In reality, it's all about the science.... @UboyThanks Uboy, the...

In reality, it's all about the science.... @Uboy

Thanks Uboy, the blog is simply invaluable. Lets follow some of the science and join some dots. Reference is made in the blog to the accumulation of extracellular matrix around the muscle fibres such that after a period of time the loss of muscle function is linked to fibrosis rather than the original mutation in the dystrophin gene.

Lets also highlight the point that the phenotype of a cell is more than its DNA sequence but includes the concentration and locations of all the different protein components.

Here's the kicker. Lets now return to the article Thrombospondin 1 in Metabolic Diseases. The authors make the point that TSP-1 largely contributes to the rapid remodelling of the extracellular matrix through the inducement of profibrotic genes or by activation of latent TGFβ1. We appear to be on the same planet talking about the same extracellular matrix. And, along comes ATL1102.

The mechanism of action of ATL1102 includes the downstream modulation of the concentration of different protein components but in particular TSP-1 and LTBP4 that sequesters TGFβ to keep it latent. One by down regulating and the other by up regulating.

Gene therapy has missed the mark because restoring the wild type dystrophin gene is the equivalent of shutting the barn door after the horse has bolted. Of course we also need to remember that micro-dystrophin isn't the equivalent of wild type dystrophin but comes with baggage.

The more we discover about ATL1102 the more it looks like an effective treatment for DMD not simply for its role in modulating lymphocytes and managing the inflammatory process but because of the downstream modulation of several proteins critical to fibrosis.