New Targeted Therapy Shows Promise for Duchenne Muscular Dystrophy


Duchenne Muscular Dystrophy (DMD), also known as Pseudohypertrophic, is one of nine types of muscular dystrophy, a degenerative disease that primarily affects voluntary muscles and causes generalized weakness and muscle wasting. In 1986, researchers identified the gene mutation causing DMD and further identified a protein called dystrophin in 1987. Today, researchers from the Neuromuscular Centre, UCL Institute of Child Health in London have discovered a targeted antisense therapy that could restore expression of dystrophin, bringing hope to the many sufferers of the disease.

Researchers Call the Trial a Significant Milestone in Finding Treatment for DMD

Professor Francesco Muntoni and his team enrolled 19 young Duchenne patients (mean age 8.7) in a Phase II trial in which the participants were given 12 weekly infusions of phosphorodiamidate morpholino oligomer (AVI-4658), developed by AVI BioPharma. When the treatment was complete, a muscle biopsy was taken from each child.

Duchenne Muscular Dystrophy results from a deletion and other mutations in exon 51 of the dystrophin gene. Dystrophin is a protein that is needed for the preservation of muscle tissue. Its loss causes inflammation and deterioration of the tissue. AVI-4658 is thought to act as a “molecular scalpel” which removes the damage and restores dystrophin production in a technique known as “exon skipping”.

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Seven patients out of the 19 had significant favorable response to the trial. The three patients with the most notable responses had 15%, 21% and 55% of muscle fibers that stained positive for dystrophin after the treatment. Prior to the AVI-4658 injections, these children had fewer than 5% of these fibers.


In general, the treatment was well tolerated, even in single doses up to 900 mg. There were no serious adverse effects seen in the lungs, liver, kidney, or bone marrow. The researchers described this safety profile as “encouraging”, but warn that the drug was only administered for a short time during this trial. In clinical practice, the treatment would need to be given over the patient’s lifetime.

Professor Francesco Muntoni, said, “I've worked with patients with Duchenne muscular dystrophy for many years and this is the first time we can say with confidence that we've made a significant breakthrough towards finding a targeted treatment”.

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Drs Akinori Nakamura and Shin’ichi Takeda agree, writing in a commentary accompanying the study, published in The Lancet. "This study is a milestone in the feasibility of systemic exon-skipping therapy for Duchenne muscular dystrophy,” they conclude, adding that the discovery could “have a great effect on the development of treatments for other intractable hereditary neuromuscular disorders.”

DMD is one of the most common fatal genetic disorders affecting children. The condition primarily affects boys, who inherit the disease from their mothers through the X chromosome. Approximately one in every 3,500 boys worldwide is affected. The condition is terminal, with death usually occurring before age 30.

Journal References:
Cirak S, et al "Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study" Lancet 2011; DOI: 10.1016/S0140-6736(11)60756-3.

Nakamura A, Takeda S "Exon-skipping therapy for Duchenne muscular dystrophy" Lancet2011; DOI: 10.1016/S0140-6736(11)61028-3.



Good results are 55% and 21% of muscle fibres, but nothing is reported about a possible improvement of walking ability.