Do you remember the ice bucket challenge?

I hope so… I mean, we did it. Well, f you don’t remember, welcome to what the internet did for fun in 2014.

We justified it because it was for charity – specifically, for research into ALS. But if you were there, did you ever ask yourself whether all that money would actually bring about any kind of change, or whether it was just a meme that made us feel good? Well, I’ve got great news for you.

The money raised is leading to real breakthroughs. And we’re going to dive into one of them: the discovery of a gene related to the internal scaffolding of cells, and how strengthening that scaffolding could work as a treatment for ALS. [♪ INTRO] The ice bucket challenge raised $115 million for The ALS Association back in 2014. According to als.org, over 17 million people participated in one way or another.

The whole thing was great fun for a really great cause, and seeing our favorite creators get ice water dumped on them was kind of the cherry on top. At least until researchers started putting that money to use and coming back with some findings that are one day going to make a real difference to those with ALS. ALS is short for amyotrophic lateral sclerosis and is sometimes also known as Lou Gehrig’s disease.

A legendary Yankees first baseman, in case you were wondering. ALS is a rare disease that affects motor neurons – the nerve cells in the brain and spinal cord that allow us to control voluntary muscle movement. Things like walking, talking, and chewing.

ALS is a progressive disease, meaning it gets worse over time. Motor neurons begin to degenerate and die, meaning that they stop relaying messages to muscles. In the early stages of the disease, that causes the muscles to weaken.

Over time, patients will experience symptoms like twitching, cramping, and atrophy of the muscles. Eventually, the person loses their ability to move altogether. The mean survival time for someone with ALS is two to five years after onset, but some people live ten years, or even longer.

Right now, there’s no cure, and very little in the way of treatments to slow it down. So clearly, any breakthroughs that could help us find a treatment to improve this outlook would be a huge step. The ALS Association funneled ice bucket money into, among other things, projects doing big searches of the genome to find new genes and new gene variants related to ALS.

One of these newly implicated genes is called NIMA-related kinase 1, or NEK1. Scientists have found that around 2 to 3 percent of ALS cases occur in patients with at least one non-working copy of NEK1, but they didn’t know exactly why. In a 2023 paper in the journal Science Advances, researchers presented a series of experiments looking for just what NEK1 talks to in the cell, which might help them understand how and if it’s related to the motor neuron breakdown we see in ALS.

Their experiments showed that NEK1 physically interacts with microtubules. I know what you’re thinking – man, I hate it when things mess with my microtubules. Yeah, me too.

Microtubules are rigid, hollow rods that are about 25 nanometers in diameter. These tiny rods help support the cell, kind of like scaffolding. Also like scaffolding, they can be broken down and rebuilt elsewhere to suit the cell’s needs.

And they’re especially important for neurons, because there’s a big ol’ bundle of them in the important signaling structure called the axon. They’re giving the axon its shape and strength, without which it wouldn’t be able to pass messages along. When you mess with microtubules, axons become less stable, and prone to collapsing.

In the paper, the team showed that if cells don’t have enough NEK1, the axons of motor neurons are shorter and less stable. Which definitely looks a bit like ALS! Microtubules also help cells move things around.

Specifically they help transport stuff between the nucleus and the rest of the cell, which is important if the nucleus is going to actually run things. The researchers showed that without NEK1, cells can’t bring stuff into the nucleus as easily. And while it’s a little less obvious how that would lead to the symptoms of ALS, it’s something other researchers have also identified – at least for certain ALS subtypes.

The researchers believe that if we can target these issues with some sort of therapeutic, we might just be on to something big. Now, this alone doesn’t mean that we’ve cured ALS. Like I said, NEK1 is only implicated in about 2 to 3% of ALS cases.

And while that doesn’t sound like much, it’s not the whole story. You see, the genetics behind ALS vary a lot, person to person. To the extent that one of the biggest debates in the field is whether ALS is one cohesive disorder, or lots of really similar-looking disorders in a trench coat.

However, no gene works alone – they have friends. Every gene works together with a bunch of other ones. Protein A passes a signal from outside the cell to protein B, which sends protein C to the nucleus to turn something on or off in response to that signal.

Mess with A, B, or C, you can get the same result. And when you start looking at NEK1’s friends, a lot of them are implicated in ALS, too. What’s more, a lot of other genetic causes of ALS also seem to be linked to disruptions in nuclear import.

The researchers say it’s a good thing they found similar mechanisms to other research looking into the causes of ALS. It suggests ALS is one cohesive disease. And that means you can treat it as one disease.

But wait, it gets better. A lack of NEK1 destabilizes microtubules, causing them to break down. So if only there was a way to shore up those microtubules, maybe you could rescue the axons of affected neurons.

There is. There is a way to do that that we already have and give to patients for totally different reasons. Certain cancer drugs, such as paclitaxel and laulimalide, stabilize microtubules in order to stop cell division.

You know that spindly thing your high school bio teacher pointed out pulling apart chromosomes during cell division? Yeah, that’s made of microtubules. With microtubules locked in, the treated cells can’t divide, which in cancer is what you want.

The researchers did some preliminary experiments with these drugs, and found they can stabilize microtubules made floppy by malfunctioning NEK1! Now, we’re not quite there yet. You’d still need to look into whether ALS patients would benefit from getting these drugs, and what the side effects would be like.

We’re complex, our bodies can do screwy things we don’t expect sometimes, and these are literally chemo drugs. So that needs figuring out before microtubule drugs can be labeled as a treatment for ALS. But using a drug we already have for a new purpose is just astronomically easier and cheaper than inventing a new one.

So if the ice bucket challenge leads to a way to use an already approved class of drugs to help people with ALS, chef’s kiss, man. And even if it doesn’t, the researchers say their findings make NEK1, quote, “a formidable therapeutic candidate.” That’s science for “Hey guys, we’re almost there.” Thanks for watching this episode of SciShow, and I hope it helped you understand where the money goes and what it does for these kinds of things. If you’re looking for something to watch next, you might enjoy our original Ice Bucket Challenge.

Wow… what a throwback. We’ll see you all next time. [♪ OUTRO]