Download DMD Reviews 91 - Action Duchenne

Research Review No. 91.
An interesting review.
The Studies:
In the latest issue of Frontiers in Bioscience-Landmark, there is a very
useful and comprehensive review of the genetic therapies for Duchenne
Muscular Dystrophy (DMD), which are published in the world literature. The three
French researchers who co-authored this review are experts in this field of
endeavour and therefore their views on the various treatments for neuromuscular
disorders (NMD) are very valuable. They state at the opening that: “In this
review, we will focus on the main advances in gene therapy and RNA-based
approaches for the treatment of NMDs. In their review they concentrate on DMD
and Spinal muscular atrophy (SMA), but I will restrict myself to DMD.
While there is currently no effective therapy to prevent or affect the
gradual muscle loss associated with DMD they consider that the studies, which
“include gene therapy aiming at reintroducing a functional recombinant version of
the mutated gene using adeno-associated, lentiviral or adenoviral vectors, as
well as RNA-based strategies using antisense oligonucleotides (AONs)”. They
consider that these hold great promise for the future and they discuss the clinical
trials currently in progress especially for DMD.
They discuss and describe the studies currently in progress in which “a
DNA coding sequence (cDNA) from a native gene, constructed and designed to
be transcribed and then translated into a protein to compensate the deleterious
effect of the mutated form directly or indirectly responsible for the genetic
disorder.” However a present the problems of introducing the full gene for
dystrophin is raising problems. Nevertheless these problems are not considered
unsurmountable. Various viral vectors and other modes of introduction of the
gene for dystrophin are in progress and showing promise. There is also progress
reported in overcoming the immune responses to the introduction of a ‘foreign’
virus into the human body.
Exon skipping has been discussed for many years since it was first
demonstrated in 1996 and “Since then, numerous in vivo studies have provided
pre-clinical evidence for the therapeutic potential of an antisense strategy for
DMD in several animal models”. The authors follow their discussion by stating
that: “Following the encouraging results obtained on these animal models,
antisense mediated exon skipping has rapidly moved towards clinical evaluation
in DMD patients.” They proceed to describe these investigations in detail.
The authors’ final conclusions sound very positive and I quote their final
sentence in full: “With continued success, we will hopefully see a gradual
implementation of new therapies over the coming years that will increasingly
extend lifespan and improve the quality of life for patients with neuromuscular
diseases”.
Reference:
1)
Benchaouir, R., Robin, V. & Goyenvalle, A. (2015) Gene and splicing
therapies for neuromuscular diseases. Frontiers in BioscienceLandmark. 20:1190-1233.
Karl A. Bettelheim
8.6.2015