Exploring new tools to correct gene changes in muscle wasting conditions

Genes are like instruction books that tell our cells how to make proteins. Proteins do important jobs to keep our cells and muscles healthy. But if there’s a change in a gene, the protein might not be made properly or not made at all. This can lead to muscle damage.

Genes are made up of letters, like a sentence. The order of the letters matters. A small change — like swapping one letter for another — can completely change the meaning. For example, the sentence “Greg got a great gift” becomes “Area aot a areat aift” if you change every ‘G’ to an ‘A’. It doesn’t make sense anymore, and the cell can’t make the protein properly.

This kind of letter swap (from G to A) can be found in Duchenne muscular dystrophy (DMD) and collagen VI-related muscular dystrophy.

Scientists are now testing ways to correct these changes using a technique called RNA editing. RNA is a copy of the gene that the cell uses to make proteins. RNA editing fixes the mistake in the copy — like correcting a typo in a printed page rather than rewriting the whole book.

The team is testing two ways to change the letter A back to G in the RNA instructions. This could help the cell make the protein the way it should, which may reduce muscle damage. They will start by testing them in DMD and later try them in collagen VI-related muscular dystrophy.

The two methods are:

1) Using a harmless virus to carry an RNA editing tool into cells. This tool changes the A back to a G in the RNA.
2) Using a short piece of RNA to guide the cell’s own editing tools (called ADAR) to the mistake. ADAR changes A to I, which the cell reads as G.

Both methods will be tested in muscle cells grown in the lab and in animals with the same gene change. These are called models and help scientists see how the treatments might work.

Some treatments for DMD are being developed, but they only work for certain gene changes. This means they might not help everyone. For collagen VI-related muscular dystrophy, there are no treatments available yet. This research explores a new way to correct one type of gene change, which could lead to treatments for more people — including those with DMD, collagen VI-related muscular dystrophy, and possibly other muscle wasting conditions. It’s still early-stage, but if successful, it could lead to clinical trials in the future.