Kristina Endres1, Falk Fahrenholz2, Johannes Lotz2, Christoph Hiemke2, Stefan Teipel2, Klaus Lieb2, Oliver Tüscher2, Andreas Fellgiebel2. 1. From the Department of Psychiatry and Psychotherapy (K.E., F.F., C.H., K.L., O.T., A.F.), and Institute for Clinical Chemistry and Laboratory Medicine (J.L.), University Medical Centre Johannes Gutenberg University, Mainz; and Department of Psychosomatic Medicine (S.T.), University Medical Centre Rostock, and DZNE, German Centre for Neurodegenerative Diseases, Rostock, Germany. Kristina.Endres@unimedizin-mainz.de. 2. From the Department of Psychiatry and Psychotherapy (K.E., F.F., C.H., K.L., O.T., A.F.), and Institute for Clinical Chemistry and Laboratory Medicine (J.L.), University Medical Centre Johannes Gutenberg University, Mainz; and Department of Psychosomatic Medicine (S.T.), University Medical Centre Rostock, and DZNE, German Centre for Neurodegenerative Diseases, Rostock, Germany.
Abstract
OBJECTIVE: We investigated induction of α-secretase A disintegrin and metalloprotease 10 (ADAM10) by the synthetic retinoid acitretin (Neotigason; Actavis, München-Riem, Germany) in patients with mild to moderate Alzheimer disease (AD) via measurement of CSF content of α-secretase-derived amyloid precursor protein (APPs-α). METHODS:Twenty-one patients clinically diagnosed with mild to moderate AD received acitretin (30 mg per day) or placebo in a 4-week double-blind study. Primary endpoint was the difference of CSF APPs-α ratios calculated from the APPs-α levels after treatment and at baseline. We monitored safety and tolerability of the treatment. In addition, we assessed biomarkers such as β-amyloid 42 (Aβ42) under treatment conditions. RESULTS: The acitretin group showed a significant increase in CSF APPs-α levels compared with the placebo group (difference 0.38, 95% confidence interval 0.03-0.72, p = 0.035) within this rather short treatment period. The synthetic retinoid acitretin was overall safe and well tolerated. CONCLUSIONS: Our pilot study highlights that acitretin is able to enhance the nonamyloidogenic APP processing in human patients. Clinical consequences of this regulation should be investigated in larger and longer trials in patients with AD to evaluate acitretin's potential to serve as a novel therapeutic drug. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in patients with AD, oral acitretin increases CSF APPs-α levels.
RCT Entities:
OBJECTIVE: We investigated induction of α-secretase A disintegrin and metalloprotease 10 (ADAM10) by the synthetic retinoidacitretin (Neotigason; Actavis, München-Riem, Germany) in patients with mild to moderate Alzheimer disease (AD) via measurement of CSF content of α-secretase-derived amyloid precursor protein (APPs-α). METHODS: Twenty-one patients clinically diagnosed with mild to moderate AD received acitretin (30 mg per day) or placebo in a 4-week double-blind study. Primary endpoint was the difference of CSF APPs-α ratios calculated from the APPs-α levels after treatment and at baseline. We monitored safety and tolerability of the treatment. In addition, we assessed biomarkers such as β-amyloid 42 (Aβ42) under treatment conditions. RESULTS: The acitretin group showed a significant increase in CSF APPs-α levels compared with the placebo group (difference 0.38, 95% confidence interval 0.03-0.72, p = 0.035) within this rather short treatment period. The synthetic retinoidacitretin was overall safe and well tolerated. CONCLUSIONS: Our pilot study highlights that acitretin is able to enhance the nonamyloidogenic APP processing in humanpatients. Clinical consequences of this regulation should be investigated in larger and longer trials in patients with AD to evaluate acitretin's potential to serve as a novel therapeutic drug. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in patients with AD, oral acitretin increases CSF APPs-α levels.
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