Gene therapy

What is gene therapy in general?

A very good overview you can find on this page [] (from where also the pictures in the right is taken from). In general, a virus is used to transport a certain gene into the cells which need this gene.



Gene therapy for Myotubular Myopathy

Recent Information suggests that the company Audentes Therapeutics will start with a clinical trial für gene therapy for MTM1  in the year 2017 (myotubular myopathy). The product of the company is called “AT132”

What gene is replaced?

That is the gene, that is not working in people with myotubular myopathy.

What is AT 132?

AT132 consists of a  virus (AAV), in which the MTM1 -gene and  a promotor have been placed

What is a promotor and for what is it needed?

A promotor is a short gene sequence which clarifies in which cells the following gene should be read. (Otherwise, without promotors in muscle cells genes for hairs or eyes would be read too). Thus, each “muscle-gene” has a preceding promotor that says “read in muscle cells!”.

MTM1-gene and promotor can be built into a virus.

What kind of virus is this?

The virus belongs  to the class of the AAV – adeno-associated viruses. This virus looks like a sphere with a hole. Inside would be the genetic information of the virus. As soon as it infects a human it will built in  this genetic information into the nuclei of human cells. This information is the read (instead of the own genetic information). Thus, the virus re-programs the cells – and it lets produce copies of itself. This is what you deal with if you have a viral infection.

And how these three parts form AT132?

Audentes is now doing the following: The genetic information of the virus is removed. Now it is an empty sphere. Then, the MTM1-gene and the promotor are put into this sphere. This is AT132.

Fortunately, the MTM1-gene is quite small. For this reason it fits together with its promotor in the empty virus sphere. Unfortunately, most of the genes are far to long to be built into viruses. Therefore, up to now MTM1 is the only gene where gene therapy could work.

How does gene therapy work?

If you inject million of these viruses into dogs affected with myotubular myoptahy then it is healed.

The  virus finds “knows” the way to the muscle cells (usually it would cause a muscle inflammation). However, in our case it transports the MTM1-gene and promotor into the muscle cells. An “infected cell produces then myotubularin. This is the enzyme that lacks the people with myotubular myopathy.

There is an impressive video of the Myotubular Trust that shows the healing in dogs.

Is this medicine for gene therapy available?


Before, AT132 has to be tested in a clinical study. When the efficacy of AT132 has been proved, negotiations between pharmaceutical company and health insurances (aka health technology assessment (HTA) bodies) on the price of begin. This is the last step before patients get access to the medicine.

What has been already achieved?

The company Audentes Therapeutics has conducted a literature study called RECENSUS, which uses literature data to describe the course of myotubular myopathy or summarize the condition of those affected. The results of the study were published on 20 March 2017. Click here for the poster and press release.

The second step is a study of the natural course of the disease (“Natural History Study”). This study currently runs in the USA, UK (London) and Germany (Munich). Audentes has named this study INCEPTUS.

Audentes has applied to the supervisory authorities, the EMA (European Medicine Agency) in the EU, and the FDA (Food and Drug Authority) in the US to begin the clinical trial [named ASPIRO by Audentes]. For this, EMA and FDA require slightly different preclinical studies from Audentes.

What are the next steps?

On 3 April 2017, the FDA issued this permission for clinical trials, a so-called IND. Audentes has published a press release. IND stands for Investigational New Drug. This IND now paves the way for the clinical study of gene therapy in the US.

On 21 September 2017, Audentes Therapeutics announced that the first patient has been dosed with AT132. Thus the clinical trial (ASPIRO) has begun. Audentes Therapeutics has  published this press release.

For the EU, the equivalent to be issued by the EMA is called CTA (clinical trial authorization). It is expected that EMA will issue the CTA in the third quarter of 2017, and Audentes Therapeutics will then open study centers in the EU in the fourth quarter of 2017 or the first quarter of 2018. AT132 is expected to be tested on 12 boys with myotubular myopathy in Europe and the USA. 

On 4 January 2018, Audentes Therapeutic published first preliminary results of the first cohort of patients in ASPIRO. These results are quite promising. More information can be found here.

When AT132 will be available?

If all goes well, after the clinical trial AT132 is approved as a cure. If AT132 is approved as a remedy, pharmaceutical companies and health insurance companies still have to agree on a price. Only when these negotiations are concluded, AT132 comes onto the market.

Which other therapeutic approaches for centronuclear myopathies are in development?

There are at least three other approaches, which we have listed on this page.