An evaluation of MSDC-0160, a prototype mTOT modulating insulin sensitizer, in patients with mild Alzheimer's disease

Raj C Shah, Dawn C Matthews, Randolph D Andrews, Ana W Capuano, Debra A Fleischman, James T VanderLugt, Jerry R Colca, Raj C Shah, Dawn C Matthews, Randolph D Andrews, Ana W Capuano, Debra A Fleischman, James T VanderLugt, Jerry R Colca

Abstract

Alzheimer's disease (AD) is associated with insulin resistance and specific regional declines in cerebral metabolism. The effects of a novel mTOT modulating insulin sensitizer (MSDC-0160) were explored in non-diabetic patients with mild AD to determine whether treatment would impact glucose metabolism measured by FDG-PET in regions that decline in AD. MSDC-0160 (150 mg once daily; N=16) compared to placebo (N=13) for 12 weeks did not result in a significant difference in glucose metabolism in pre-defined regions when referenced to the pons or whole brain. However, glucose metabolism referenced to cerebellum was maintained in MSDC-0160 treated participants while it significantly declined for placebo patients in anterior and posterior cingulate, and parietal, lateral temporal, medial temporal cortices. Voxel-based analyses showed additional differences in FDG-PET related to MSDC-0160 treatment. These exploratory results suggest central effects of MSDC-0160 and provide a basis for further investigation of mTOT modulating insulin sensitizers in AD patients.

Figures

Fig. (1)
Fig. (1)
Effect on change in FDG-PET, representative views from sagittal, coronal, and transaxial aspects, referenced to the cerebellum. Significant clusters from with-in group and subtraction analyses relative to cerebellar gray reference region are superimposed on selected transaxial MRI template slices. Blue indicates a decrease in glucose metabolism over the treatment period relative to the reference region, and red a relative increase (or preservation). The placebo group showed an AD-like pattern of decline that was absent in the MSDC-0160 group. The lower panel is a subtraction to show the relative effect of the MSDC-0160 treatment.
Fig. (2)
Fig. (2)
Overview of voxel based analyses using three reference regions. Significant clusters fromwithin-group analyses were superimposed on selected transaxial MRI template slices.Blue indicates a decrease in glucose metabolism over the treatment period relative to the reference region, and red a relative increase (or preservation). While the Placebo group exhibited an AD-like pattern of decline (and relative preservation), the MSDC-0160 group showed relative increases in regions including parahippocampus when referenced to whole brain and cerebellum, and decreases most evident in frontal and cerebellar gray regions when referenced to pons.

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