Ask A Scientist – Get answers straight from the experts

The experts at the Kids Neuroscience Centre, part of the Sydney Children’s Hospital Network, are giving the neuromuscular community the chance to submit their medical questions directly to their team of scientists! Just email us at and we’ll pass your question on and within weeks you’ll have an answer! Here’s a question from MDNSW member, Dorothy about Myotonic Dystrophy.

Question: “Are there any Gene therapies for Myotonic Dystrophy yet?” 


It has taken more than twenty years from discovering that myotonic dystrophy is caused by an expansion in the number of CUG repeats in the the DMPK gene, to now having several promising avenues for therapies (for recent reviews see (1, 2)).

The mechanism of disease in myotonic dystrophy is complicated: The CUG repeating units in the tail of the DMPK messenger RNA (mRNA) acts like sticky fly paper that collects lots of RNA-binding proteins.  This;

1) sequesters RNA binding proteins that are now unable to bind to other RNAs they should be binding to,

2) creates sticky clumps of RNA and protein that clog cell machinery and act as roadblocks in RNA transport routes, and

3) ultimately prevents the DMPK gene from making myotonic dystrophy protein kinase protein which muscle cells need to be healthy.

Mopping up RNA binding proteins and creating road-blocks in RNA transport pathways helps to explain why DMPK expansions can have a knock-on toxic effect for lots of different mRNAs. Expansions of different sizes or nature can have different levels of toxicity, in turn explaining why disease severity and involvement of other organs in addition to skeletal muscle can be variable in myotonic dystrophy. This article from the MDA helps to explain disease mechanism in myotonic dystrophy:

There have been some promising results with therapies based on antisense oligonucleotides (ASOs) in myotonic dystrophy, as well as in other disorders like spinal muscular atrophy and
Duchenne muscular dystrophy. Challenges with delivery of ASOs into the skeletal muscle to treat myotonic dystrophy are being addressed by packing the ASOs into lipid vesicles (for
example, (3)), or by connecting the ASO to another molecule; for example, a lipid (4) or peptide (5) that improves stability of the ASO in the bloodstream and/or helps it cross from the blood supply and into the muscle cells. The muscular dystrophy news provides a recent commentary on one study –

Another study published in 2021 have used a neat CRISPR/Cas9 approach to silence toxic DMPK messenger RNAs.  Batra et al.,(6) used an adeno-associated virus (AAV) to deliver an inactive form of the Cas9 enzyme that specifically targets and binds to messenger RNA’s with CUG expansions and essentially “removes them from the system” – stopping the cascade of toxic effects. Injections of the AAV directly into muscle, or into the bloodstream, got into skeletal muscles and other tissues of injected mice.  Importantly, AAV injections in a mouse model of myotonic dystrophy resulted in sustained reversal of some of the key phenotypes for up to 3 months after injection.

Though it is early days on the therapeutic journey toward new CRISPR/Cas9 trials in individuals affected with myotonic dystrophy, important research progress is being made.  For further information, we recommend you check out the Myotonic Dystrophy Foundation’s page on this topic:

Thank you!


  1. Gourdon G, Meola G. Myotonic Dystrophies: State of the Art of New Therapeutic Developments for the CNS. Front Cell Neurosci. 2017;11:101.
  2. Overby SJ, Cerro-Herreros E, Llamusi B, Artero R. RNA-mediated therapies in myotonic dystrophy. Drug Discov Today. 2018;23(12):2013-22.
  3. Jauvin D, Chretien J, Pandey SK, Martineau L, Revillod L, Bassez G, et al. Targeting DMPK with Antisense Oligonucleotide Improves Muscle Strength in Myotonic Dystrophy Type 1 Mice. Mol Ther Nucleic Acids. 2017;7:465-74.
  4. Yadava RS, Mandal M, Giese JM, Rigo F, Bennett CF, Mahadevan MS. Modeling muscle regeneration in RNA toxicity mice. Hum Mol Genet. 2021;30(12):1111-30.
  5. Klein AF, Varela MA, Arandel L, Holland A, Naouar N, Arzumanov A, et al. Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-derived cells and mice. J Clin Invest. 2019;129(11):4739-44.
  6. Batra R, Nelles DA, Roth DM, Krach F, Nutter CA, Tadokoro T, et al. The sustained expression of Cas9 targeting toxic RNAs reverses disease phenotypes in mouse models of myotonic dystrophy type 1. Nat Biomed Eng. 2021;5(2):157-68.