Wednesday, 3 September 2014

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.


2 comments:

Eric said...

One interesting note: it's almost certainly not damage from the extra free radicals that causes ALS. Mice without any SOD1 don't live as long as mice with normal SOD1, but they don't develop ALS symptoms. So it's likely the misfolded SOD1 is doing something else that is messing with neuron function.

Sketchy Science said...

That's really interesting. Hopefully the influx of money can help them figure out what that something is