title: An evaluation of MSDC-0160, a prototype mTOT modulating insulin sensitizer, in patients with mild Alzheimer's disease.
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.
authors.forename: Raj C
authors.initials: RC
authors.lastname: Shah
authors.forename: Dawn C
authors.initials: DC
authors.lastname: Matthews
authors.forename: Randolph D
authors.initials: RD
authors.lastname: Andrews
authors.forename: Ana W
authors.initials: AW
authors.lastname: Capuano
authors.forename: Debra A
authors.initials: DA
authors.lastname: Fleischman
authors.forename: James T
authors.initials: JT
authors.lastname: VanderLugt
authors.affiliation: Metabolic Solutions Development Company, Kalamazoo, MI, USA. jcolca@msdrx.com.
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Colca
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D001931:Brain Mapping; D002491:Central Nervous System Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D019275:Radiopharmaceuticals; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D002491:Central Nervous System Agents; C581095:MSDC-0160; D011725:Pyridines; D019275:Radiopharmaceuticals; D045162:Thiazolidinediones; D019788:Fluorodeoxyglucose F18; D005947:Glucose