New FDA Approval: Radicava
The treatment of amyotrophic lateral sclerosis (ALS).
How it Works
Edaravone is a radical (pun intended) drug that got rapidly approved for the treatment of amyotrophic lateral sclerosis, or ALS. Yes, that ice bucket challenge thing.
The mechanism isn't exactly clear, but it's thought to be through the antioxidant properties of the drug. Given that oxidative stress leading to neural damage is considered a probable cause of ALS, this would seem to make sense.
Right now, you're probably thinking, "Wait, slow down! What's oxidative stress? And how do antioxidants work? Should I be eating more blueberries?"
We'll start with question #3. Yes. Blueberries are delicious. And they make your mouth blue. Eat enough and you'll have your own show banging drums of paint in Vegas.
So back to question #1. Oxidative stress. Basically, to really tl;dr all of this, your body is an amazing feat of engineering and chemistry. But like any well-run factory, unwanted byproducts can occur that you need to get rid of (and there aren't any backwoods streams to dump these in).
In the body we have some reactive oxygen species, better known as free radicals. Think of them as hippies running around your body and destroying things. The "free radical" portion is basically an unpaired electron that's just looking for a friend.
That then takes us to question #2. How do antioxidants work? Antioxidants welcome the free radicals' lonely electron with open arms, un-radicalizing (not sure that's a word) them.
That being said, keep in mind that our immune system also harnesses free radicals to attack pathogens. And we use radicals in some of our biological processes (so you may be able to predict some of the upcoming side effects of edaravone). Not all radicals are bad. Some hippies are good.
What does this have to do with ALS and edaravone? We'll start with ALS. Oxidative stress is thought to be behind quite a few diseases. For ALS particularly, oxidative damage of the neurons is thought to be a cause of the disease, so combating this oxidation would theoretically slow the disease.
Edaravone is a pyrazolone free-radical scavenger, or in simpler terms: "antioxidant." It's been used for years in Korea and Japan under the brand Radicut for the treatment of acute ischemic stroke (also thought to be due to oxidative damage of neurons). Overseas, it's actually shown moderate to significant improvement in function after a stroke.
And so some 'stroke' of genius caused someone to consider the potential role of edaravone in the treatment of ALS. Alright, no more puns (I promise).
For those chemistry nerds out there, the antioxidative properties can be seen in the chemical structure of the drug. If you remember your early pharm-chem lectures, you'll see that the lactam ring on the edaravone acts as an electron acceptor, ultimately becoming hydrolyzed to neutralize the radical.
Notable Adverse Effects
There's limited data with use in the US for ALS, but in the clinical trials so far, patients taking edaravone have experienced:
- Shortness of breath (not good in ALS patients)
- Bruising and gait disturbance
Notably, acute renal failure was sometimes seen when Edaravone was used for acute ischemic stroke, so take that how you will.
Current Place in Therapy
ALS is essentially an untreatable disease at this time. The best we can do is slow it down as much as possible, treat the symptoms and the effects of the disease (i.e. respiratory function, paralysis, incontinence, and psychologic effects such as depression etc...).
You might remember that scene in Dr. Strange (the movie), where the Ancient One talks about changing every outcome except for that moment she's in? Or for you Community fans, the dice and the timelines?
That's sort of the way ALS treatment goes. You do everything you can to prevent progression and to prevent unwanted outcomes. But for right now (at least), the prognosis isn't great. One hopes to slow down the disease (or time) long enough for a new breakthrough that might reverse, or at least stop the disease.
This is a novel therapy in a field that's been long overdue for a breakthrough. It's a fairly new drug, but given the lack of options it's probably going to be picked up and used fairly quickly and often.
But that's just my opinion. The jury is still out, and other promising therapies are still in the pipeline so here's to hoping.