Amyotrophic lateral sclerosis, also known as motor neurone disorder, gradually kills nerve cells in the brain, spinal cord and brain, causing paralysis, and eventually death.There is currently no cure, but we may be closer to one.Scientists were able to reverse ALS-related biological abnormalities in cells through a new study. This has been possible only for one type of the disease. It was done in laboratory samples and not in real human beings.Despite these caveats, however, this is a significant step in understanding how to treat the neurodegeneration seen with ALS patients and offers new hope that motor neurone diseases can be cured.Jasmine Harley, a neuroscientist at the Francis Crick Institute in London, says that "demonstrating proof of concept for how a chemical could reverse one of the key hallmarks ALS is incredibly exciting.""We demonstrated that this works on three key RNA binding protein, which is important because it suggests it could also work on other disease types."Most people with ALS have RNA binding proteins that help regulate RNA. They get stuck in the wrong spot. They are able to find their way out from the motor neuron nucleus, where they belong, and into the surrounding cells where they don't belong.This was reversed in human cells taken from patients suffering from ALS by the team. The team blocked VCP, an enzyme that is thought to be involved in motor neuron disease. This suggests that this enzyme may be becoming overactive and mutated in some cases.The distribution of RNA binding protein between the nucleus (cytoplasm) and the nucleus was normalized after the enzyme was removed.It is encouraging to note that the drug being used as an inhibit is also being evaluated in phase II cancer trials. This could speed up its development and availability, if it is found that the same treatment can be used for amyotrophiclateral sclerosis.The team also discovered new information about ALS in a second study by the same researchers. The researchers discovered over 100 types RNA fragments called intron-retaining transcripts that can move from the cell nucleus into the cytoplasm in ALS cases.(Giulia Tyzack)Above: Intron retaining transcripts in green might be carrying RNA binding protein (blue), to the cytoplasm in cells with ALS.Researchers found that these introns had sequences that could bind to RNA binding proteins. This was not only unexpected. These sequences, the team believes, are what draws RNA binding proteins into the cytoplasm. However, more research will be needed to confirm this.Jacob Neeves, neuroscientist, says that it is possible to imagine what's happening here by watching a movie at a cinema."We don't usually expect to see ads throughout the film. But, if things go wrong, these ads may start popping up at unexpected and unusual times. These "retained introns" are somewhat like the unusual ad breaks.About 10% of ALS cases are family-related, with only 1-2% of them having the mutated VCP protein. This is a very small target and it's not known if this technique will be effective in real patients.Both studies provide new hope that we may be able to reverse some of the damage it does to the brain and nervous systems by learning more about motor neurone diseases.Although ALS is rare, it affects approximately 2-3 people per 100,000 people in Europe every year. However, the effects can be severe and scientists don't know how it started. Although these new studies will help us to understand more, there is still much work to do.Harley says that more research is necessary to explore this further. "We must determine if this could reverse other pathological features of ALS as well as other ALS models."Brain Communications and Brain published the research.
