BCM-95® (CURCUGREEN®), 29 Mar 2022

Paula Ortiz-Romero, Gustavo Egea, Luis A Pérez-Jurado, Victoria Campuzano

The study investigated the progression of behavioral deficits present in CD (complete deletion) mice, a rodent model of Williams-Beuren syndrome (WBS), a rare neurodevelopmental disorder without any effective treatments.  The test compounds curcumin, verapamil and a combination of both were given as chronic treatments. These compounds have been proven to have beneficial effects over different cognitive aspects of various murine models and thus, may have neuroprotective effects in WBS. Treatment was administered orally dissolved in drinking water. A set of behavioral tests demonstrated the efficiency of combinatorial treatment. Some histological and molecular analyses were performed to analyze the effects of treatment and its underlying mechanism in CD mice. Behavioral improvement correlates with the molecular recovery of several affected pathways regarding MAPK signaling, in tight relation with the control of synaptic transmission. Moreover, CD mice showed an increased activated microglia density in different brain regions, which was prevented by treatment. Therefore, results show that treatment prevented behavioral deficits by recovering altered gene expression in cortex of CD mice, reducing activated microglia and normalizing Bdnf expression levels. These findings unravel the mechanisms underlying the beneficial effects of this novel treatment on behavioral deficits observed in CD mice, and suggest that the combination of curcumin and verapamil could be a potential candidate to treat the cognitive impairments in WBS patients. [Paula Ortiz-Romero, Gustavo Egea1, Luis A Pérez-Jurado, Victoria Campuzano. Verapamil/Curcumin treatment attenuates the behavioral alterations observed in Williams Syndrome mice by regulation of MAPK pathway and Microglia overexpression.

doi: 10.1101/2021.02.01.429086