X-linked myotubular myopathy (XLMTM) is a disease found in humans that causes severe muscle weakness and death by respiratory failure typically by the age of 2. The disease results from a single malfunctioning gene MTM1.

In this study researchers from the UW Medicine Institute for Stem Cell and Regenerative Medicine tested the effectiveness and safety of their gene therapy in dogs with a mutation in the canine version of MTM1 (cMTM1).

The scientists used a single injection that contained a viral vector carrying a replacement copy of cMTM1. The injection was administered when the dogs were 10 weeks old and showing symptoms of the disease.

The researchers then assessed the health of the dogs, as well as expression of the replacement gene. They found that the gene was expressed in all the dogs’ muscle tissue and that the dogs showed significant improvement. After one year the treated dogs were indistinguishable from normal dogs.

“This regenerative technology allowed dogs that otherwise would have perished to complete restoration of normal health,” said Dr. Martin K. “Casey” Childers, UW Medicine researcher and physician. Childers is a professor of rehabilitation medicine at the University of Washington School of Medicine and co-director of the Institute for Stem Cell and Regenerative Medicine.


What does this mean for future gene therapy?

Well this is a great result for the viral vector they used. Traditionally there have been four key problems in attempting gene therapy:

  1. Expression: The gene has to be expressed in all the affected tissue and not expressed in other tissues.
  2. Stability: The gene has to remain stable in the affected tissue for a long period of time.
  3. Cancer: The insertion of the gene must not damage the patient’s DNA as this could lead to cancer.
  4. Immune response: The immune response to viral and plasmid vectors must not significantly reduce their effectiveness.

The vector used in this study was called an adeno-associated virus (AAV). These are a type of virus that infect human cells without causing any disease and causing only a limited immune response. The viruses are able to infect all types of cells and can remain in the cells for the life span of the cell. Crucially, this viral vector has been modified so that it does not insert itself into the genome which means that the risk of cancer from the treatment is very low. It is worth bearing in mind that muscle cells have some advantages for gene therapy as they are long lived and have multiple nuclei which likely also contributed to the success of this treatment.

AAVs show a lot of promise as vectors and have currently been used in 173 clinical trials with promising results for a number of diseases.

This study demonstrates the effectiveness of using AAV gene therapy as a treatment for human X-linked myotubular myopathy which may now go on to clinical trial.