KALAMAZOO (WWJ) – Metabolic Solutions Development Co. LLC announced that Jerry Colca, co-founder and chief scientific officer of MSDC, presented results of a Phase 2a study at the 14th International Conference on Alzheimer’s Drug Discovery.
In people with dementia due to Alzheimer’s disease who were not diabetic, the study found that the mTOT-modulating insulin sensitizer, MSDC-0160, maintained glucose metabolism in key regions of the brain associated with cognitive decline due to Alzheimer’s Disease, as confirmed by FDG-PET imaging.
Glucose is a major energy source for cells, and alterations in glucose metabolism by nerve cells (neurons) in the brain have been associated with Alzheimer’s Disease pathology. Also, reduced brain glucose metabolism is region-specific. In this study, in participants treated with placebo, the measure of glucose uptake significantly declined in key regions of the brain associated with cognitive decline in persons with dementia due to Alzheimer’s disease. But this did not occur in the subjects treated with MSDC-0160.
“We are in urgent need of new approaches in Alzheimer’s drug research because there are currently no approved therapies to halt or even slow progression of the disease,” said Howard Fillit, M.D., executive cirector and chief science officer of the Alzheimer’s Drug Discovery Foundation. “The mitochondrially-targeted insulin sensitizers are an exciting new class of drugs in Alzheimer’s disease. The current results provide the basis for further clinical investigation of MSDC-0160 in Alzheimer’s patients.”
Colca presented study findings Monday in a session covering “Mitochondrial Function and Neuroinflammation.” The conference, which took place in Jersey City, N.J., is presented by the Alzheimer’s Drug Discovery Foundation, which supported the Phase 2a research with grant funding. The study was conducted at Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago. Image data analysis was performed by Abiant Inc. of Grayslake, Ill.
“This study suggests that we should press forward to continue to evaluate this novel class of mitochondrially-targeted insulin sensitizers in AD,” Colca said. “MSDC is most appreciative of the financial support provided by ADDF, without which completion of this clinical trial would not have been possible.”
It is estimated that 5.2 million people in the United States have dementia due to Alzheimer’s. By 2050, the number of individuals worldwide living with dementia due to Alzheimer’s is anticipated to increase from 36 million to 115 million people — with two-thirds living in developing countries. Given the worldwide public health impact of Alzheimer’s, increased efforts are needed to develop new and effective interventions which have the potential to be used early in the course of the disease when intervention may have the most impact.
Alzheimer’s has been characterized as “type 3 diabetes.” While the development of Alzheimer’s Disease involves brain cell loss associated with the build-up of abnormal clusters of protein fragments called plaques, and dead and dying nerve cells that contain twisted strands of another protein called tau, other mechanisms also may play a role. Reduced glucose metabolism associated with Alzheimer’s has been tied with a progressive loss of mitochondrial function and altering mitochondrial dysfunction has been postulated as a target for the treatment of AD together with treatment of insulin resistance — a root cause of type 2 diabetes. MSDC has identified a new drug target of insulin sensitizers.
The drug candidate MSDC-0160, a prototype mTOT modulator developed by MSDC, exerts its insulin-sensitizing effects through a recently identified new drug target located in the inner mitochondrial membrane. Data suggest mTOT functions as a molecular sensor switch that coordinates carbohydrate, lipid and amino acid metabolism with cell function. In addition to preserving b-cell function as observed in human islets, mTOT modulators have been shown in animal models of type 2 diabetes to improve insulin signaling, decrease calorie-storing “white fat,” and increase levels of calorie burning “brown fat.”
Recently published Phase 2b clinical data from a study in 258 type 2 diabetic patients further demonstrate modulating mTOT could constitute a new approach for the discovery and development of potentially more useful and novel insulin sensitizers.
Funding of both preclinical work and the current clinical study by the Alzheimer’s Drug Discovery Foundation has allowed MSDC to test the potential of MSDC-0160 in Alzheimer’s Disease.
More at http://www.msdrx.com.
