Tag Archives: technology

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Spicy News

Audio Podcast (192kbps MP3)
(video at bottom of text)

Welcome back to the Cripple Command Center or C-to-the-3 podcast on ericvalor.org. My name is Eric Valor and I will be your host and head nerd in charge. In this episode I will report on a recent webinar given by CIRM, the California Institute of Regenerative Medicine, and a particular clinical trial discussed therein. I will also report on a new potential treatment target for ALS found using CRISPR, a new proposed treatment for SOD1-linked ALS, a new open-label trial for a form of curcumin, and a new stem cell model to assess possible treatments for neurodegenerative diseases such as ALS.

The first item up for bids is the new CRISPR study. Researchers at Stanford University have used CRISPR/Cas9 gene editing technology to gain insight into the genetic basis of ALS. The team, led by Doctor Aaron Gitler, used the technology to sift through the entire human genome to find genes that help neurons defend against toxic protein aggregation. In ALS it is known that proteins inside the motor neurons clump together, depriving the cell of the beneficial function of these proteins as well as choking the machinery which normally breaks down malformed or deficient proteins for recycling by the cell. The Stanford team used CRISPR to sequentially alter genes which either help cells cope with protein aggregation or enhance the toxicity. They ceased the function of each gene one by one in what’s called a “genetic knock-out” and evaluated the effect. That way they can identity potential drug targets for future therapies. You can read more about this in the Stanford News Center website. You can read the paper in Nature Genetics.

Our next item is the CIRM webinar and the upcoming clinical trial described therein. The webinar was held on Facebook. It was an “Ask The Experts” format where information is presented and then questions are asked by people watching the webinar online. The presentation was made by Doctors Clive Svendsen, Bob Baloh, and Ralph Kern. First, a little information was shared first about the NurOwn therapy in trial by Brainstorm. The Phase 3 trial is enrolling 300 people with enrollment expected to finish by early 2019. The protocol is repeat injections of the person’s own mesenchymal stromal cells which reduce local inflammation and secrete trophic factors which help the motor neurons heal and grow.

The juiciest part of the webinar was the presentation of the new Phase 1 clinical trial being prepared by Cedars-Sinai in Los Angeles. This trial is similar to the old Neuralstem trial using human fetal brain-derived neural progenitors which are multi-potent stem cells which can only become cells of neural lineage (neurons, astrocytes, microglia, etc.). In contrast to the Neuralstem product where the cells mostly became interneurons these cells become astrocytes which would replace the native astrocytes which become toxic in ALS. The cells are transduced using GDNF (glial-derived neurotrophic factor).

Cedars also uses a new method called “chopping” (which when you read the paper on the method should really be called “slicing”) to expand the cell line into a pharmaceutically-relevant number. A clump of neural cells called a neurosphere is repeatedly sliced up and the parts allowed to expand. The usual method is to break apart the neurosphere by hand and individually plate the cells. Chopping is much faster and increases yield by allowing the cells to be cultured in 3D rather than in 2D. This means the cells have more contact with others which promotes health and growth. Instead of having cells just on the left and right and on top and bottom, they also have cells above and below. Like penguins grouping together tightly in a snowstorm the cells fare much better in a 3D arrangement as in the body. Like the Neuralstem trial the Cedars trial uses a laminectomy to inject the cells into the spine but uses a new rig which is significantly less invasive. The patients undergo a year of immunosuppression to ensure the body doesn’t reject the implants. After that the cells are expected to survive for life.

Next up is the new clinical trial for the spice curcumin being put together by my friend and ALS Untangled colleague Doctor Richard Bedlack. The trial is called ROAR for Replication Of ALS Reversals. ROAR is open-label with no placebo and is designed to have faster enrollment with much better retention, and wide inclusion criteria like no 2-year cutoff or many of the other exclusions found in usual trials. That’s not to say that the usual trial design is “bad” but ROAR is looking for a huge unmistakable signal: A reversal of ALS such as regaining use of limbs or getting out of a wheelchair (the latter being a more extreme example). The trial will also have few/no in-person visits. ROAR will use a particular product called Theracumin which is a highly concentrated form of curcumin which is readily absorbed, properly metabolized, and is well-tolerated even in high doses. Trial participation for each person is 6 months. The real-time results will be available on Patients Like Me and the full protocol will be made available on www.alsreversals.org should anyone not in the trial want to follow along.

Why curcumin? Because it’s generally regarded as safe and is inexpensive to obtain. There are some 12,000 published papers studying curcumin’s effects. Curcumin has powerful antioxidant effects, can reduce protein aggregation in cells, can induce beneficial gene activation, and can alter the gut microbiome, the vast population of bacteria in the stomach and intestines, in ways that are beneficial to health including the brain and nervous system (seriously!). In mouse neuroblastoma cells transfected with mutant TDP43, curcumin improved excitotoxicity, improvd mitochondrial function, and reduced oxidative stress and protein aggregation. Unfortunately these studies have not been independently replicated. You can learn more about curcumin and prior data as relates to ALS in the ALS Untangled report on the subject and by watching the video presentation Dr. Bedlack gave on the ROAR trial.

Alrighty, what do we have next? Ah, yes, the new stem cell model meant to assess potential treatments for neurodegenerative diseases like ALS. The model is specifically for Alexander disease (AxD) because of its relatively simple pathology. But it’s relevant to Alzheimer’s, Parkinson’s, and ALS because it focuses in on malfunctioning astrocytes. In AxD, astrocytes with a mutation in glial fibrillary acidic protein (GFAP) secrete a protein called CHI3L1, a marker of neuroinflammation that suppresses neural development-related processes, including myelination. The CHI3L1 suppresses cells that are precursors to oligodendrocytes, the cells that wrap the neural axons in a fatty substance called myelin. Myelin acts like the plastic insulation of electrical wires and performs much the same function. The idea is that by understanding more about astrocytes that would reveal clues about how to treat diseases like Alzheimer’s and ALS.

