Social Media

In the past few months a group of ALS patients (PALS) and caregivers (CALS) have banded together via social media to support each other, spread awareness, educate themselves, and effect real change in their lives. This is more than blog posts and Facebook status updates but rather a concerted and united effort to fill some of the void in the research and treatment of their disease. Using email and messaging, individual projects have combined as a force-multiplier and are already beginning to see results. The ease of using and linking various social media technologies have allowed the infirm to reach out to and engage a global audience in a way and with an impact never before possible. They can do this because they are young, angry, and embrace technology to support and replace lost physical abilities. This movement represents a potential paradigm shift in the way ALS is perceived and dealt with. The list of projects includes (but is certainly not limited to) my project to draft Hugh Laurie to be an ALS spokesman, Thomas Ohlson's Petition to ALSA National, the remarkable and unprecedented ongoing serial documentary following Timothy Lafollette from diagnosis to current time, and the recent various and coordinated efforts to rescue a quadriplegic PALS from an abusive nursing home situation (in which this blog also participated). There are many other projects with various strategies, but all with the goal of increasing awareness, research funding, and support efforts. Where in the past these efforts would be singular, isolated, and have very limited impact, with the use of social media (Facebook, Twitter, blogs, online forums, email and messaging/chat systems) they are now being coordinated and their message distributed all over North America. As the number and scope of projects increase, there can only be a positive effect. If you have or know of a project to increase ALS awareness, please hook up with us via social media!

Wordsmith

Since I am on a vent (tube stuck through neck into trachea, below vocal cords) and can no longer talk, I must throw my voice to another object. I therefore create a new word describing this amazing feat: "Venterloquism" This makes me and other similarly entubed PALS (along with our brothers and sisters in high cervical injury) Venterloquists. This is not to be confused with Ventriloquism which involves the creepy practice of people with Dissociative Identity Disorder manually sodomizing puppets for the purpose of entertainment. Venterloquism involves any of several methods of overcoming a cruel obstacle to communication. Methods include the rudimentary Eyebrow Arch (induce your meatpuppet to say "yes" or "no"), The Ouiji (make your proxy point out letters and phrases on a board), and my personal favorite, The Hawking (making your words emanate from a nearby computer). Advanced and prepared Venterloquists can even use The Hawking to produce their actual voice for certain phrases! Venterloquism is a growing skill set among a diverse population of participants. Please support your local Venterloquist!

911

I need everyone reading these words to take a few minutes to read these words. This has nothing to do with politics. This is a genuine emergency call for another PALS in desperate need. If anyone is in the area I implore you to consider some volunteer work. Contact me for details if you are able to volunteer. This is shocking and wrong and should be criminal.

RoIP

Like VoIP (Voice over IP) for phones, the Internet also carries "Radio" over IP. I will be participating in an online radio show, The Global Voice with Susan Piontek. I will be joining ferocious advocate Michele Dupree of Carnival for PALS, Mike Miller, the founder of ROALS, and Mike Shannon of ALS-TDI. The show will air tomorrow, Wednesday, September 1, at 5pm PDT. This may be "today" for those of you who subscribe to this blog via email. The subject will, of course, be ALS and I will be providing my view of things from the perspective of a PALS. This show will actually be Part 2 of last week's show which ran out of time as the subject has so many facets. That show is archived online at this link. Because I am on a vent and can't speak, I have prepared responses to some questions which were provided in advance. My wife, Claire, will read them live and I will edit this post on Thursday to include them (as well as a direct link to the archive). Listen live and either call in with questions or type into the simultaneous web chat. Maybe you'll hear me do my Stephen Hawking impersonation! [edit] The archived version of Part Two can now be found here. My Q&A transcript follows below: Q: Tell us about yourself and how ALS has changed your life? A: At the time of diagnosis I was 36 years old, had a wonderful career in Information Technology and had just taken a position to manage the computer network infrastructure of the US research and development program for an automobile manufacturer. I had a little house on the shore where my wife and I could walk down the hill to celebrate our wedding anniversary by surfing together (also our first dating activity). I had everything I wanted and was extremely happy in my life. Then all of that was removed piece by piece. I am now quadriplegic, we are about to move to my parents' house, and I require a machine just to breathe. Fortunately the Internet is a great physical equalizer so I can continue my online life somewhat unchanged. Unfortunately, I now have plenty of time for Facebook. Q: What would you like people to know about ALS; the disease, the current research, the expense? A:Words will never be able to adequately express the pure horror that is ALS. You can feel pain but not move to avoid it. You can feel hunger and thirst but never consume to slake. Dignity is utterly destroyed. There is no other condition with the same combination of helplessness and misery. There is no risk factor or behavior which brings this curse, and not nearly enough is being done to end it. There are many fine people working to solve this but their work isn't supported enough and there aren't enough of them. PALS don't have time to wait. The technology is recently available to adequately study the problem so the only thing needed is money. As Dr. Stan Appel testified before Congress, "ALS isn't incurable, it's underfunded." The research is beginning to zero in on things that can make truly effective therapies and a few promising clinical trials are just starting or will soon. For the meantime, medicine has gotten quite good at dealing with the symptoms of ALS and Medicare pays for it. However, on the most crucial aspect only half measures are available. While ventilators and supplies are paid for, the people necessary to maintain the equipment, handle alarms, and assist with personal issues are not. Family members, when they exist, are destroyed from the combined physical and emotional strain. The cost for attendants is high and has bankrupted me. PALS can be productive in society with proper support and I am living proof. In addition to other activities I have begun to lobby ALSA to be more aggressive in public education and to persuade Congress to amend Medicare to pay for in-home vent care. Q: What can people do to help? A: The easiest way to help is to support an organization like TDI. But that is too passive. Our society likes to write a check, push a button, take a pill, then forget about the initial problem. That level of commitment doesn't cut it. In _addition_ to a financial contribution, more people need to follow the lead of the 3 Ms and agitate. Write a letter to ALSA demanding national television PSAs with a current A-list celebrity. Write a letter to your Congresscritter demanding changes to Medicare so PALS don't opt for death in the face of daunting costs (I have a year-long debate going with a friend who is facing ventilation). If you know of someone with ALS, keep that person's name in the local press. Write to the TV news networks demanding more coverage of this silent crisis. The more people who are aware of ALS, the more demand for a solution results in more action, more funding, and more participation from the industry. And use social media to reach out and coordinate activities. 10 voices are easy to ignore. 10,000 not so much. I and a group of PALS use social media every day to connect and coordinate. The services are free, very easy to set up, and have global reach. I have my blog and a Facebook page to recruit an A-list celebrity. If I can do this, someone with functional hands certainly can.

