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 and Jerry R. Colca
Affiliation: Metabolic Solutions Development Company, Kalamazoo, MI, USA
Keywords: Alzheimer’s disease, FDG-PET, insulin resistance, insulin sensitizer, mTOT modulator
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.
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