A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of Teprenone in Patients with Alzheimer’s Disease

Article type: Research Article

Authors: Yokoyama, Shunichi^{a; *} | Yoshinaga, Takuma^b | Matsuzaki, Juntaro^c | Suzuki, Hidekazu^d

Affiliations: [a] Division of Neurosurgery, Nanpuh Hospital, Kagoshima, Japan | [b] Division of Clinical Application, Nanpuh Hospital, Kagoshima, Japan | [c] Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan | [d] Department of Gastroenterology and Hepatology, Tokai University School of Medicine, Isehara, Kanagawa, Japan

Correspondence: [*] Correspondence to: Shunichi Yokoyama, MD, PhD, Division of Neurosurgery, Nanpuh Hospital, 14-3 Nagata-cho, Kagoshima-city, 892-8512, Japan. Tel.: +81 99 226 9111; E-mail: [email protected].

Abstract: Background:Teprenone (geranylgeranylacetone), an anti-ulcer agent, has been reported to inhibit amyloid-β increase, senile plaque formation, and neuronal degeneration, and improve memory in mouse models of Alzheimer’s disease (AD). Objective:We conducted a randomized, double-blind, placebo-controlled study to ascertain teprenone’s therapeutic ability for AD. Methods:Patients with mild to moderate AD, with a Mini-Mental State Examination (MMSE) score of 13 to 26, were randomly allocated into two groups depending on the administered drug: donepezil +  placebo (placebo group) and donepezil + teprenone (teprenone group). The primary and secondary endpoints included changes in scores of the Japanese version of the AD Assessment Scale-cognitive subscale (ADAS-J cog) and other evaluations, respectively, including MMSE scores, during a 12-month period after the first administration. Results:Forty-two and thirty-seven patients were allocated to the teprenone and placebo groups, respectively. ADAS-J cog score changes were not different between groups (placebo, 0.6±0.8; teprenone, 0.4±0.8; p = 0.861). However, MMSE scores significantly improved in the teprenone group (placebo, – 1.2±0.5; teprenone, 0.2±0.5; p = 0.044). Subgroup analysis considering the severity of medial temporal area atrophy revealed that this improvement by teprenone was significant in patients with mild (p = 0.013) but not with severe atrophy (p = 0.611). Adverse events were observed in 17.8 and 10.4% of patients in the placebo and teprenone group, respectively. Conclusion:Teprenone may be effective for AD when administered before atrophy progression in the medial temporal areas. Trial Registration:UMIN ID: UMIN000016843

Keywords: Alzheimer’s disease, dementia, donepezil, drug repositioning, geranylgeranylacetone

DOI: 10.3233/JAD-190305

Journal: Journal of Alzheimer's Disease, vol. 71, no. 4, pp. 1187-1199, 2019