Pet The Petition

A few months ago, I posted about publishing companies trying to charge for access to research studies paid for by taxpayers. Today my friends at The Doctor Weighs In posted about a way for each of us to really make a difference in this fight.

The White House has an online petition system where citizens can weigh in on issues before the President. If the petition gets 25,000 "signatures" within 30 days of it being created, it will be presented to the President where it must become part of the policy discussion. This is a great way for We, The People, to address and direct our government (especially in these times of corporate-captured government).

There is a petition currently in circulation to demand that scientific research paid for with taxpayer dollars remain freely accessible to anyone wishing to read it. The current signature count is just shy of 16,400 and I strongly urge my readers to sign and share this petition by email and/or social media. Working together we can ensure our intellectual property isn't stolen and we are then charged for its return by the very thieves who stole it.

All Alone

It's the middle of ALS Awareness Month. Individuals have been doing an excellent job of pushing awareness in their local circles. This includes pet groomers holding awareness and fundraising events,

R U A WARE?

It's ALS Awareness Month. As per usual, certain advocacy agencies are content with passive website pages and extolling their constituents to do the heavy lifting of spreading the word (a practice that has dramatic fall-off beyond the tiny individual circles of family and close friends). The agencies bleed enough contributions from the constituency to pay salaries and provide token services (with no consistency between Chapters). Meanwhile, The general public is still unaware and uninformed about the deadly lottery that is ALS.

Up until very recently, ALS was a disease of silence. As Person(s) with ALS (PALS) progressed, they lost their abilities to communicate and mingle in their communities. Very quickly they were shut away in homes or hospitals to die in mute angst with a capable mind trapped in an inert body.

With the advent of social media, as well as the technology of mobile computers with eye-tracking input systems and text-to-speech synthesis, PALS are able to compete on an even footing in cyberspace with more physically capable people. Many of these PALS are in serious medical conditions such as near total paralysis with some on mechanical ventilation via tracheotomy. As the astrophysicist and PALS Stephen Hawking said, "My body may be crippled but my mind is free." Tech-savvy PALS are able to use combinations of technology to dramatically increase their standard of living, to contribute to research about the disease, and even band together to lobby government to speed up access to promising pharmaceuticals. As wonderfully-explained in a recent forbes.com article, "Technology is the cure" (thanks to Steve Saling for coining that phrase).

On a personal note, technology is saving my life. Many years ago my father was in the US Air Force flying support missions for the Apollo moon flights. On occasion I would be in ARIA control watching technicians tending to walls of huge computers. I thought that was the neatest thing ever. Years later, I was blessed to turn a childhood hobby (began when I commandeered my dad's IBM PC in 1980) into my career, and I now have in front of me more computing power than all the Apollo vehicles combined.

When I was diagnosed, I knew that my ability to communicate was going to disappear. Knowing that hands-free computer technology existed, and already having a long-term presence in "cyberspace", I knew that I would be able to be social and productive as my physical ability declined. This was paramount in my decision to accept mechanical ventilation. Without the ability for my mind to escape my physical confinement, I would have years ago allowed myself to succumb to ALS. Instead I have remained active and have had the extraordinary privilege to meet and participate in the global ALS Community.

Unsatisfied with the level of advocacy and awareness generated by organizations with that as their claimed mission, PALS in the global ALS Community are taking it upon themselves to increase awareness and advocacy, and are placing pressure on those representative organizations to change old operating procedures. Other organizations representing other medical conditions are very vocal and aggressive in public awareness (the foundation of funding and national priority for research) and this new group of PALS demand commensurate action from the organizations representing them. The new computer technologies, mobile devices with apps, and ubiquitous connection to the Internet and social media allows PALS to congregate, exchange ideas, and mobilize. No longer are they shut away and forgotten.

This month, are aware or are you just a ware for fundraising that does little?