Salty Dog

As discussed in a previous post, immune modulation appears to be a promising pathway to attack ALS. Recently, a company called Neuraltus has commenced a Phase I clinical trial of a substance they code-named NP001. This substance also works as an immunomodulator by reverting immune system cells from hostile to nurturing. For some time, chronic inflammation has been recognized as an important factor in ALS (though the cause remains elusive) and many attempts have been made to control it. This appears to be another promising method. It can be deduced from the press release that NP001 manipulates the cytokines in the body which signal the various reactions to injury or infection. But what is NP001 and how does it work? Neuraltus isn't revealing the secret sauce so I went on a treasure hunt through PubMed. One of the chronologically earliest results of searching on the Neuraltus founder Michael McGrath reveals that he has been investigating immunomodulation since 2002 (actually earlier, but this study serves as a good starting point which will become clear later). In 2004 he co-authored another paper investigating the immunomodulatory effects of WF10. WF10 is interesting because it down-regulates pro-inflammatory cytokines by reacting with hemoproteins to form hypochlorous acid which then reacts with taurine to form TauCl which inhibits the inflammatory cytokines. WF10 seems to also have some drawbacks so another, "gentler", chlorine ion donor is probably desirable. In 2006 another paper was published, co-authored by Dr. McGrath and Dr. Robert G. Miller (the principle investigator in the NP001 trial) which investigated the role of defective macrophages in Sporadic ALS which expanded upon their 2005 paper. This research is doubly interesting as it looks directly at SALS as well as posits functional biomarkers which can be used to gauge drug efficacy instead of the clumsy ALSFRS (the NP001 trial lists this as a secondary outcome measure). A paper in 2009, again co-authored by Drs. McGrath and Miller, not only investigated immune activation in SALS but posits a cause. I hope to talk about that in future posts but for now I digress. With the evidence for immune system involvement in ALS and the evidence that a chlorite-based drug can neutralize some of the cytokines that promote inflammation, it seems to make sense to investigate whether such a drug can address the neuroinflammation of ALS. I have an unconfirmed report that sodium chlorite is the active ingredient in NP001 (the chlorine ion donor). Also, according to this 2006 patent issued to Dr. McGrath, TCDO (WF10) and sodium chlorite are both considered for ALS treatment in dose-dependent manner. I am intrigued and hopeful that this drug could have a positive impact in ALS. By reducing the amount of "attack" signals (cytokines), the "nurture" signals might help to end the damage caused by the neuroinflammation. Unfortunately my search for any of Neuraltus' preclinical (animal) research served a bagel so we have to wait for human results to evaluate beyond speculation. Of course, as always, remember that I am not a doctor or biochemist so take my words with a grain of salt (NaCl, sodium chloride, table salt.. get it? I apologize).

Shah Den Froi Duh

There is a game show on ABC I enjoy called Wipeout. This is because I enjoy seeing people with a full set of NMJs get pummeled by padded machinery. It is the ultimate in schadenfreude television!

Poor SOD

There has been a question whether SOD1 plays a part in sporadic ALS (SALS) as well as familial ALS (FALS), in which one of a large number of inherited defects in the SOD1 gene cause alterations (misfolding) of the SOD1 enzyme which it encodes. A recent study published in PLoS ONE suggests that misfolded SOD1 is present in all cases of ALS, not just in those involving genetic defect. Some previous studies have had similar results while others have not. Apparently this study used a fairly aggressive set of antibodies to detect inclusions (flaws) in the motor neurons which consisted of SOD1. Whether the misfolded SOD1 or the inclusions/aggregates that result are the cause of disease is still being questioned, although disease effects can be seen prior to visible aggregates forming. Two things about this study I found interesting: First, the study reported that the inclusions were found mostly in the axon hillock which makes me wonder if this can be related to the slowing of axonal transport which is a very early event in ALS. Second, if you look at the diagram in the SOD1 link above, you can see that it is a rather tight and highly complicated enzyme to fold. A mutation may make it more difficult or impossible for a lysosome to break down. Lysosomes are rather important cellular components. The subject study indicates that the misfolded SOD1 found in the motor neurons co-localized with lysosomes, suggesting that the lysosomes were choking on the mutant enzymes. Lysosomal dysfunction has already been linked to several diseases, including neurological. It is known that lysosomal function degrades with age, and ALS is an age-related disease (both SALS and FALS begin after decades of otherwise normal life). At least one study is being conducted, attempting to address ALS by means of increasing lysosomal function. Of course, this assumes a "neurocentric" view of the disease, where the pathogenesis is in the neuron itself. Recent research suggests this may not be the case, and that some upstream event triggers the cascade that leads to distress and death of the motor neurons. It is this "missing link" that continues to confound researchers.