79 Nick Catlin Thursday, 27 November 2014 No Comment

In the 1850's Guillaume-Benjamin-Amand Duchenne (de Boulogne) discovered Muscular Dystrophy. In fact, the original name of this disease was Duchenne Muscular Dystrophy, named in his honor.

But it took until 1986, for the gene dystrophin to be cloned, until we had a real scientific basis for understanding the mechanisms underlying the severe muscle wasting first seen by Duchenne over 130 years before.

It is very important to understand how mutations or faults in the gene result in a lack of protein called dystrophin being made to support the healthy growth and maintenance of muscle tissue.

from Dr. Annemieke Aartsma-Rus
Dr. Annemieke Aartsma-Rus gives us all an excellent explanation of how genes in our chromosomes code for essential proteins like Dystrophin.

What is of real significance to understand is that mutations in this particular gene, the largest in our genome, results in a catastrophic loss of a protein that in the long term gives rise to severe muscle wasting and also in some cases cognitive problems.

Annemieke's cartoon of the 79 exons shows a deletion of exons in the dystrophin gene that will mean the information can not be read and translated into a functional protein.
At first it was hoped that the dystrophin gene could be simply replaced. However since 1986 it has become apparent that due to the size of the gene and it's widespread distribution in muscle cells around the whole body the task of replacing the faulty gene has been a far greater challenge than scientist first expected.

In terms of gene therapies a great deal of work has focused on finding ways and means of snipping out an exon (exon skipping) to make the gene readable or in the case of very small single base pair mutations to find a drug to promote read through of the gene. Annemieke explains this very well.
Where antisense drugs (AON's) put the exon gene sequence back in frame to produce a functional but shorter protein. 

Or in the case of Translarna to read through a single point variation.

The use of viral vectors to deliver mini genes are also now in development and moving towards clinical trials. This would essentially replace the gene that is not able to function with a mini gene, again due to the size of dystophin, that can produce a functional protein.

Utrophin is a gene that is similar in the body to dystrophin and another potential therapy would be to up regulate utrophin so that it might be able to compensate for the lack of dystrophin.

Jon Tinsley explains Summits approach with their SMT C1100 drug now in clinical trial.

There are other potential therapies and drugs in clinical trial and Treat NMD gives an excellent overview.

Progress is being made and our understanding since Duchenne identified the condition over 150 years ago has accelerated in the last 20 years. However only one novel medicine for Duchenne, Translarna, has gained market approval in Europe and only for a small group of patients. 
79 is hosted by Nick Catlin

Nick Catlin has a son Saul who has Duchenne Muscular Dystropy. He is a founding member and previous CEO of the Charity Action Duchenne. Nick now works with young people with Duchenne and their families at Decipha assessing for Special Education Needs and advising on reviewing Education Health and Care Plans.

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