"A critical issue to consider for potential regenerative therapies for Alzheimer's is the ongoing and progressive burden of brain cell death caused by the disease. It is not sufficient solely to generate new neurons and to promote their survival; it is necessary to reduce the ongoing burden of pathology for there to be long-term benefits for cognition and function," Brinton added. "We were very encouraged to discover that Allo reduced the burden of Alzheimer's pathology. Our latest findings are very exciting as they show that Allo increases the energy capacity of the brain. This is important because the generation of new neurons, new synaptic circuits and synaptic transmission all require substantial energy."Phase 3 Trial of Pioglitazone to Delay Onset of MCI in Cognitively Normal Elderly (1) Uses Genetics to Enrich the Study Population and (2) Is Designed to Verify New Diagnostic Criteria International trials to delay onset of MCI due to Alzheimer's disease are complex in design, requiring careful consideration of case definition, site characteristics, selection of primary outcome metrics and methods to ensure appropriate cultural and psychometric validation. They require innovations in approach to recruit the most appropriate study population, provide consistent MCI diagnoses across countries and to ensure the credibility of their results. Kathleen A. Welsh-Bohmer, Ph.D., of the Joseph and Kathleen Bryan Alzheimer's Disease Research Center at Duke University Medical Center, and her colleagues at Zinfandel and Takeda Pharmaceuticals International, Inc., are currently initiating an international Phase 3 trial of low dose pioglitazone, a medication which at higher doses is approved for treatment of type 2 diabetes, as a therapy to delay onset of MCI due to Alzheimer's. The trial will begin enrollment in 2013. In earlier human studies, treatment with pioglitazone was associated with decreased markers of brain inflammation. Study participants will be cognitively normal individuals who carry genetic risk variations in the APOE and TOMM40 genes that are associated with an increased risk of earlier onset of symptoms of Alzheimer's. By recruiting people with this genetic combination, the researchers believe they will enrich the study population so more participants will get MCI and/or Alzheimer's during the course of the trial.