Myotonic Dystrophy Steinert disease

 

 

 

 

 

 

2013 - 2012 - 2011 - 2010 - 2009 - 2008

2011 ARCHIVES

December 2011 - Summary of the congress of IDMC-8
The 8th meeting of the international consortium on myotonique dystrophy (IDMC-8) been held in Tampa (Florida) from November 30th till December 4th, 2011.


Treatments for myotonique dystrophy type 1


Therapy based on antisense oligonucleotides
Several teams demonstrated the proof-of- principle of a therapy based on the subcutaneous injection of antisens oligonucleotides in myotonic dystrophy type 1. The team of Rochester, aimed by the Dr Charles Thornton, showed that the destruction of toxic RNA, by injection subcutaneous of oligonucleotides in a model of mouse DM1, was able of restoring some manifestations of the disease such as myotonia and muscular impairments. These encouraging results acquired in a mouse model of DM1, require however, to be confirmed in other mouse models. The oligonucleotide muscle delivery still remains the problem to be solved before being able to go in clinical trial. Various approaches were assessed, as the use of peptides coupled with oligonucleotides or the coating of oligonucleotides in lipid emulsions. These approaches showed that it was possible to increase the delivery of oligonucleotides into skeletal muscles, at a level, however, insufficient for therapeutic benefit.


Beside the use of oligonucleotides, several other approaches were assessed such as the use of small molecules. The problem of these approaches remains the toxicity of these molecules. They cannot be used in a near future but could open new therapeutic avenues.

Ritalin as treatment of excessive daytime sleepiness in the myotonic dystrophy type 1.

The team of the Dr J Puymirat showed the effectiveness of 20 mg / day of Ritalin as treatment of sleepiness. Medicament was well tolerated without major side effects.


Treatment of cardiac conduction defect: Pacemaker or defibrillator?
The question was discussed during this meeting. The American team of the Dr WJ Groh, recommends the implantation of defibrillator for the treatment of cardiac conduction defects and of the bradycardia. On the opposite, the team of Pr Duboc (Paris) recommends the implantation of permanent pacemaker in cases where ECG shows cardiac conduction defect or a preventive pacemaker in subjects having had an invasive exploration with electrophysiological study and with HV interval >70 ms. This last approach augments survival at 9 years, owed to a reduction of sudden death.


Myotonic dystrophy type 1 and cancer risk ?
Two studies, one performed at the University Maryland (Baltimore, USA) and other one in Sweden, suggest that the risk of cancer is increased in patients with myotonic dystrophy type 1. Risk would be for the cancers of the colon, brain, endometrium and ovary and ovary. A study shows that cancer risk is similar in female and male whereas the second study shows an increased risk of cancers in female gender. These 2 studies must be taken with a lot of circumspection and must be confirmed. The risk of cancers in myotonic dystrophy was very criticized owing to the methodology used in these studies.

September 2011
Where are the researches on the development of a treatment for myotonic dystrophy type 1 ?


Two different strategies have been developed. The first is the use of small molecules such as pentamidine or small fragment of DNA, named oligonucleotide, that will prevent the sequestration of proteins by the repeats. These molecules have been tested in culture and in an animal model of myotonic dystrophy type 1 with encouraging results, including improvement of some manifestations of the disease such as myotonia. This approach has, however some limitations. The specificity of this approach is not known and the toxicity of pentamidine needs to be resolved. A last limitation, is that we don’t know if the sequestration of proteins on the repeats is the only mechanism of the disease. The data obtained in mice revealed that blockage of the binding of proteins on the repeat only reproduce some manifestations of the disease such as myotonia but there is no evidence for improvement of muscle weakness. In addition there is also an increase in the levels of some nuclear proteins, such as CUGBP1, independently of the sequestration of MBNL1 on the repeats.


The second strategy is based on the elimination of toxic repeats by using some types of oligonucleotides. It is the strategy that we have developed in our laboratory since 2003. Our results showed that a single intramuscular injection of oligonucleotides eliminate up to 90% toxic repeats. This was associated with restoration in some muscle functions. The limitation of this approach is the weak penetration of oligonucleotides into the muscles after intravenous injection. This is the major goal that should be resolved before beginning clinical trials in human. All efforts are presently toward the increase in oligonucleotide delivery into muscles after systemic injection, in collaboration with different pharmaceutical compagnies. The research progress will be discussed at the next International meeting on myotonic dystrophy , which will held at Clearwater, in Florida, at the end of November.

July 2011
A recent Italian study revealed that cochlear impairment in myotoniic dystrophy type1 is present, even in patients without evidence of hearing loss at a standard audiometric analysis. Hence, in the current clinical practice, an assessment of cochlear function by TEOAE recording may be useful in DM1 patients to identify precocious signs of cochlear dysfunction. (Pisani et al., Eur J Neurology, 2011 Jul 21)

June 2011
Two recent studies revealed the existence of peripheral neuropathy in myotonic dystrophy type 1. Peripheral neuropathy is a primary event in myotonic dystrophy type 1 rather than a secondary complication of the disease. These two studies confirm the data obtained in a mouse model of the disease, showing severe peripheral neuropathy.