As the Alzheimer's disease (AD) population is growing rapidly, currently there are no cure treatments. The goal of this resubmitted STTR proposal is to conduct a preclinical study with pramlintide to prove a potential treatment for AD. We have revised the proposal significantly according to the reviewers' comments. Pramlintide is an FDA approved drug for diabetes and is an amylin analog. As diabetes increases the risk of AD, diabetic medications like pramlintide may be beneficial for AD as an off-label drug. Additionally, our preliminary study also suggests that amylin analogs may remove the neurotoxic amyloid-? peptide (A?) out of the AD brain. It is therefore imperative to study whether amylin and its analogs can be used as a drug for the treatment of AD. The goal of this STTR proposal is to evaluate the effect of pramlintide on the amyloid precursor protein transgenic (APP) mice, an AD mouse model. The central hypothesis of this study is that the pramlintide injection will provoke an increase of A? in the blood, and the pramlintide treatment will reduce A? from the brain into blood to improve cognitive impairment in the APP transgenic mice. The APP mice will be treated with one dose of pramlintide on a daily basis, and will be conducted to assess improved movement, coordination and learning capabilities. We will evaluate and compare the levels of soluble and precipitated A? in the cortex and hippocampus in the brains treated by the drug vs. placebo. We will also examine glucose metabolic biomarkers and tau/p-tau levels in the brains.
Thesaurus Terms: Alternative Treatment;Alzheimer's Disease;Alzheimer's Disease Risk;Amino Acids;Amyloid;Amyloid Beta-Protein;Amyloid Beta-Protein Precursor;Amyloid Pathology;Analog;Appetite Regulation;Base;Behavior Test;Binding (Molecular Function);Biological Markers;Blood;Blood - Brain Barrier Anatomy;Brain;Brain Tissue;Cerebrospinal Fluid;Chronic;Clinical;Clinical Treatment;Clinical Trials;Cognition;Cost;Diabetes Mellitus;Diabetic;Disease Diagnosis;Dose;Elderly;Excision;Fda Approved;Glucose;Glucose Metabolism;Goals;Health;Hippocampus (Brain);Human;Impaired Cognition;Improved;Injection Of Therapeutic Agent;Insulin Resistance;Insulinase;Intraperitoneal Injections;Islet Amyloid Polypeptide;Label;Learning;Legal Patent;Measures;Memory;Metabolic;Mild Cognitive Impairment;Mouse Model;Movement;Mus;Neurotoxic;Non-Insulin-Dependent Diabetes Mellitus;Pancreas;Pathology;Patients;Peptides;Pharmaceutical Preparations;Phase Iii Clinical Trials;Pilot Trial;Placebos;Plasma;Population;Pramlintide;Pre-Clinical;Preclinical Study;Prevent;Published Comment;Receptor;Safety;Sampling;Senile Plaques;Serum;Small Business Technology Transfer Research;Spinal Puncture;Symptoms;Tau Proteins;Time;Transgenic Mice;Transgenic Organisms;Wild Type Mouse;
