Phenserine Efficacy in Alzheimer's Disease

Article type: Research Article

Authors: Winblad, Bengt^a | Giacobini, Ezio^b | Frölich, Lutz^c | Friedhoff, Lawrence T.^d | Bruinsma, Gosse^e | Becker, Robert E.^{f; g} | Greig, Nigel H.^{g; *}

Affiliations: [a] Alzheimer's Disease Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden | [b] Department of Rehabilitation and Geriatrics, University of Geneva, Medical School, University Hospitals of Geneva, Thonex-Geneva, Switzerland | [c] Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany | [d] Pharmaceutical Special Projects Group, LLC, River Vale, NJ, USA | [e] Ciurem Pharma BV, Leiden, Netherlands | [f] Aristea Translational Medicine Corporation, Freeport, ME, USA | [g] Drug Design & Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA

Correspondence: [*] Correspondence to: Nigel H. Greig, Drug Design and Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA. E-mail: Greign@mail.nih.gov.

Abstract: To gather preliminary evidence in Alzheimer's disease (AD) for the efficacy of phenserine, a non-competitive acetylcholinesterase inhibitor that has independent modulatory effects on amyloid-β generation, a 12-week comparison of patients receiving phenserine (10 and 15 mg BID) or placebo was conducted under double-blind conditions. Patients who completed 12 weeks of the double-blind before others were continued in the double-blind to determine longer-term treatment effects. At 12 weeks, mean ADAS-cog (AD assessment scale-cognitive) changes from baseline were −2.5 and −1.9 for high-dose phenserine (n = 83) and placebo (n = 81) groups, respectively, a non-statistically significant improvement for the high-dose phenserine group relative to placebo. CIBIC+ (clinician's interview based impression of change + caregiver's input) values for the high-dose and placebo groups were similar at 12 weeks. For patients who received more than 12 weeks of therapy, the ADAS-cog changes were −3.18 and −0.66 for the high-dose phenserine (n = 52) and placebo (n = 63) groups, respectively, a difference achieving statistical significance (p = 0.0286). After 12 weeks, CIBIC+ values were 3.59 and 3.95 for the high-dose (n = 54) and placebo (n = 66) groups respectively (p = 0.0568). These results from this short-term study are consistent with phenserine potentially benefiting mild to moderate Alzheimer's disease symptomatically but do not address possible amyloid metabolic mediated effects on disease processes in AD.

Keywords: Acetylcholinesterase, Alzheimer's disease, Alzheimer clinical trial, amyloid-β peptide, amyloid-β protein precursor, cholinesterase inhibitor, phenserine

DOI: 10.3233/JAD-2010-101311

Journal: Journal of Alzheimer's Disease, vol. 22, no. 4, pp. 1201-1208, 2010