Synonyms: Soriatane , Neotigason, RO 101670
Therapy Type: Small Molecule
Target Type: 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
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).
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
- Tippmann F, Hundt J, Schneider A, Endres K, Fahrenholz F. Up-regulation of the alpha-secretase ADAM10 by retinoic acid receptors and acitretin. FASEB J. 2009 Jun;23(6):1643-54. PubMed.
- Holthoewer D, Endres K, Schuck F, Hiemke C, Schmitt U, Fahrenholz F. 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. Epub 2012 Feb 1 PubMed.
- Fahrenholz F, Tippmann F, Endres K. Retinoids as a perspective in treatment of Alzheimer's disease. Neurodegener Dis. 2010;7(1-3):190-2. PubMed.