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Many people are familiar with RNA from the mRNA vaccines developed during the COVID-19 pandemic, but medicines specifically targeting RNA are a whole different matter. RNA medicines differ from other treatments in that they alter or eliminate RNA, which affects the cells’ functions.

Just as we have DNA in every cell of the body, we also have RNA, which takes different forms and fulfils other functions. The best known is messenger RNA (mRNA), molecules that read the gene sequence ‘recipes’ for the proteins involved in many of the cells’ processes. This function makes mRNA particularly relevant to Huntington’s disease, in which proteins play a crucial role. It is hereditary, and unless both parents have it, their children will have one healthy and one diseased copy of the gene.

It may be possible to identify the genetic defect, but so far, it has proven impossible to tell the difference between healthy and diseased mRNA. Supported by the Lundbeck Foundation, Ørom has now made an important discovery. He has shown that in mice, the structure of the diseased mRNA differs from the healthy mRNA due to so-called “modifications”, i.e. chemical changes.

It is normal for mRNA to undergo thousands of modifications, but some of them in diseased mRNA are unique and expressed in a different chemical structure, making it possible to identify the diseased mRNA and target it with medication.

’mRNA usually has a good, well-defined structure, which folds a certain way. But modifications to the diseased mRNA change that structure and make it more unstable, which has an impact on its function. In the case of Huntington’s, this can lead to protein aggregation in the cells.’

Ørom has also identified certain molecules that can attach to the specific structure of the diseased mRNA. If these molecules can also neutralise or break down mRNA, it may be possible to curb the production of the pathogenic protein in people with Huntington’s disease. It also means that it may be possible to do so without damaging the cell itself or the healthy mRNA. Selectively removing the pathogenic mRNA is a brand-new approach. In previous trials with patients, other researchers have eliminated both the healthy and diseased mRNA.

’Afterwards, the patients did not feel well, so the healthy mRNA has to be there. The challenge lies in removing only the diseased mRNA,’ he explains.