A Double Blind, Placebo-controlled, Randomized, 15-day Treatment, Pharmacodynamics, Safety, and Pharmacokinetics Study of THN201 Versus Donepezil Administered Orally to Healthy Male Volunteers Including a Scopolamine Challenge

This study explores the safety, pharmacodynamics and pharmacokinetics of THN201 a combination of donepezil and mefloquine to improve cognitive function in healthy male volunteers after impairment by a scopolamine challenge.

Start Date27 Sep 2018

Sponsor / Collaborator

Theranexus SA

100 Clinical Results associated with Donepezil Hydrochloride/Mefloquine Hydrochloride

100 Translational Medicine associated with Donepezil Hydrochloride/Mefloquine Hydrochloride

100 Patents (Medical) associated with Donepezil Hydrochloride/Mefloquine Hydrochloride

Literatures (Medical) associated with Donepezil Hydrochloride/Mefloquine Hydrochloride

Frontiers in NeuroscienceQ3 · MEDICINE

Efficacy of THN201, a Combination of Donepezil and Mefloquine, to Reverse Neurocognitive Deficits in Alzheimer’s Disease

Q3 · MEDICINE

ArticleOA

Author: Portal, Benjamin ; Déglon, Nicole ; Villard, Vanessa ; Picoli, Christèle ; Mouthon, Franck ; Meunier, Johann ; Duchêne, Adeline ; Lejards, Camille ; Droguerre, Marine ; Charvériat, Mathieu ; Guiard, Bruno P ; Hamon, Michel

Donepezil (DPZ) is an acetylcholinesterase inhibitor used in Alzheimer's disease to restore cognitive functions but is endowed with limited efficacy. Recent studies pointed out the implication of astroglial networks in cognitive processes, notably via astrocyte connexins (Cxs), proteins involved in gap junction intercellular communications. Hence, we investigated the impact on cognition of pharmacological or genetic modulations of those astrocyte Cxs during DPZ challenge in two rodent models of Alzheimer's disease-like memory deficits. We demonstrated that the Cx modulator mefloquine (MEF) significantly enhanced the procognitive effect of DPZ in both models. In parallel, we determined that MEF potentiated DPZ-induced release of acetylcholine in hippocampus. Finally, local genetic silencing of astrocyte Cxs in the hippocampus was also found to enhance the procognitive effect of DPZ, pointing out the importance of Cx-dependent astrocyte networks in memory processes.

Frontiers in NeuroscienceQ3 · MEDICINE

Pharmaco-fUS for Characterizing Drugs for Alzheimer’s Disease – The Case of THN201, a Drug Combination of Donepezil Plus Mefloquine

Q3 · MEDICINE

ArticleOA

Author: Droguerre, Marine ; Hamon, Michel ; Valdebenito, Marco ; Charvériat, Mathieu ; Vidal, Benjamin ; Mouthon, Franck ; Zimmer, Luc

Donepezil is a potent acetylcholinesterase inhibitor, largely used worldwide to alleviate cognitive symptoms in Alzheimer's disease (AD). Beyond the widely described neuronal impact of donepezil, it was recently shown that targeting connexins, the proteins involved in astrocyte network organization, potentiates donepezil efficacy profile using behavioral tests in AD rodent models. We herein present data demonstrating the potential of functional ultrasound imaging to monitor cerebral activity changes after pharmacological challenge in mice. As an example, we showed that although administration of donepezil or mefloquine alone at low dose had only very limited effects on the signal compared to the baseline, their combination produced marked hemodynamic effects in the hippocampus, in line with previously published behavioral data demonstrating a synergic interaction between both drugs. Thus, the present study provides new perspectives, (i) through the use of pharmaco-fUS, a new non-clinical imaging modality, to move forward drug discovery in AD and (ii) by the profiling of two drug treatments on brain dynamics, one used in AD: donepezil, and the other in development: donepezil combined with mefloquine (THN201) as a modulator of astrocyte network.

100 Deals associated with Donepezil Hydrochloride/Mefloquine Hydrochloride

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	Phase 1	FR	Theranexus SA	27 Sep 2018
Cognitive Dysfunction	Phase 1	FR	Theranexus SA	27 Sep 2018

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


AAIC2012	Not Applicable	Alzheimer Disease	433	Donepezil 23 mg/day	vzkncnpbyv(aonmjcdshd): treatment difference = 1.4 (95% CI, 0.57 - 2.32), P-Value = 0.0013	Positive	01 Jul 2012
				Donepezil 10 mg/day
AAIC2011	Not Applicable	Alzheimer Disease	570	Donepezil 23 mg/day	pvrnkbfcfo(mgtnkgtwvf) = 13.9% ikvrateasw (pyryfvhjqu ) View more	Positive	01 Jul 2011
AAIC2010	Not Applicable	Dementia, Vascular	34	Donepezil 5mg/day	meousospdb(vuudusghhd) = uaosqjsvol ktnhyiuswh (hedyanvkqt )	Positive	01 Jul 2010
				Donepezil 10mg/day	meousospdb(vuudusghhd) = qmgvkpulmr ktnhyiuswh (hedyanvkqt )
AZ3106242 (AAIC2008)	Not Applicable	Alzheimer Disease	197	SB-742457 15mg/day titrated to 35 mg/day	(xkaioarokd) = tnvbpiabgl oowodmpqsn (rszcjqofyf )	-	01 Jul 2008
				Donepezil 5mg/day titrated to 10 mg/day	(xkaioarokd) = yekbogupsv oowodmpqsn (rszcjqofyf )

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