Alzheimer’s Stem Cell Research
PNR&D scientists have conducted Food and Drug Administration-approved human clinical trials in amyotrophic lateral sclerosis (ALS) patients. Now, the PNR&D is working to develop a similar breakthrough treatment for Alzheimer’s disease (AD). In collaboration with Neuralstem Inc., we have developed unique enhanced lines of human neural stem cells that produce several neuroprotective factors and can differentiate into neuronal and glial cell types. Initial pilot studies have demonstrated that we can accurately deliver stem cells to therapeutic target areas of the brain and that transplanted cells survive for several weeks in the AD brain. More recent efficacy studies in a model of early-onset AD show that delivery of human neural stem cells directly to the brain improves memory and learning deficits and reduces the buildup of amyloid plaques. PNR&D’s recent National Institute on Aging U01 award has enabled further study of cellular transplantation in additional AD models that recapitulate many of the characteristics observed in AD patients, to determine exactly how these stem cells impact disease processes and cognition. The U01 grant will also fund large animal studies to analyze safety and feasibility of stem cell transplantation, as well as innovative MRI-based cell tracking methods for live imaging of transplanted stem cells within the brain. These exciting studies will follow a similar preclinical pipeline that was developed by PNR&D to progress the ALS stem cell therapy to an FDA-approved clinical trial.
- Human cortical neural stem cells expressing insulin-like Growth Factor-I: A Novel Cellular Therapy for Alzheimer’s Disease (Stem Cells Translational Medicine; March 5, 2016)
- Human neural stem cell transplantation into the corpus callosum of Alzheimer’s mice (Annals of Clinical and Translational Medicine; August 18, 2017)
Ties Between Diabetes and Alzheimer’s Disease
Current research in the PNR&D is focused on investigating the mechanisms that link diabetes and Alzheimer’s disease using both cellular and animal models. Two of the most prominent pathological characteristics of Alzheimer’s disease are the accumulation of β-amyloid in extracellular plaques and the appearance of intracellular neurofibrillary tangles. Results indicate that tau, one of the major components of the tangles, is abnormally regulated during hyperglycemic conditions in cell culture systems and in diabetic animals. Therefore, PNR&D investigators are trying to develop new animal models to study the mechanisms underlying the interaction of these two pandemic diseases. Successful study completions will provide a fundamental basis for drug development and lifestyle modifications aimed at treating and/or preventing diabetes and Alzheimer’s disease.
Alzheimer’s Disease Progression Due to Insulin Resistance
PNR&D investigators are working to understand how obesity-related insulin resistance in neurons impacts cognitive impairment and Alzheimer’s disease pathology, like β-amyloid extracellular plaques and intracellular neurofibrillary tangles containing tau. A better understanding of this relationship will aid in the development of much-needed therapies to treat and prevent Alzheimer’s disease onset and progression in obese or diabetic individuals.
Obesity is one of the greatest risk factors for diabetes and currently close to one-third of adults in the United States are obese. Obesity is accompanied by impaired fat metabolism and impaired insulin signaling or resistance. This insulin resistance occurs in various tissues, including neurons. Impaired insulin signaling is also associated with cognitive impairment and Alzheimer’s disease. In fact, impaired insulin signaling impacts the expression and metabolism of the proteins β-amyloid and tau, which become hallmark components of the brain pathology that characterizes Alzheimer’s disease.