Lack of Inhibition

ALS is frequently regarded as a disease just of the motor cortex, but degeneration is also seen presymptomatically in other cortical areas with functional connectivity to the motor cortex. It seems that the areas of highest functional connectivity overlapped with areas of highest damage. This is theorized by researchers to be due to a loss of certain neurons which serve to modulate the activity of other neurons ("inhibitory neurons") in a process called "cortical hyperexcitability". In a recent study, researchers measured levels of GABA to support the evidence of this process in PALS. In a similar study published 04-18-2012, GABA was also found decreased in the motor cortex of PALS vs healthy control subjects.
Emerging evidence in another neurodegenerative disease, Alzheimer's Disease (AD), indicates a similar functional connectivity method of progression. In another more recent study this was also linked to a similar-sounding process called "network hypersynchrony".

Under Press-Sure

Over the past two weeks ALS has gotten some much-needed national coverage, first from the Wall Street Journal followed shortly by ABC News. I also just completed the first round of questions for an article due to appear in July in the-scientist.com. More opportunities seem to be materializing and I will do my best to keep the momentum going to keep the message of ALS in front of the public. I would like to call upon everyone to contact their local press, mention the WSJ and ABC News articles, and tell them YOUR stories. If you think it would help to mention a relationship to me, do so and I will back you.

There were a few points in the articles that I wanted to clarify:

• I did not design the computer I use. It is a TabletKiosk Sahara Slate PC i440T with a Point Grey Flea-2 CCD camera with an infrared light and lense. The system uses the ERICA software made by Eye Response Technologies (since purchased by DynaVox). The only part of the computer I modified was my work environment and I installed certain programs and utilities which I use. I did help design the overhead mount which slides along the overhead track I use for my lift.
• NP001 is indeed sodium chlorite, but when ingested orally the acid in the stomach breaks down most of it. The most optimistic data I have seen (based on rats exposed to it in drinking water) is a maximum 30% reaching the bloodstream. I would expect that to be less, and to be variable, in most people.
• Because NP001 is already in clinical trial, I arranged the project more as an "early access" model with data-keeping as secondary.
• I have three criteria for any such projects:
  • drug must be relatively safe
  • drug must be inexpensive
  • drug must be legal to obtain

It's very important to me that I don't recklessly put other PALS in physical, financial, or legal jeopardy with any project. My intention is to help not harm. We all already have enough problems to deal with.

Old Tricks

Something very intriguing came in over the weekend from PLoSONE. It was a study comparing neuromuscular junctions between age and ALS. It turns out that the same muscles susceptible to denervation in ALS are likewise susceptible to denervation with age. Autonomic muscles (those that act without your conscious input) and muscles innervated directly from the brain (eg your eyes and certain facial muscles) are extraordinarily resistant to age- and ALS-related denervation. Something that struck me was the finding that TDP43 was mislocalized in aged motor neurons very similarly to ALS motor neurons. TDP43 is normally found in the nucleus but in ALS it is found in the cytoplasm where it is cleaved by caspases and a 25 kilodalton fragment aggregates in a form that apparently gains a toxic function.

TDP43 mislocalization has also been found by the symptomatic phase in the SOD1 mouse model (although earlier and more recent reports are somewhat contradictory on this point). Another protein found upregulated in the SOD1 mouse is CRMP4a, a subprotien of the CRMP family. CRMP4 is normally involved in learning, neurite outgrowth, and building functional circuitry within the brain. However, the Duplan, et al., 2010 study referenced above found upregulation or overexpression of CRMP4a is deadly specific to motor neurons. In the subject study of this post, Valdez, et al., 2012, CRMP4a was also found upregulated in the same types of motor neurons of normally-aged mice as those which degenerate in ALS mice. CRMPs are known to change due to age.

Inflammation is present in all neurodegenerative diseases. One of the primary drivers of ALS is thought to be neuroinflammation. Multiple animal models of ALS, including data in humans, show neuroinflammation. As the subject study shows, TDP43 and CRMP4 is upregulated in both aging and ALS. Taking one step further, aging and ALS have another thing in common: Inflammation.

Growth Potential

Two new studies came out that I found rather interesting. The ability to transfer into humans is years off but the progress is still impressive. First up, a team at the University of Toronto developed a new technique to expand stem cells at industrial capacity. Second, Children's Hospital of Philadelphia generated a new human stem cell type called an "endodermal precursor". If the new stem cell technique can also be used to generate ectodermal precursors, it could be a major advancement in regenerative therapy for ALS. Many additional steps would still be necessary but mass-production of teratoma-free cells would be an important contribution.