New Approach Cures some RNA toxicity in Fly’s and Mice with Myotonic Dystrophy

Another strategy for a cure of for myotonic dystrophy treatment

Researchers at the University of Valencia in Spain led by Amparo Garcia-Lopez recently identified a new way to block the genetic change that causes myotonic dystrophy type 1. They used a fruit fly model to screen for potential drugs and then tested the most promising one in mice. The muscles of the treated mice appeared healthier under the microscope. This new research is encouraging and if replicated in humans it would be expected to be an effective treatment.

Read the full study PDF here ==> Reverses RNA toxicity Study Spain


Myotonic dystrophy is caused by the inheritance of extra pieces of DNA code. In myotonic dystrophy type 1 (DM1), the most common type of myotonic dystrophy, a three letter DNA code is repeated many hundreds of times instead of the usual number which is less than thirty.

It is known that RNA – the carbon copy of DNA that carries genetic messages from the center of the cell (the nucleus) to the rest of the cell in order to build proteins – is key to causing myotonic dystrophy.

The characteristic clumps of RNA and protein (pink) stuck inside the nucleus (blue) of muscle cells
The characteristic clumps of RNA and protein (pink) stuck inside the nucleus (blue) of muscle cells. These are called Foci by the scientists and researchers. They basicly clog the cells and do not allow certain critical elements to leave the cell.

The extra DNA repeats cause the RNA copy of the DNA to fold in half into a hairpin shape. This gets stuck inside the nucleus and hooks onto certain proteins trapping them inside the nucleus. This leads to the formation of clumps of RNA and protein in the cell nucleus. The proteins held in these clumps are then unable to perform their normal functions elsewhere in the cell.

In this new research they searched for a substance that could block this chain of events that leads to the symptoms of myotonic dystrophy.

What did this research show?

The researchers in Spain used a fruit fly model of DM1 to screen millions of small pieces of protein which are called “peptides” for any that could be effective for myotonic dystrophy.

Although fruit flies might seem like an unusual model to use when looking for a treatment for a human disease, they are a relatively fast and cheap way to screen for potential drugs that can then be tested in larger animals and eventually in humans.

The flies they used have a genetic change similar to people with myotonic dystrophy. These flies don’t live past the pupal stage (a little maggot-like larvae in a cocoon). So if the peptide didn’t work, the researchers didn’t see any adult flies emerge from the cocoons. If it did, flies flew out of the cocoons. The life cycle of fruit flies is very short so it was soon obvious if the peptide drug was having an effect.

The researchers then narrowed the promising peptides down to one and tested it in a mouse model. They injected it into mice with myotonic dystrophy then looked at their muscles under a microscope. The treated mice had muscles that looked healthier. This peptide seemed to work by stopping the RNA forming a hairpin shape and it then was unable to trap important proteins. Consequently, the researchers were able to show that in the treated mice these proteins were able to resume their normal functions within the muscle cells.

What does this mean for You or your patients?

Ever since scientists started to understand how the DNA change in people with myotonic dystrophy was exerting its effect in the late 1990s, they have been searching for potential treatments that specifically target the harmful RNA. In the 2000’s the research centered on Foci or areas in the individual cells that seemed to get clogged. These Foci are the target of many of the therapies. There are several different approaches being developed in laboratories around the world. This new research is important because it brings forward a new strategy to target the harmful RNA which has the potential to go forward to clinical trial. The more promising ways we have of tackling the condition the more likely one will be successful in the end.

A major hurdle for any therapy for myotonic dystrophy will be to deliver the drug as widely throughout the body as possible. This is because people with myotonic dystrophy often experience,in addition to muscle weakness and stiffness, symptoms in many other parts of the body such as heart problems, cataracts in the eyes, daytime sleepiness, diabetes and infertility.

Another strategy that is being explored for myotonic dystrophy is the use of small pieces of DNA called antisense  that could block the repetitive RNA. This approach led to a major breakthrough in 2009 when researchers in the US lead by Prof. Charles Thornton showed that AOs were able to reverse some of the symptoms of myotonic dystrophy in a mouse model of myotonic dystrophy. Isis Pharmaceuticals has partnered with Biogen and are spending over $100 million to bring this technology to market although it is a few years away

We don’t know yet what approach is most likely to result in an effective, safe treatment, but it is promising that several lines of attack are coming forward. Researchers in Both the USa and Europe are activitly working on cures for this disease. Isis, Prosena, and others are leading the way for a cure to come

Prof. Darren Monckton, myotonic dystrophy researcher at the University of Glasgow said:

The data are certainly very encouraging and if replicated in humans would be expected to be therapeutically beneficial. The next step will be to show that such a peptide could be delivered effectively at the dose required in humans. At the very least though, the study provides important biological information and a solid lead for drug development. As such it is an exciting development as we have so few real leads in this disorder.


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