MDUK-funded research has shown that a new type of molecular patch was beneficial in a mouse model of DM1. Although more research is required before we could see these patches in the clinic, these results are a positive step towards developing a potential treatment.
Myotonic dystrophy type 1 (DM1), one of the most common muscular dystrophies, is caused by a change (mutation) in the DMPK gene. The change causes the DMPK RNA to take on an unusual shape, trapping it in the nucleus. This causes toxic effects within the cell, including splicing defects that disrupt other genes and proteins.
Molecular patches are short DNA-like molecules that can change how a gene is read. They are currently being investigated as potential treatments for several muscle-wasting conditions. Spinraza, the first treatment for spinal muscular atrophy, is a type of molecular patch.
In the case of DM1, molecular patches have been designed to bind the damaging DMPK RNA and break it down. It’s hoped that this sort of genetic treatment could reverse or slow down the deterioration of tissues affected by DM1.
Molecular patches aren’t very good at getting into cells within the body, which limits how effective they can be. Professor Matthew Wood from the MDUK Oxford Neuromuscular Centre has developed a new type of molecular patch linked to protein fragments called peptides. These peptide-linked molecular patches have been shown to pass into cells more easily.
In this new study, Professor Wood and others tested several peptide-linked molecular patches in mouse models of DM1 and muscle cells taken from people with DM1. They wanted to find the most effective patch that had the least amount of side effects.
The researchers found that the peptide-linked molecular patches were able to penetrate cells more efficiently, which improved their delivery to muscles. They also found that the molecular patches got into the heart and diaphragm of the treated mice. The patches successfully corrected splicing defects, which reduced myotonia in the mice.
The positive results from this study support further research in this area, with the hope that we can eventually use molecular patches to correct the genetic cause of DM1.
However, though exciting, it is important to remember these peptide-linked molecular patches have not yet been tested in humans with DM1. This means that their effectiveness is currently unknown and more research, including several clinical trials, will be required to show that they are a safe and an effective treatment for DM1.
Molecular patches have the potential to treat the underlying genetic causes of a range of muscle-wasting conditions. This study has helped us to understand how we can improve their efficiency, which will be helpful when researchers are designing molecular patches for other neuromuscular conditions.
Read the full scientific paper here.
Find out about other myotonic dystrophy projects that we are funding here.