New Gene Therapy to Fix Dystrophin Deficiency in DMD Shows Promise in Mice, Study Shows

New Gene Therapy to Fix Dystrophin Deficiency in DMD Shows Promise in Mice, Study Shows

Researchers at the University of Missouri have developed a new method to efficiently deliver the correct form of dystrophin gene to muscles as a way to correct the faulty gene that characterizes Duchenne muscular dystrophy (DMD), a mouse study shows.

Their study, “A Five-Repeat Micro-Dystrophin Gene Ameliorated Dystrophic Phenotype in the Severe DBA/2J-mdx Model of Duchenne Muscular Dystrophy,” appeared in the journal Molecular Therapy—Methods & Clinical Development.

DMD is caused by a modification of the gene that encodes the dystrophin protein, which is essential for normal muscle activity. Such mutations interfere with production of the functional protein, severely affecting muscle fiber structure and strength.

Correcting the faulty gene could potentially treat this disease. Several attempts at gene therapy have been tried, but all have failed to efficiently reverse all DMD symptoms.

Gene therapy commonly uses vectors based viral genetic sequences to achieve the desired gene transfer capacity. The therapeutic potential of these techniques rely not only on the delivery system, but also on the sequence of the gene of interest that is used. In this case, smaller versions of dystrophin known as microdystrophin must be used, since its natural form is just too big to be useful in gene therapy.

“There have been other gene-transfer vectors attempted in the past (such as adenoviral vector, herpes simplex virus and plasmid), but they have largely been unsuccessful due to the complexity of the disease, challenges associated with delivery, and the large size of the native dystrophin gene,” the study’s senior author, Dongsheng Duan, said in a news release.

Duan’s team used an engineered form of the adeno-associated virus (AAV) vector to replace the damaged gene specifically in the muscles.

Researchers also used a version of the dystrophin gene that can potentially minimize the toxicity signs commonly associated with such methods, such as inadequate blood supply and fatigue during muscle contraction. This AAV viral vector has also been used in the past, but this is the first time researchers have combined it with such a version of dystrophin.

This strategy boosted levels of dystrophin protein in the muscles of mice models of DMD, and significantly reduced some disease symptoms. Yet researchers could not accurately measure the impact of this new potential therapy to correct DMD-associated effects on the hearts of the animals.

“Human studies have shown that one-time intramuscular injection of an AAV vector can result in the expression of a therapeutic protein for many years. For example, a study showed Factor IX expression for 10 years in a hemophilia patient,” Duan said. “In preclinical studies in murine and canine models, we have also observed persistent multiyear microdystrophin expression from AAV vectors. In the case of mice, a single injection can lead to microdystrophin expression throughout the lifespan.”

13 comments

    • Alice Melão says:

      Dear Erica, unfortunately it is impossible for us to estimate the timeline of clinical development of a new therapy such as this one. But usually these processes require quite some time to fulfil all regulatory pre-established safety and financial requirements.

  1. Michael Smith says:

    There’s no reason why this wouldn’t work on other types of MD. It actually might be more effective on other forms. So why, once again, do they always box these treatments to just Duchenne’s? I just don’t understand it.

  2. Giriraj Sharma says:

    When it will be available for human and what time it will take.if possible let me know about it.Its very Urgent.

    • Tim Bossie says:

      At this moment we do not know when this will be taken to human trials. However, we will continue to monitor this and report on it when this information becomes available.

  3. Rakesh Kumar says:

    My son Shivam Anjay 19 years patient of Duchene Muscular Dystrophy(DMD),weight 18 kg. DNA was evaluated for declaration of 22 exon in Dystrophin gene, 46 to 50 exon in Dystrophin gene found deletion but 45 and 51 were found present. This gene therapy will be applicable or not. I live in India, Bilaspur, Chhattisgarh 495006.

  4. Anna cantu says:

    I just want to say thank you for all your hard work. I know God is working and he brought wonderful genius such as you I know God is at work and we will all see positive results very soon to help our children Thank you

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