In this exciting study funded by The Cure Parkinson's Trust, Prof Tom Foltynie and colleagues published a report demonstrating how blood-based biomarkers could be used as objective measures of drug activity in the brain. The researchers analysed 'exosomes' - small brain cell-derived sacks - found in the blood samples of Parkinson's participants in the Exenatide Phase II clinical study, and found that the treatment (the diabetes drug Exenatide) had augmented insulin signalling inside the exosome - suggesting that the drug was having an effect inside the brain. If replicated, the implications of this research are potentially huge as it may provide an objective measure of 'target engagement' of drugs in the brain from a simple blood sample.

Background
Many types of cells in the body, including neurons, release small sacks, or vesicles, containing a range of different molecular messages as a means of communicating with other cells. Exosomes are one particular type of extracellular vesicle. Once released, they can cross the blood-brain barrier and travel around the body in the blood, carrying different chemical messages to other tissues. Analyzing exosomes through simple blood samples opens up the possibility of getting important insights into the molecular state and function of neurons.

Recently, the antidiabetic drug Exenatide was trialled in Parkinson’s and was shown to improve movement-related function which was sustained even after the drug had been stopped for 12 weeks. Part of the assessments in this trial included people having blood samples taken. These blood samples have since been analysed to assess changes in exosomes as a result of Exenatide. 

The details
Using different biochemical methods, exosomes which were specific to neurons were isolated from the blood samples of the original group of participants, half of whom received Exenatide and the other half received a placebo. Given that Exenatide acts on insulin pathways, the team predicted that compared to the placebo group, exosomes from patients who had received the drug should show greater increases in signalling molecules involved in insulin-related pathways, which we also know promote neuronal survival.

Exosomes from blood taken after 48 weeks of Exenatide treatment showed increases in markers of three important cellular pathways involved in insulin signalling, which correlated with the degree of symptom improvement. One of these pathways enhanced on Exenatide, called mTOR, also predicted lasting symptom improvement even after the drug was stopped.

Read the paper in full.

Read this editorial piece of the study, which raises some interesting questions for follow up research.