Experimental drug for muscle disease DM1 repairs a large share of RNA errors in small study

Myotonic dystrophy type 1, or DM1 for short, is an inherited muscle disease. Muscles become weaker and have trouble relaxing: someone who squeezes their hand into a fist can only open it again slowly. The disease can also affect the heart and other organs. There is not yet a treatment that tackles the cause.

On 10 November 2026, the US biotech company PepGen announced the first results of a drug that aims to do exactly that: PGN-EDODM1. In a small study, it repaired a large part of what goes wrong in the disease in the muscles of six treated participants, and they also improved in strength and movement.

What goes wrong in DM1

Cells make proteins using a working copy of the DNA, called RNA. Before such a copy is used, the cell cuts pieces out of it and joins the rest together. This is called splicing. In DM1, the working copy of one gene contains a repeat of the same three letters that is far too long. These long strands fold into loops and trap a protein, MBNL1, that the cell needs to cut and join correctly. As a result, the splicing of many other genes goes wrong, and the muscles work less well.

PGN-EDODM1 is a short, artificial piece of genetic material that fits exactly onto that repeat. It attaches to it, so that MBNL1 is released again. To get the drug into the muscle cells and all the way into the cell nucleus, PepGen has linked it to a small protein particle that passes easily through the wall of a cell.

The results

In the phase 2 study FREEDOM2-DM1, eight adults received four infusions, one every four weeks. Six received the drug at a dose of 10 milligrams per kilogram of body weight, and two received a placebo. Nobody knew who received what. After thirteen weeks, the researchers took a small sample of muscle tissue and looked at 22 genes whose splicing goes wrong in DM1. On average, 46.5 per cent of those errors had been repaired. In five of the six treated participants this was more than 20 per cent, and in four it was more than half. According to PepGen, this is the largest repair ever reported in a DM1 study with multiple doses.

The muscles also worked better. After sixteen weeks, the treated participants needed on average 3.9 seconds less to open their clenched hand, about 53 per cent less than at the start. Their grip strength increased by around 16 per cent. In the placebo group, the hand test hardly changed. Questionnaires in which participants reported how they were doing did not yet give a clear picture.

The drug was well tolerated: all side effects were mild or moderate, and nobody stopped the treatment. Nausea was the most common. There were four mild side effects affecting the kidneys, such as some protein in the urine after the first dose, which decreased with the following doses.

Next steps

The group is small, and the placebo comparison for splicing comes from earlier groups in the same study. Larger studies need to show whether the effect holds. For now, no participants can take part in the United States: the US Food and Drug Administration (FDA) paused that part of the study in March 2026 because it had questions about earlier animal research. The treatments took place in Canada, the United Kingdom, New Zealand, Australia and South Korea. PepGen expects new data from a follow-up study in January 2027 and results from a group with a higher dose in the first half of 2027.

What does this mean for the road to the singularity?

The biggest challenge with this kind of drug is getting it into the muscle cells. This small study shows that PepGen's approach can do this, and that repairing the splicing goes hand in hand with better-working muscles. If larger studies confirm this, a first treatment for the cause of DM1 comes into view. A reliable way to deliver such drugs into muscles is also an important building block for other inherited muscle diseases.

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