I like to start all my scientific inquiries off with really dumb questions. It makes life more fun. Here’s my latest: why can’t we just give steroids to people with muscular dystrophy?
It makes sense, right? Steroids make people look like this:
Muscular dystrophy makes people look like this:
Mix the two together and you should have a guy that looks like this:
This is a really dumb question because this obviously doesn’t work. If it did, muscular dystrophy wouldn’t be such a difficult condition to treat. But…why?
Well, it has to do with how muscles are built. Muscles, like most parts of your body, start off as mesenchymal stem cells. These are cells in your bone marrow which can differentiate into bone, cartilage, muscle, or fat cells. They depend on a pretty complex mix of signals to tell them which cells to differentiate into at which time.
Muscle is energetically expensive to maintain. As we evolved in an environment in which calories were hard to come by, your body defaults towards keeping the minimum amount of muscle necessary to meet bodily demands, which it somehow monitors based on muscle stress (this part is a little hazy in the literature). That’s why people who are bedridden for as little as 72 hours lose about 15% of muscle mass.
When your body does demand more muscle mass (e.g. in response to weightlifting stress), it uses hormones as the signal to differentiate more mesenchymal stem cells into muscle. This is why testosterone briefly increases after resistance training in both men and women. Anabolic steroids are a way of just injecting that signal directly into the body, which is why men who use steroids and don’t work out gain more muscle than men who don’t use steroids but do work out.
So steroids just increase the amount of signal, which means more stem cells get converted into muscle. This isn’t an effective treatment for muscular dystrophy because the problem is further down the chain.
Here’s what I mean. When stem cells get converted into muscle, they end up being converted into something that looks like this:
Note how you’ve got a bunch of tubes in a sausage casing, basically. Everything is powered by the embedded mitochondria, which go around the tubes. In muscular dystrophy, this structure gets messed up. Most commonly (i.e. in Duchenne muscular dystrophy and Becker muscular dystrophy), the tubes aren’t properly encased in the sausage. They’re missing a key part of their casing (the protein dystrophin), which means that the tubes are leaky, and their excess calcium leaks out and into the mitochondria, causing them to burst. No mitochondria means no power, so the muscles just die.
Recruiting more stem cells into muscle cells isn’t going to help. Whatever muscle cells you create will still have leaky tubes, and their mitochondria will still die. It’d be like if you had a construction project, and you found out that all of the wooden beams you were receiving from a supplier were rotten. Would you order more beams from that same supplier to fix the problem?
What’s interesting is that, at this point, this might seem pretty obvious. However, the whole field of muscular dystrophy got stuck along a very similar path for about a decade.
It started when people started looking into myostatin. Myostatin is a brake on muscle growth which prevents overgrowth, or hypertrophy, of muscles. Inhibiting myostatin is like removing the brake. For example, dogs that do not have myostatin look like this:
Following really similar logic to our steroids example in the beginning, pharmaceutical companies poured over a decade of work (from 2006-2018-ish, so pretty recently) and over a billion dollars into trying to make myostatin inhibitors work in muscular dystrophy. The end result, in retrospect, was predictable: they successfully cured muscular dystrophy in mice, but not in humans.
More promising approaches towards curing muscular dystrophy involve creating dystrophin or rescuing mitochondria, although those are much more difficult and complicated to do than inhibiting myostatin or administering steroids. It remains to be seen how successful those approaches will be. Stay tuned!