Genetic engineering for neuroprotection?
Original article: Neuroprotective effects of an engineered commensal bacterium in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine Parkinson disease mouse model via producing glucagon-like peptide-1, Journal of Neurochemistry: March 9, 2019.
Researchers have created a strain of bacterium that constantly produces Glucagon-like peptide 1 (GLP1), the hormone whose action is enhanced by the diabetes drug exenatide, which has been shown to have beneficial effects in models of Parkinson’s. Mice that had been orally given these bacteria were less vulnerable to the effects of toxins normally used to simulate Parkinson’s
Why is it important?
This work opens up new possibilities into more continuous GLP1 targeting for neuroprotection in Parkinson’s.
- Novelty 85% 85%
- Proximity 60% 60%
- Deliverability 50% 50%
“It is now recognised that the bacteria of our gut can have a major impact on our health and well being. There is even research suggesting that these microbes may be influencing the course of Parkinson’s. It is therefore interesting that the genetic manipulation of bacteria in the gut is being proposed as a therapeutic approach for Parkinson’s. Currently, GLP-1 based treatments require weekly injections, and as many people do not like needles, a more continuous method of treatment delivery – via engineered bacteria in the gut – could be easier for people to stomach.”
GLP1 is released naturally in the gut and helps with the control of blood sugar by enhancing the effects of insulin, the hormone which helps ferry glucose into cells. A recent clinical trial of exenatide, a drug which promotes the action of GLP1, in people with Parkinson’s has shown promising results and a Phase III clinical trial of exenatide is now in development.
To get around the problems associated with administering drugs that enhance GLP1, one of which is their short lived effects, researchers in China genetically engineered a strain of bacterium to continuously produce GLP1. The group had observed that giving these bacteria to mice had neuroprotective effects in a mouse model of Alzheimer’s. They then addressed the effects of these bacteria in a mouse model of Parkinson’s.
The researchers compared 6 groups of mice, which were either treated with the toxin used to create the mouse model of Parkinson’s, or an injection of salt water alone (as a control), or different combinations of the toxin and the bacteria, which were given before, at the same time or after the toxin.
They observed that the animals that had been pretreated with the bacteria performed better on tests of movement. They found a number of positive results, including reduced brain inflammation and a greater number of surviving neurons. Interestingly, animals that had received the GLP1 genetically engineered bacteria had lower levels of a gut microbe which previous studies have shown may be increased in people with Parkinson’s. In addition, they had higher levels of two different probiotics, that is, resident gut bacteria.
The mechanism underlying these findings is not clear: they could be due to effects through GLP1 or some other unknown mechanism triggered by this bacterial strain. Future experiments will have to validate the underlying mechanism before addressing the potential of this genetically engineered bacterium as a disease modifying therapy.
Original article: Neuroprotective effects of an engineered commensal bacterium in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine Parkinson disease mouse model via producing glucagon-like peptide-1, Journal of Neurochemistry: March 9, 2019. Fang X, Tian P, Zhao X, Jiang C, Chen T.