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J Alzheimers Dis. 2019 Sep 3. doi: 10.3233/JAD-190305. [Epub ahead of print]

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

Author information

1
Division of Neurosurgery, Nanpuh Hospital, Kagoshima, Japan.
2
Division of Clinical Application, Nanpuh Hospital, Kagoshima, Japan.
3
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
4
Department of Gastroenterology and Hepatology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.

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

PMID:
31498121
DOI:
10.3233/JAD-190305

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