Messing with Motor Function: The Science Behind ALS

In case you missed our post last week and in case you’ve been living under a rock for the past month, the ALS Ice Bucket Challenge has reached a pinnacle of virility not seen since Rebecca Black gave us a new way to usher in the weekend. However, unlike the meaningless funny stuff that usually turns up on the internet, the Ice Bucket Challenge has done an incredible amount of good. Apart from raising awareness of ALS (amyotrophic lateral sclerosis), nominators and nominatees have donated over $100 million to ALS research as of this writing. Compared to the $2.1 million raised in 2013, the past month has been an icy flood of cash.

But what is ALS any why have we all so enthusiastically decided that we need to drown it out? Most of us know that baseball hall of famer Lou Gehrig suffered from the disease and eventually gave his name to its colloquial identification. Some of us even know that world-famous physicist Stephen Hawking lives with the disease to this day. But what causes ALS? What does it do to a person’s body? And what can be done to stop it?

ALS is a disease of the motor neurons. There are two kinds of motor neurons: upper motor neurons (the ones in your head) and lower motor neurons (the ones everywhere else in your body). ALS starts off my damaging either the upper motor neurons, preventing them from sending signals to the spinal cord, or the lower ones, preventing them from taking messages from the spinal cord to the muscles. In the latter case, muscles in one part of the body will become weak or clumsy. In the former case a person will become more generally weak and uncoordinated.

The real problem with ALS is that it spreads and intensifies, eventually leaving a person paralyzed and without control of any of their voluntary muscles. Mercifully the disease tends not to effect involuntary muscles like those in your bowel and it often spares the muscles that control eye movement which is what allows Stephen Hawking to teach the rest of us about black holes. He uses eye movements to type academic papers and books in a monumental feat of patience. As ALS progresses it impacts a person’s ability to swallow and breath normally, often leading to death by choking.

Scientists aren’t sure what causes ALS generally, but they are aware of a type that runs in families. Research has shown that a mutation in the SOD1 gene is present in 20% of people with familial ALS. SOD1 directs the body to produce an enzyme that protects motor neurons from harmful unstable molecules called free radicals. The mutation removes this protection and causes neurons to break down. If a person has a parent with this gene mutation, there is a 50% chance they will develop ALS. Thankfully, the sporadic (non-familial) form of the disease is far less common. On average only 2 in every 100,000 is struck with ALS, usually between age 40 and 60.

As you have probably figured out by the existence of the Ice Bucket Challenge, ALS has no cure… yet. While modern treatments and technologies can help prolong patients’ lives by a few months to a few years, most people with ALS pass away within 3 to 5 years of being diagnosed. The notable exception is Stephen Hawking. Through a combination of medical intervention, help from computers, and sheer force of will Dr. Hawking has lived with ALS for over 45 years.

Modern research is focused developing gene therapies to treat mutations that can cause ALS or aims to develop chemical therapies that increase the production of antioxidants and neurotrophic factors in the body to help build and protect muscles cells. Stem cell treatments are also showing some promise. In 2008 researchers were able to take stem cells from the skin of 2 people with the harmful mutation to their SOD1 genes and raise them to produce healthy motor neurons. 

One day researchers hope to be able to grow enough motor neurons to transplant them into patients and reverse the disease's progression. The best current treatments can do is slow down the spread of ALS through the body. In rare cases ALS can burn itself out, reaching a certain point and just stopping. Scientists don’t understand why this happens but research on people for whom this is the case may also help develop treatments.

In order to do the research needed to better understand ALS and develop treatments, scientists need money. They get that money from organizations like the ALS Association, who rely on donations from the general public. So next time you see a video of one of your friends dousing themselves in water, throw them a like. And if you are nominated to do the challenge yourself, do it and make a donation. A little discomfort for you could mean a whole lot less for someone else.

Talkin’ bout Regeneration: Why can’t humans regrow limbs?

The life of a seastar (read: starfish) is a pretty enviable thing. Aside from the artistically inspired body plan, seastars get to spend their days relaxing in the ocean, enjoying the ebb and flow of the tides. They watch all manner of interesting marine life pass by overhead without ever having to worry about jobs, bills, or crooked mechanics. However, if I had to pick one thing from a seastar’s life to really get jealous about it would have to be the ability to regrow limbs.

If, during their care-free oceanic existence, something comes along that wants to make a meal out of them seastars don’t have a lot of options. They are hardly built for speed and camouflage isn’t exactly in their wheelhouse. However, if something does get a hold of them, they have the ability to detach one of their limbs and hopefully escape with the other four. Over a period of a few months or up to a year or so they can regenerate the lost limb. Not only that, the limb they left behind (if it somehow managed to escape becoming octopus food) can regrow the rest of it’s body and form a second, genetically identical seastar.

Seastars are hardly alone in this ability. Earthworms, salamanders, snail firs, some fish, and even the occasional mouse have been known to regrow complete or partial limbs. Seastars often go one step further, though by voluntarily detaching their own limbs to reproduce asexually when lady seastars are not being especially receptive to their advances.

So what’s the deal? Why do all these other animals have this clearly convenient ability while us humans are left twiddling our phantom thumbs? Well, first off, we aren’t totally outside the club of regenerative species. Many children have lost the tips of fingers or toes only to turn up at the doctor’s office a few months later with everything back in place (minus fingerprints). The interesting thing in each case where this happens is that when the fingertip was cut off some of the nail bed was left intact; and it is this fact that gives some insight into how regeneration works.

It seems that to regrow body parts, the bits that are left behind in the wake of a serious injury need to know how to communicate. If you’ve ever tried to explain to someone how to build something specific out of Lego without actually doing the work yourself, you can begin to understand how challenging communication can get in the world of construction. At the cellular level, communication falls on the shoulders of stem cells left at the site of an injury. Scientists have discovered two kinds of stem cells that do this work: somatic stem cells and pluripotent stem cells. Unfortunately, in the world of limb regeneration, not all stem cells are created equal.

Somatic stem cells can close a wound, regrow some skin, and fill in the gaps with scar tissue but not a whole lot else. Pluripotent stem cells are the real professionals. They send signals known as Wnt communications throughout the body, getting bones and even nerves involved in the healing process. These are the cells that allow structures to reform. The bad news for humans and most other mammals is that, outside of the time we spend in our mothers’ wombs, we don’t get too many pluripotent stem cells. In fact, most of the ones we are left with by the time we are born are in our hair follicles and our fingernails... It’s all starting to come together now.

Scientists aren’t exactly sure why mammals seem so deficient in what are obviously handy (no pun intended) bodily resources. Some believe that our fast metabolisms that require constant food preclude us from hiding in a dark cave for a year while our limbs regrow. Instead we have to stop the bleeding and get back to hunting as soon as possible. Others believe that the complex body plans of mammals are too complicated to be regenerated in the same way that seastars' body parts can be.

A few optimistic souls say this might just be a temporary state of affairs. Sometime in the next few decades we may unlock the chemical communication secrets of pluripotent stem cells and set to work regrowing our own body parts. However, until that day comes, I wouldn’t get too close to any wood-chippers.