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.
Keywords: Alzheimer’s disease, FDG-PET, insulin resistance, insulin sensitizer, mTOT modulator.
Current Alzheimer Research
Title:An Evaluation of MSDC-0160, A Prototype mTOT Modulating Insulin Sensitizer, in Patients with Mild Alzheimer's Disease
Volume: 11 Issue: 6
Author(s): Raj C. Shah, Dawn C. Matthews, Randolph D. Andrews, Ana W. Capuano, Debra A. Fleischman, James T. VanderLugt and Jerry R. Colca
Affiliation:
Keywords: Alzheimer’s disease, FDG-PET, insulin resistance, insulin sensitizer, mTOT modulator.
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.
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Cite this article as:
Shah C. Raj, Matthews C. Dawn, Andrews D. Randolph, Capuano W. Ana, Fleischman A. Debra, VanderLugt T. James and Colca R. Jerry, An Evaluation of MSDC-0160, A Prototype mTOT Modulating Insulin Sensitizer, in Patients with Mild Alzheimer's Disease, Current Alzheimer Research 2014; 11 (6) . https://dx.doi.org/10.2174/1567205011666140616113406
DOI https://dx.doi.org/10.2174/1567205011666140616113406 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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