Gene Therapy: Dramatically improvement on children with myotubular myopathy

The gene therapy developed for children with myotubular myopathy has had astonishing results in clinical trials. Nine children have received the treatment until now and their neuromuscular function has improved dramatically. Most children can now sit on their own, four are now breathing without ventilators and three are making stepping movements.

Myotubular Myopathy (MTM) is caused by a defect in a gene called MTM1 that encodes the enzyme myotubularin. Skeletal muscles need the enzyme to develop and function. Children with MTM have low muscle tone and most of them cannot move so much, breath or swallow on their own. This means that most children require a ventilator to support their breathing, a feeding tube and are wheelchair-dependent. Sadly, half of the patients die before their second birthday and only a few live past age 10.

ASPIRO Clinical Trial

In the ASPIRO trial, performed by the company Audentes Therapeutics, children with MTM received an intravenous (IV) infusion of a harmless virus, called an adeno-associated virus. This virus carries a healthy copy of the MTM1 gene into the children’s muscle cells. The gene reaches the cell nucleus and triggers the production of the enzyme myotubularin. Find out more about gene therapy in our website.

Until now 11 children between 8 months and 6 years have been enrolled in ASPIRO from which 9 have received the gene therapy. The two other children served as an untreated control group.

Efficacy of the treatment

The newly reported data by Audentes included efficacy assessment and safety of the patients as of April 8, 2019 cut-off date. Six patients belonging to cohort 1 have received a dosis of 1×1014 vector genomes per kilogram (vg/kg), while 3 patients in cohort 2 have received the threefold dosis as in cohort 1. The presentation of the results can be found under this link.

Muscle biopsies showed that 24 to 48 weeks after the first boys received treatment in cohort 1 their muscle fibers have grown larger and resemble the muscle fibers of healthy children. Also the production of myotubularin in the muscle cells have reached 83% of the normal amount (median). For the children in cohort 2, the improvement in the muscle cells has been more rapidly (by month 24) in comparison to the children in Cohort 1.

In addition, the majority of patients have demonstrated progressive achievement of motor developmental milestones, such as head control, sitting unassisted, crawling, standing with support and initiating stepping movements.  Four patients can now breath on their own and all patients demonstrate a significantly reduction on the ventilator use.


AT132 has been generally well-tolerated and has shown a manageable safety profile across both dose groups.  There have been no possibly or probably treatment-related serious adverse events reported in Cohort 1 since the scientific update in May 2018.  There have been eight possibly or probably treatment-related serious adverse events reported in Cohort 2.  This included: a case of Cholestasis (a condition where bile cannot flow from the liver to the intestine), vomiting, nausea, fever and thrombocytopenia (low levels of thrombocytes, also known as platelets, in the blood),  and mild myocarditis (inflammation of the heart muscle). All these effects have been successfully managed with medicines and patients have not shown any other health problems after that. 

Next steps

The gene therapy AT132 will be tested in more children to select the optimal dose. Hereafter, Audentes plans to further discuss with the FDA and EMA to gain approval of this therapy and be able to introduce it the market in the US and Europe.

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