Correlative genetic analysis shows: exon 44 skipping-amenable DMD has a later loss of ambulation (LoA)

07/31/2016

- an important finding for the implementation of clinical trials. To specify the natural disease progession of Duchenne Muscular Dystrophy (DMD) patients and the mutations in the Dystrophin gene Sebahattin Cirak, leading a DFG Emmy Noether research group at the CMMC, and his international

 

colleagues correlated the different truncating DMD gene mutations in a large, prospective natural history study with the time loss of ambulation (LoA).

Duchenne muscular dystrophy (DMD) characterized by progressive muscle weakness and wasting is a lethal, incurable X-linked recessive disorder. DMD is caused by frame-shifting mutations in the Dystrophin gene and common with a frequency of 1:3500 in males. DMD often occurs in people without a known family history of the condition.

So far no approved cure is available for DMD. The investigations of the gene mutations as well as the underlying molecular mechanism show potential for therapeutic targets and have been show promise in early phase of human clinical trials (Cirak et al., 2011, The Lancet).

This correlative study revealed that exon 44 skipping-amenable DMD has a later loss of ambulation (LoA) and that mutation-specific randomization and the selection of placebo groups are essential for the success of clinical trials. The finding of the international research team are of importance for the implementation of clinical trials that will verify if exon skipping may be useful way of treating DMD. 

The work is published in the scientific journal Neurology

DMD genotypes and loss of ambulation in the CINRG Duchenne Natural History Study.
Bello L, Morgenroth LP, Gordish-Dressman H, Hoffman EP, McDonald CM, Cirak S; CINRG investigators. Neurology. 2016 Jul 26;87(4):401-9. doi: 10.1212/WNL.0000000000002891.

Further details, please contact the corresponding author:
Dr. Sebahattin Cirak
Sebahattin.Cirak[at]uk-koeln.de