- Tools to identify different cells in the body rely on proteins on the surface of these cells and can be quite expensive.
- An international team of researchers supported by the International Progressive MS Alliance have developed a cutting-edge tool to identify a rare subtype of cell in the brain potentially involved in MS.
- The researchers identified two molecules as candidate therapeutic targets for reducing disease activity, particularly in progressive MS.
How can we identify different types of cells?
The human body is made up of many different types of cells. The exact number of types is unknown, and more and more subtypes of cells are being discovered as technology improves.
There are many techniques to identify different types of cells, including cells of the immune system. Flow cytometry and mass spectrometry techniques have helped us understand cells further, and have vastly improved our knowledge of some of the cells involved in MS.
These techniques rely on proteins on the surface of the cell to distinguish them from other cells, allowing isolation, identification and characterisation of the cell. They are also incredibly expensive.
Previous research suggests that a subset of star-shaped cells in the brain, called astrocytes, are involved in MS. However, these cells have few surface protein markers, making it difficult to identify and characterise them. This is also amplified by the rarity of astrocytes involved in diseases such as MS.
However, an international group of researchers have overcome this hurdle.
What did the researchers do?
In research supported by the International Progressive MS Alliance, an international group of researchers led by Dr Francisco Quintana, have developed a cutting-edge tool to identify and characterise a rare type of astrocyte. The study was recently published in the prestigious journal, Nature.
The technique involves capturing the cells into droplets, detecting the genetic material, and sorting the cells to identify them. They called the technique FIND-seq, which stands for Focused Interrogation of cells by Nucleic acid Detection and Sequencing. This technique is very cost-effective and eliminates the technical difficulties associated with other methods.
The subsets of astrocytes that have been implicated in MS are characterised by the activation of a protein called XBP1. Due to the modifications the genetic material of this protein undergoes, isolation of these astrocytes is not possible.
Using FIND-seq in combination with other tools, the research team was able to study these XBP1-driven astrocytes. The team found that there was a substantial increase in XBP1-driven astrocytes in the brain and that these astrocytes were associated with pro-inflammatory pathways in MS and models of MS.
The team also discovered for the first time that another biological pathway driven by two proteins, called NR3C2 and NCOR2, can reduce the activity of XBP1-driven astrocytes in MS-like disease.
NR3C2 is a nuclear receptor that responds to small molecules and is involved in regulating the immune system. Its ability to respond to small molecules makes it a prime candidate for the therapeutic control of disease-associated astrocytes.
NCOR2 reduces the expression of target genes via epigenetic mechanisms. Epigenetics refers to genetic changes that impact gene activity without changing the DNA sequence. These epigenetic mechanisms are involved in regulating inflammation in other diseases and may offer novel approaches for the therapeutic regulation of inflammation and neurodegeneration in MS.
What does this mean?
The team has developed a tool enabling the investigation of previously inaccessible cells, including rare subsets of cells, by leveraging differences in genetic material. This tool may accelerate how researchers study brain cells like astrocytes.
The team also identified two proteins as candidate therapeutic targets for reducing disease activity, particularly in progressive MS.
Further research is required to determine whether targeting these molecules safely and effectively limits disease activity and progression. Nevertheless, this is exciting progress, and this research could potentially pave the way for stopping MS in its tracks.
MS Australia is proud to be a managing member of the International Progressive MS Alliance. The Alliance has brought together MS organisations, researchers and people living with MS from around the world to address the unmet needs of people living with progressive MS.
