Suggesting a Way to Understand the Actual Potential of Anti-Alzheimer’s Disease Drugs That Show Promise in Transgenic Mouse Models

One conundrum in Alzheimer’s disease (AD) research using transgenic mouse models is the high amount of successful memory-enhancing drugs. By contrast, very few drugs and of limited efficacy are available for humans having this pathology. As previously discussed (1), the advance in this field, i.e., to fulfill the translational facet of anti-AD research, requires deciphering why so many different drugs (or therapeutic interventions, such as exercise or training) havememory-enhancing properties in transgenic models of the disease. Transgenic animals do not accurately reflect the human disease, as they overexpress proteins with mutations that appear only in a reduced percentage of patients (2). The majority of patients have late-onset clinical symptoms due to multiple factors many of which may be circumstantial. On waiting for the development of novel animals models that may, eventually, shorten the distance between the lab bench and the bedside (3), we should take advantage of the huge amount of data showing promise of different drugs in transgenic models. A way to do it is by designing medium-to-high throughput experiments to compare anti-AD effects of closely related drugs. In this commentary, we focus on small drugs with the same chemical formula, but with different 3-D structure. A significant number of drugs approved for human consumption for fairly different illnesses have a special structural characteristic called stereoisomerism (see Figure 1). Examples of small molecules with alternative stereoisomer variants (enantiomers) that are alreadymarketed for human consumption include verapamil, ibuprofen, citalopram, and thalidomide. Due to the difficulties in isolating the two enantiomer species and other operational reasons, mixtures of the two species are approved for human consumption.