Researchers from Tokyo Medical and Dental University have now found that the problems linked to using antisense oligonucleotides to treat brain diseases are caused by imbalances in calcium levels.
Scientists have come up with a possible solution to treating certain diseases affecting the brain. They use special molecules called antisense oligonucleotides (ASOs). These molecules help to control how RNA and proteins are made in your body. However, injections containing these drugs can cause side effects.
Scientists from Japan have recently published a study in the journal Molecular Therapy- Nucleic Acids and found that problems caused by taking antisense oligonucleotide therapy could be corrected by using special substances called modulators. These help to control the levels of calcium in the brain, which can stop these side effects.
Many diseases that target the brain can be caused by certain proteins. A special type of medicine called ASOs, can be created to attach onto the specific RNA strands that is behind the protein production. For safety, these medicines are injected directly into the cerebrospinal fluid – a liquid that passes through and around our brain and spine. Unfortunately, only one form of this medicine exists so far and it’s used to treat spinal muscular atrophy.
The scientists from Tokyo Medical and Dental University are focused on finding ways to help people who feel really bad sideeffects known as neurotoxicity after taking something called an ‘ASO’. Neurotoxicity is a disturbance in our consciousness or movements that can be dangerous. Because of this, it’s very hard for experts to make new ASOs which won’t cause neurotoxicity or treat already-existing ones. The team from TMDU hopes to find solutions!
The lead researcher, Chunyan Jia, explained that the team injected three special substances called ASOs into mice. The injection caused strange behaviors in the mice which suggested that their brains had been affected and this reaction was linked to changes in the level of calcium inside brain cells.
Using special treatments, researchers found out that they can reduce the amount of calcium inside cells. This change caused a reduction in toxicity levels among mice. Basically, this research suggests that calcium levels inside cells play an important role in controlling how toxic an treatment is and how to adjust it to reduce its toxicity levels.
Kotaro Yoshioka, the senior author, said our findings can help make ASO (Antisense Oligonucleotides) therapies stronger while also having less bad side effects. Takanori Yokota, director of the research group, noted that there are certain sequences in ASOs that may be linked to more neurotoxicity symptoms. He also argued that this information could be used to choose potential ASOs for clinical use.
Scientists are trying to find new ways to help treat and cure serious brain diseases that don’t have an actual cure right now. This study will help them make better treatments with fewer side-effects and can even improve the way they create these treatments for really rare diseases.
A group of scientists have found that changes in the calcium levels inside patients’ cells can make their brains become toxic, which is why they are using a type of medicine called “antisense oligonucleotides” to try and fix it. They gave this medicine to people through their spinal fluid and published the results in Molecular Therapy – Nucleic Acids on December 23 2022.
This study was sponsored by several organizations in Japan, including the Japan Agency for Medical Research and Development, the Japan Science and Technology Agency, and the Japan Society for the Promotion of Science.
