Multiple Sclerosis (MS) is a debilitating disease where the immune system mistakenly attacks myelin, the sheaths protecting neurons in the nervous system. Like exposed electrical wires, this effectively short-circuits the nerves, disrupting communication between the brain and the body that leads to impaired motor skills and cognition. Now, researchers at Melbourne University have developed a synthetic peptide that helps regenerate myelin, potentially slowing the progression of the disease.
MS is a complicated disease, but on the plus side that means there are several targets for potential treatment. One is to stop the immune system overreacting to myelin, which has been attempted in past studies by destroying "rogue" B cells, conditioning the body to better tolerate myelin, or even "rebooting" the whole immune system. On the other hand, progression can be slowed or reversed by finding ways to restore damaged myelin through drugs, stem cells and gene therapy.
The Melbourne University study falls into the latter camp. The researchers focused on a growth factor called Brain-Derived Neurotrophic Factor (BDNF), which helps to grow and replenish brain cells and myelin. This factor has been studied in the past for its MS treatment potential, but it's proven difficult to work with. That's because BDNF has a relatively large molecular size, it interacts with several receptors and it quickly breaks down in the body.
To overcome those problems, the team developed a synthetic peptide called TDP6, which acts as a smaller, more directed version of the natural growth factor. The researchers singled out a receptor called TrkB, which is expressed by myelin-producing cells and responds to BDNF. They designed the synthetic peptide to only recognize this receptor, which makes the peptide smaller, more stable and more selective than BDNF.
In mouse tests, the team found that TDP6 boosted myelin regeneration much better than BDNF, by increasing the number of cells that produce the protective material. The newly formed myelin layers were also thicker than restored myelin usually is, and intact TDP6 was detected in the mice after seven days, which is far longer than BDNF lasts. To confirm that the TrkB pathway was involved, the researchers also engineered mice without it, and found that TDP6 no longer worked.
"There's nothing currently available to help with myelin sheath repair," says Jessica Fletcher, lead researcher on the study. "The beauty of what our team has done is taken what naturally occurs in healthy cells and used that to manipulate a similar response in damaged cells. It's very basic foundation research to show that this idea can work."
As the researchers point out, the work is in the very early stages, but the results so far are promising. The team says the next steps will be to further study how the synthetic peptide works to restore myelin, and to develop new and improved versions of TDP6.
The research was published in the Journal of Neuroscience.
