Healthcare (Commonwealth Union) – Researchers at University College London (UCL) have found that a more accurate physical model of microscopic nerve fibers called axons could speed up the development of treatments for multiple sclerosis and other brain disorders that get worse over time.
Scientists stated that the test for possible drugs on a fake structure that is very similar to the physical properties of human axons give it a shorter chance for the drugs to work well in lab experiments but not seen for human clinical trials.
The immune system mistakenly attacks myelin, which is the protective coating around axons, in people with multiple sclerosis (MS). The new model saw the replication of these long nerve fibers, which have the responsibility of transmitting electrical signals via the brain and spinal cord.
Detailed in a paper published in Nature Methods, the model is built from microscopic pillars that are tens of times thinner than a human hair and designed to imitate axons. Unlike earlier versions made from rigid materials like plastic, the new system uses a water-rich gel, or hydrogel, whose softness can be tuned to closely match that of real axons.
The researchers cultivated myelin—using both human and animal cells—around the tiny pillar structures and introduced drugs that have been suggested as possible treatments for repairing or restoring damaged myelin. This let them see if the drugs helped myelin grow.
The findings indicated that the drugs exhibited diminished efficacy when the artificial axons were engineered to closely mimic natural axons, especially when their pliability corresponded to that of authentic nerve fibers. This could help explain why some drugs that looked promising in the lab didn’t work in people.
The work also marks the first time that scientists have been able to grow myelin from human cells in a lab setting.
Professor Emad Moeendarbary, the senior author from UCL Mechanical Engineering, said that therapies that can fix myelin are necessary to stop multiple sclerosis. He said that a number of drug candidates that seemed promising at first ended up failing in clinical trials with real people. He said that one possible reason is that many lab models don’t accurately show the basic physical features of the human brain.
In addition, animal brains differ from human brains in areas known as white matter, which contain dense bundles of myelinated axons.
“Our work suggests that commonly used rigid models, hundreds of times stiffer than real axons, can generate misleading drug hits. We believe that our more life-like model can be used as a more robust early test of drug candidates and as a platform to discover new drugs.”
The brain’s reduced ability to safeguard nerve fibres by repairing and rebuilding myelin plays a major role in neurodegenerative illnesses such as Multiple Sclerosis, Alzheimer’s disease, Parkinson’s disease and Motor Neurone Disease.
Myelin is normally restored or replaced by specialised brain cells known as oligodendrocytes. In the early stages of MS this repair process can still function, but as people age and the immune system repeatedly attacks the myelin, the repair mechanism gradually becomes less effective.
The axons that myelin protects transmit signals responsible for nearly everything the body does — including movement, thinking and emotions. When myelin is damaged, these signals can slow down or fail to reach their destination, and in severe situations the exposed neurons may eventually die.
Scientists made artificial axons called micropillars for the study. They made the tiny molds using a micro-fabrication technique called photolithography. Then, they filled the molds with hydrogel to make the pillar-like structures.
Professor Moeendarbary, an expert in cellular mechanics, said that hydrogel is very similar to living cells. It is mostly made of water and has a porous structure, just like real cells. But making a soft hydrogel on such a small scale is not easy.
