Financial boost for development of gene therapies for two rare muscle diseases

1 December 2021• NEWSITEM

Two projects in the field of rare muscle diseases, conducted by researchers at Leiden University Medical Centre (LUMC), have received grants from the Prinses Beatrix Spierfonds. The projects focus on two different muscle diseases, namely Duchenne muscular dystrophy and FSHD, but their goal is the same: the development of a gene therapy that can slow down or even halt disease progression.

Thanks to this financial support, LUMC researchers Manuel Gonçalves and Annemieke Aartsma-Rus can join forces in the development of gene therapy for Duchenne. This therapy will be aimed at restoring the production of the protein dystrophin. Due to a genetic error, Duchenne patients produce unreadable copies of the gene that contains the recipe for dystrophin. "As a result, patients cannot make the dystrophin protein. This leads to the loss of muscle cells, which eventually results in patients ending up in a wheelchair early on in their lives," Gonçalves says.

Slow down decline

With gene therapy, the genetic code can be made readable again. In this way, a dystrophin protein is produced that is smaller than normal but still partially effective. "The muscle tissue that is lost cannot be regained, but hopefully we can slow down further deterioration," says Aartsma-Rus.

However, the researchers still face a number of challenges. "For example, the correction must only take place at the desired location in the DNA. The current techniques are not specific enough for this. That is why we are now looking for gene therapy techniques that are even more specific", Gonçalves explains.

Taking away the signal

Whereas gene therapy in Duchenne focuses on stimulating the production of a protein, in FSHD the opposite is the case. "We have discovered that people with FSHD have a protein in their muscles that does not belong there. This is the DUX4 protein and causes weakening of the muscles", says Silvère van der Maarel, professor of Medical Epigenetics. He wants to use gene therapy to remove the signal from the DNA that causes the production of DUX4. "If we remove that, the protein is no longer made, but all the other processes continue as usual." 

Successful trick

Unfortunately, it is not feasible to change the DNA in every muscle cell and cure someone. However, because some FSHD patients have both diseased and healthy cells in their muscles, and they often have fewer symptoms and show a milder disease progression than people who have all their muscle cells affected, there is hope. Van der Maarel: "This shows that a positive effect can also be achieved if we only treat part of the cells.”

The aim of the gene therapy is to stop or even improve muscle weakening. "We know that we can successfully perform the trick in muscle cells that we get from patients. The next step is to see if it also works in the body," Van der Maarel says.

More information about this research can be found on the website of the Prinses Beatrix Spierfonds. Aartsma-Rus, Gonçalves and Van der Maarel are involved in the LUMC research themes Neuroscience, Medical Genomics and Cell, Tissue and Organ (Tx).

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