advanced is the research on Steinert Disease?
genetic anomaly responsible for Myotonic Dystrophy was
identified in 1992 but we have only begun to understand
how this anomaly produces the disease.
Schematic representation of a muscle
cell. In the nucleus you find
DNA (green) that carries all the genetic information.
There is a copy of the DNA inherited from our mother and
a copy of the DNA inherited from our father. This means
that each gene exists in double, one from the mother and
one from the father. In a normal cell, the gene located
on the DNA contains the information needed to produce a
specific protein but DNA can only exit the nucleus to
help in the production of proteins if it is located
within the cell body. In order to transmit the
information from the nucleus to the production site, the
cell uses a transporter (red) that we call RNA. Once it
arrives at the production site, RNA is read and a
protein is produced.
In Myotonic Dystrophy,
the genetic anomaly (blue star) is present on the DNA
that has been transmitted by the parent who carries the
disease. This DNA transmits information containing the
genetic anomaly to the RNA. This RNA, which contains the
genetic anomaly, cannot find its way out of the nucleus
in order to go to the protein production site. It thus
accumulates in the nucleus which has a toxic effect on
the cell and ultimately produces the disease.
The development of a
treatment for this disease depends on the destruction of
the abnormal transporter (RNA) which accumulates in the
nucleus. The work we are doing in our laboratory has led
to a gene medication that is able to destroy abnormal
transporters (RNA) in the muscle cells of patients with
Myotonic Dystrophy and to correct any muscular anomalies
caused by the disease. We are currently testing the
efficacy of this treatment in mice exhibiting symptoms
of the disease. Initial results indicate that the
treatment can reduce abnormal transporters in the muscle
tissue after an intra-muscular injection of the gene
medication. We must still determine if this destruction
will restore normal muscle function. If the results are
positive, a first Phase I trial on human subjects could
start in 2008-2009. This trial’s objective would be to
determine any toxicity or non efficacy of the gene
medication after an intra-muscular injection. If the
medication is not toxic, it will be possible to consider
a Phase II trial to test the medication’s efficacy.
Although our studies
are very promising, there are many obstacles that still
need to be tackled. First, in order for the gene
medication to penetrate within the muscle tissue, we
must use a transporter. The best known transporters are
inactive viruses. There are currently no known
transporters that are capable of introducing the gene
medication into the entire muscle. It is thus necessary
to consider multiple injections. Another obstacle is
that it is impossible to have the gene medication express
in all muscle groups so initial treatments will be
limited to specific muscle groups (hands, feet). Recent
research has demonstrated that certain inactive viruses
seem to be able to express a protein throughout all
muscle groups following an intravenous injection.
Finally, one last obstacle is that we do not have enough
information about the toxicity of inactive viruses in
human subjects. All these problems need to be resolved
before the start of any therapeutic trials involving
for treatment rests upon restoring the level of the
proteins that are sequestered on the genetic anomaly.
Among these proteins the most interesting one is the
muscle blind protein (MBNL). Recent studies by a U.S.
team have demonstrated that overproduction of this
protein could correct the maturation process of certain
RNAs such as the ones coded for insulin receptors as
well as for the muscle chlorine channel. This potential
treatment could be used to improve certain symptoms of
the disease such as myotonia and peripheral resistance
to insulin. It is not yet known if this treatment could
restore muscle strength.