Myostatin – The Hercules gene, potential treatments, and fitness lies?

What is myostatin?

Myostatin is a myokine which is a small protein encoded by the MSTN gene that is produced and released by muscle cells, these myokines then act on the muscle cells around it and on the origin cell itself. Myostatin acts as a limiting factor for muscle growth, in other words more myostatin = less muscle growth. There is a very good reason for this, though it seems counter intuitive at first; from an evolutionary perspective it is not actually beneficial to be huge and muscular. The more muscle you have, the higher your metabolic rate, the more energy you burn, this occurs even when you sleep. In a time when food was sparse and considerable effort was required to find your next meal we need this energy to keep our organs running, especially our beautiful big brains. This is not to say that muscle strength isn’t important, but it needs to be balanced. Although we are considerably weaker than other primates of the same size such as Gorillas and Chimpanzees, it has been suggested that our comparably week strength is an evolutionary trade-off for our remarkable brains.  Additionally huge muscle growth limits our movement, picture The Mountain from Game of Thrones chasing down and catching a Deer through a couple of miles of woodland and you get the picture.

Myostatin mutation – The Hercules gene

Myostatin attracted a lot of attention in the 1990s when a phenomenon known as double muscle syndrome was observed in sheep and cattle. As the name suggests these animals appeared to have twice the muscle mass of your average beast.  This is due to a mutation in the MSTN gene. There have since been two humans born with a mutation in the MSTN gene. Who gained wide spread attention in the media at the time, being called “Super babies”.

In 2007 the discovery of a new mutation in whippet dogs was published calling the dogs the “Bully” whippet.  The dogs that had two copies of the MSTN mutation had the ”double muscled” phenotype while dogs with one copy of the mutated gene were still much more muscular and much faster than average.

Why is this important?

If there is a gene, we can edit it. This means that there is huge potential for the treatment of muscle wasting diseases like AIDS and muscular dystrophy and with revolutionary systems such as CRISPR –Cas9 these endeavours are becoming easier.

Editing the genome of a single cell is relatively simple, the challenge occurs with attempting to change the DNA of a living adult where cells number in the trillions. Viruses are a great way to do this because they target specific cells and edit genomes by default, for example the Rhino virus which causes the common cold targets epithelial cells in the upper respiratory tract, and this is why you get that nasty runny nose.  All we have to do is engineer the right virus for the right cell. We can put the DNA or RNA that we want into a virus and it will deliver it for us. This can be done in one of two ways: incorporate genes that produce proteins that interfere with the myostatin pathway, or deliver a CRISPR-cas9 sgRNA that will interfere with the MSTN gene itself, thus rendering it ineffective. A good example of this is a study that incorporated MTSN interfering CRISPR – Cas9 into a virus and injected it into mice with cancer. The study showed that mice treated with the CRISPR-Cas9 virus showed significant muscle size and strength compared to those without. You can find a video giving an overview of viral vectors here.

Another approach is the use of pharmaceuticals. The idea is to create a drug which introduces an agent to the body that neutralises myostatin chemically. These are typically some form of antibody which binds to myostatin preventing it from binding to its receptor, rendering it ineffective. Drugs are where the money is so it is no surprise that this approach has become popular with multiple big pharma companies such as Pfizer and Novartis all taking a shot.

This why we can’t have nice things – Myostatin and the fitness industry

Fast forward to today and I’m sure you can guess where the public spotlight of this gene has shifted to.  If you type myostatin inhibitor into google the first things you will see are bodybuilding supplements who claim to have the winning formula for muscle growth. Now I’m not here to give a supplement review, but what I will say is that these supplement companies, these unsung heroes, these vanguards on the forefront of medical science seem to have cracked several years ago a drug that is still in clinical trials in the biggest pharma companies in the world *cough bullshit*.

It is feared that myostatin inhibitors will become the new performance enhancing drugs, following the Bully Whippet paper there were even concerns being published by the media of the genetic doping of race dogs. Are these fears well founded? Yes probably, it’s estimated that there are around a million steroid users here in the UK. It seems like a pretty good assumption that if a magic pill arose which had fewer side effects or was cheaper or harder to detect than conventional steroids then of course they are going to use it. But this should not subtract from the enormous potential for good that this drug would yield and this is where our focus should be. After all assuming that a million steroid users switch from steroids to myostatin inhibitors, you still have one million people taking performance enhancing drugs with addition to a really good treatment for muscle wasting diseases. As always it comes down to risk vs reward and the development of this potential treatment leaves me exited for the future of medicine.