Insulin, incretins and other growth factors as potential novel treatments for Alzheimer's and Parkinson's diseases

Abstract

Recently, it has been shown that in patients with AD (Alzheimer's disease) and, to some degree, in patients with PD (Parkinson's disease) insulin signalling is impaired. This finding has initiated a range of research projects that showed remarkable improvements using treatments that initially had been developed to treat diabetes. Pre-clinical studies showed good neuroprotective effects when applying insulin or long-lasting analogues of incretin peptides. In transgenic animal models of AD and PD, analogues of the incretin GLP-1 (glucagon-like peptide 1) prevented neurodegenerative processes and improved neuronal and synaptic functionality in AD and PD. Amyloid plaque load and synaptic loss as well as cognitive impairment had been ameliorated in AD models, and dopaminergic loss of transmission and motor function was reversed in models of PD. On the basis of these promising findings, several clinical trials are being conducted with the first encouraging clinical results being published. In several pilot studies in AD patients, the nasal application of insulin showed encouraging effects on cognition and biomarkers. A pilot study in PD patients testing a GLP-1 receptor agonist that is currently on the market as a treatment for Type 2 diabetes also showed encouraging effects. Several other clinical trials are currently ongoing in AD patients. The present review summarizes the range of neuroprotective effects that these drugs have demonstrated and emphasizes the great promise that this approach has in providing novel treatments that have protective and even restorative properties that no current drug treatment can offer.