Glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide analogues as novel treatments for Alzheimer’s and Parkinson’s disease

Abstract

Type 2 diabetes is a risk factor for developing chronic neurodegenerative disorders such as Alzheimer’s disease (AD) or Parkinson’s disease (PD). The underlying mechanism appears to be insulin desensitization in the brain. A range of glucagon-like peptide 1 (GLP-1) mimetics and glucose-dependent insulinotropic polypeptide (GIP) analogues initially designed to treat diabetes protected transgenic animals that model AD and toxin-based animal models of PD. Novel dual GLP-1/GIP analogues also show good neuroprotective effects. On the basis of these findings, first clinical trials have been conducted. In a pilot study on patients with AD, the GLP-1 analogue liraglutide showed good protective effects in 18F-fluorodeoxyglucose (18F-FDG)-PET brain imaging. It was found that the disease-related decay of brain activity had been completely stopped by the drug. In a pilot study in patients with PD, the GLP-1 mimetic exendin-4 showed good protection from motor and cognitive impairments. These results demonstrate the potential of developing disease-modifying treatments for AD and PD.