Sarepta Therapeutics may have a cure out for Duschenne Muscular Dystrophy (DMD). It’s called SRP-9001, and while I hesitate to say it’s a Dragonball Z reference, I’m not sure why else it has that number. Either way it’s an interesting piece of work and I thought I’d write about it and what I know about it.

DMD is caused by a mutation in the protein dystrophin, a protein which is vital for keeping the muscle fibers stiff and sound. Our muscles move because muscle fibers pull themselves together, which shrinks their volume along an axis and therefor pulls together anything they are attached to. The muscle cell pulling on itself creates an incredible amount of force, and dystrophin is necessary to make sure that that force doesn’t damage the muscle cell itself. When dystrophin is mutated in DMD, the muscle cells pulling on themselves will indeed begin to cause deformations and destruction of the muscle cell itself, which leads to the characteristic wasting away of DMD sufferers. The expected lifespan of someone with DMD is only around 20-30 years.

Dystrophin is a massive protein, fully 0.1% of the human genome is made up of just the dystrophin gene. However a number of the mutations which cause DMD are point mutations, mutations in a single DNA nucleotide. If just that one nucleotide could be fixed, in theory the disease could be cured. For a long time genetic engineering and CRISPR/Cas9 has targeted DMD for treatments based on this idea of just fixing that one nucleotide.

However, Sarepta seems to be working on an entirely new theory. Deliver a complete gene to the patient which can replace the functionality of the non-functional dystrophin. This is called micro-dystrophin and it is less than half the length of true dystrophin. However it still contains some of the necessary domains of dystrophin like the actin-binding-domain. This is important because of how genetic engineering in humans actually works (these days). How do you get a new gene into a human? Normally, you must use a virus. But the viruses of choice (like AAV) are actually so small that the complete dystrophin gene simply would not fit in them. Micro-dystrophin, being so much smaller, is needed in order to fit the treatment into a virus.

So the idea would be that DMD patients cannot produce working dystrophin, but when SRP-9001 is given to them it would give them the genes to create micro-dystrophin for themselves. Then once their muscles begin creating this micro-dystrophin, it would spread throughout the muscle cell and take up the job of strengthening and stiffening the muscle cell just like normal dystrophin does. In this way the decay of their muscles would slow and hopefully they’d live much much longer.

SRP-9001’s road to FDA approval is not yet fully formed. They’ve done some nice clinical trials where they’ve shown that their genetic engineering drug does successfully deliver micro-dystrophin genes into the patients, and that the patients then use those genes to produce the micro-dystrophin protein. However as of right now they are still doing Phase 3 clinical trials and still awaiting the FDA to give them expedited approval. That approval won’t come until June 22nd at the earliest, but I believe it would still make it the first FDA-approved treatment for DMD.