Gene therapy trial for Duchenne Muscular Dystrophy

dmd

Duchenne and Becker muscular dystrophy are both caused by mutations in the same dystrophin gene.

How it this possible?

Well, the genetic code which is translated to from proteins “talks” in words made of three letters (base pairs).

dmd dna

A gene mutation that deletes only one or two base pairs, or worse still signals the end of the word (known a “premature stop codon”) will result it a very abnormal dysfunctional gene product, leading to complete deficiency of functioning dystrophin, and the more severe Duchenne Muscular Dystrophy.

dmd muscle bx

Normal muscle bx (a) vs Duchenne muscular dystrophy (b) with complete absence of dystrophin (d)

However a gene mutation (deletion) that removes base pairs in a multiples of three is called an in-frame mutation, and causes a (sometimes only minor) qualitative change in the dystrophin protein, leading to the milder Becker’s muscular dystrophy.

Ataluren (also known as PTC124) is a small molecule designed to overcome premature stop codons.

alturen

Put simply, the idea is that it might convert some Duchenne boys in to a milder form (more like Becker’s) of muscular dystrophy by allowing them to produce some more normal dystrophin.

The drug can only help boys affected with premature stop codons confirmed by DNA testing.

The drug is currently undergoing Phase III trialsClick here for more information.

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