mg/day of acitretin in 76 patients with mild to moderate Alzheimer's disease. The primary outcome was differences in CSF APPSα levels, as measured at four weeks. According to the European Clinical Trials Database Trial Register, this trial has been completed. Results have not been published.

Clinical Trial Timeline

  • Phase 2
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024
NCT01078168
N=76

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References

Paper Citations

  1. . Up-regulation of the alpha-secretase ADAM10 by retinoic acid receptors and acitretin. FASEB J. 2009 Jun;23(6):1643-54. PubMed.
  2. . Acitretin, an enhancer of alpha-secretase expression, crosses the blood-brain barrier and is not eliminated by P-glycoprotein. Neurodegener Dis. 2012;10(1-4):224-8. PubMed.

Further Reading

News

  1. All About ADAM10—The Neuronal α-Secretase
  2. Shedding Assumes α Status

Papers

  1. . Retinoids as a perspective in treatment of Alzheimer's disease. Neurodegener Dis. 2010;7(1-3):190-2. PubMed.