| Immune response against dystrophin |
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The immune system will attack foreign invaders (bacteria, parasites, viruses etc). It recognizes these invaders because they have proteins that are not found in the human body. Duchenne patients do not make the dystrophin protein, so there is a possibility that the immune system of patients will see dystrophin as a threat once a therapy can successfully induce dystrophin expression (it is an unknown, new protein). Most Duchenne patients produce a low level of dystrophin (through spontaneous exon skipping). The number of these “revertant fibers” is too low to prevent the disease, but this means that dystrophin is not entirely new, as the immune system will have seen it before. |
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In the gene therapy trial, an immune response to dystrophin has been observed to the new microdystrophin in 4 of 6 treated patients. This has implications for gene therapy, but perhaps also for other therapies that aim to induce dystrophin (e.g. exon skipping and forced read through). |
| There are, however, a couple of things to bear in mind: |
| 1. |
As a viral vector is used to deliver the micro-dystrophin, the immune system is already on high alert (the viral vector is observed as a foreign invader – the body does not know this time it has good intension). Consequently, it is probably more likely to also attack the dystrophin. |
| 2. |
The micro-dystrophin is an artificial, much truncated protein that is more likely to elicit an immune response than dystrophin formed after exon skipping or forced read through. |
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Nevertheless an immune response against dystrophin cannot be completely ruled out for other therapeutic approaches and is therefore carefully monitored in the exon skipping and ataluren trials. So far, no anti-dystrophin immune response has been reported in exon skipping and ataluren trials. |
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