Often Awesome

Today the ALS Community lost yet another member. Tim LaFollette, Mr. Often Awesome, has returned Home. My heart is with his wife Kaylan. While I initially hid my condition for over a year, Tim had the foresight and steel balls to create the Often Awesome video documentary series so that the entire world can see his decline as he battled this disease from start to finish. This is "Tuesdays With Morrie" on steroids -- a very intimate and detailed look into the horror and hope that is ALS. Not only did it show the effect on a young man cut down in the beginning of his prime, but it showed the devastating effect on family, friends, and community. One person may carry the disease, but many suffer irreversible collateral damage. People have told me how brave I am. However, compared to Tim, I merely dabble in ALS. He had the A4V inherited version, the worst and most aggressive possible. Whenever I would feel down about my situation, I would think about Tim and how he dealt with even worse with a fortitude and grace I cannot contemplate. I would like to thank him for unknowingly lending me some of his strength. I never met Tim personally, only having worked with him over Facebook on awareness and advocacy projects. When I heard the news this morning I shed exactly one tear. I then decided to more properly honor his memory by continuing to live with ALS as he did, on my own terms. I also intend to honor Tim by winning my battle and, like he did, help others win theirs. Fuck ALS.

Common Cause?

A sensational bit of news has begun spreading across the ALS Community: A common cause for all forms of ALS has been found!

But has it? Certainly it is a common process but is it really the cause?

The process involved is autophagy. One of the important jobs of autophagy is to break down and recycle misfolded (improperly constructed) proteins marked by another protein called ubiquitin. A proteasome then breaks down the protein into amino acids which are then used to build new proteins It's like tearing a house apart, timber by timber, and reconstructing another from the material. If this process is interrupted or incomplete then you have a pile of junk left laying around which is thought to impede the efficient operation of the cell. An example of this is the amyloid plaques that are thought to cause Alzheimer's. However, removal of those plaques did not affect disease progression.

ALS is now strongly considered to be a "non-cell-autonomous" disease. This means that something outside the cell is causing the disease. Some of the most persuasive evidence for this is a recent study involving cells known as astrocytes become toxic to the motor neurons. This happens in both the inherited form (familial or FALS) and the more common sporadic form (SALS). Previous readers will know about my interest in current research regarding neuroinflammation as a primary cause of ALS and other neurodegenerative disease. This is also a common cause from a variety of triggers. It is, however, upstream of the "cause" identified in the recent news.

The calcium influx from the excitotoxicity created by neuroinflammation damages the mitochondria. In fact, this is a primary event. It is known that the motor neurons "die-back" along the axon, and that mitochondria motility down the axon is one of the first problems in ALS and neuroinflammation models. Once the mitochondria are damaged and cannot be repaired/replaced, pretty much all bets are off inside the cell. The cell becomes starved for energy, the cellular machinery (such as proteasomes) begins to fail, and the mitochondria start producing apoptotic factors which leads to cell death. Normally this wouldn't be a problem as many of the cells in the human body die and are simply replaced (even brain cells). However, the motor neurons you are born with are the very same motor neurons you die with.

I therefore posit that this "common cause of ALS" is too downstream of the actual cause for treatment based solely on it to be effective in and of itself. It's like trying to stop a waterfall at the edge of the cliff rather than building a dam in the stream a mile further behind. I do believe that although this may not lead directly to a single effective treatment, it would nearly certainly be an important part of a "cocktail therapy". The major positive I take away from this is that it answers the question whether the SOD1 model is applicable to all forms of ALS.

Chatterbug

Since I lost the ability to travel and talk, I use Instant Messaging to keep in touch with family and friends all over the world. Everybody seems to have their favorite client, be it MSN, Yahoo, AIM, or Google. Rather than try to force everyone to switch to a client program of my choosing, I installed all of the various programs and created accounts (I did force some to stop using Facebook chat because it doesn't play nicely with my system). This was fine and dandy, but now my boot load time was obnoxiously long and my computer's RAM was getting low, leading to performance issues. Luckily I had bumped my system up to 4GB in anticipation of my higher-than-normal demands. This led me to search for an alternative, where I could combine most or all of my clients into one ("One client to rule them all, one client to find them..."). Prior to disease, most all my computer systems in the house ran Linux. On my personal laptop I used a program called Pidgin which talked to all the major IM services. The Windows port I found a little lacking and probably not a great fit for most users. A friend then suggested Trillian. I installed it, ran through the setup to fill in the login information for my various IM accounts, and launched the application. I was impressed with the sleek interface. All chat sessions are in one tabbed window. The settings are easy to use and customize. And my RAM usage dropped by about half a GB! Trillian doesn't support all of the functionality of the native clients such as video/audio chat and sometimes the file transfer isn't available, but for regular text chat (including the overly-cute emoticons) it works great. If I need the other functions I just pop up the native client and close it when I'm done. To save boot time and RAM I disabled the natives from loading at boot. It also supports a Facebook connection but I found the newsfeed to be annoying; I prefer to leave Facebook on the web browser where it belongs. I would also caution about security: Your IM logins and conversations are not encrypted or secure and possibly subject to inspection by 3rd parties (also quite possible on the natives), so be aware that transmitting sensitive information over this is not advised. If you are a chatterbug like me, I recommend using Trillian on your AAC computer. I would even recommend it for non-disabled people.