And that’s all for this episode of the C-to-the-Three Podcast on ericvalor.org. I am, and always will be, Eric Valor. Until next time, breathe easy.

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RTT Blues

Audio Podcast (192kbps MP3)
(video at bottom of text)

Hello and welcome back to the Cripple Command Center podcast. My name is Eric Valor and I will be your host for this episode. The Cripple Command Center, or C-to-the-3 (C^3), is where I live, also called The Blue Room. It’s where I make and produce this podcast. It has been a while since I published a podcast. I have had some personal and health issues including one that landed me in the hospital. Afterward I was quite exhausted and needed time to rest and recover. Turns out staying in the hospital is not good for you.

So, now to the news. First, I am pleased to announce that I have self-published a book of my own poetry titled “Hamachi Eyes”,written over the past few decades. It’s on my website under the About Me tab. I also have a bunch of my original food recipes under the same tab so have a look if you’re into the culinary arts. Ironic that I really got into cooking after I could no longer eat. Anyway, the book is about 89 pages of a journey through my interpretations of various experiences.

I think the first poem I ever wrote was when I was around 9 or 10 and I remember it being well received. That’s when I first felt I had a little talent in writing. Unfortunately I don’t have a copy so it’s not included in the book. You can freely download a copy in either PDF, Amazon Kindle, or generic e-book reader format. I hope you download a copy and enjoy it. Since publication I have had selections published in the New England Review of Books. You can also listen to an audio version of the interview I did in support or read it on the NEROB website.

Next, many of you have heard that Brainstorm will not be releasing its proposed therapy for ALS under the recently enacted Right To Try law also called RTT. I have been against RTT since it was first proposed because I knew that it would be ineffective in anything except reducing the ability of the Food and Drug Administration to properly oversee the safety of the drugs produced for sale by pharmaceutical companies. In fact, RTT is no different from the long-existing Expanded Access Program that the FDA created at the turn of the 1990s in response to the HIV/AIDS crisis.

The only difference between RTT and EAP is that the FDA now has a little less authority to halt experimental drugs and therapies that show issues in patients who obtain them outside of official clinical trials. Pharmaceutical companies have no compulsion to provide their products outside of trial and if they do, the patients obtaining them will be subject to large personal cost. And, according to the history of drugs and therapies in trial for life-threatening diseases for which no truly effective treatment options exist, the treatment probably won’t be effective.

What has happened is that patients, specifically Person(s) with ALS or PALS, have been used by the GOP to advance its decades-long deregulation agenda. I warned of this when it was being presented by PALS and we are seeing now that RTT won’t be effective. The Brainstorm product, Nurown, was the original target of RTT and it will not be provided.

Last, a bit of advice. If you tell a PALS that you love him or her, you better damn well mean it. We already have enough trauma to deal with than to have a mate vacillate and/or suddenly vanish. Nothing can deal a worse blow to the already fragile grasp on hope most PALS have. If you don’t mean it or aren’t fully committed then stay silent. False hope is worse than no hope.

Thanks for tuning in to the C-to-the-3 (C^3) podcast on ericvalor.org. Sorry it was such a short one. I am and ever will be Eric N. Valor, and until next time, breathe easy.

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Awful Truth: What’s Old Is New – Again

ALS - The Awful Truth

(video at the bottom of text)

I am re-releasing an older video I did with a new somewhat tighter look and some upgraded language (words I never liked when I originally released it). Essentially, nothing has changed in 6 years since 2011 to 2017. Radicava was approved for use in the USA, but it only works in very recently diagnosed patients and only for about a year. I classify it with Rilutek as a medication with a rather modest effectiveness. No truly effective and approved treatment exists yet for ALS.

And PALS are still being forced to make the terrifying and grisly choice between bankrupting their families merely for the privilege of living or just accepting a rapidly accelerated death where one morning their children or spouses would find them cold, pale, and never to wake again. Everything is covered by Medicare except the people required for being close by for the inevitable situation of something happening with the ventilator – normal moisture or mucus buildup, the air hose popping off, or something drastic going wrong with the machine – any of which mean death in minutes. Immediate family CANNOT be caregivers because the stress is just too great already. The health consequences would splinter a family at a time when being close together is the most important.

It is despicable that even when new treatment options which promise significant extension of life for PALS that they may be unable to enjoy that gift with their families.

Please enjoy my renewed video message.

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MAGIC Mitochondria (and more)

Audio Podcast (192kbps MP3 download)
(video at bottom of text)

Hello and welcome back to my podcast.

My name is Eric Valor and today I have a few different subjects to cover. I will cover the new ALS treatment recently approved by the FDA, the latest message from Hope Now For ALS, MAGIC in yeast cells, and trouble for stem cell therapies.

But first, I would like to make a personal announcement. Some of you may already know this, but I was recently accepted to the Academy of Neurology as a researcher. It’s not a huge deal but it’s nevertheless something I am proud to have on my CV.

ENV AAN Cert

Now, to business. My first item on the board is the first drug to be approved for ALS in 22 years.

In May of 2017, the FDA approved edaravone, also called Radicut or Radicava, for use in the United States. Edaravone was developed and originally approved for use in Japan in 2001 for protection from the effects of a type of stroke. Its MOA, or method of action, is as a scavenger of free radicals. These molecules have an unpaired electron in one of their atoms, making them extremely reactive with other molecules. The radicals at subject are called reactive oxygen species or ROS, produced as a byproduct of the mitochondria creating energy for the motor neurons. These molecules, when not properly controlled, cause significant damage to cellular structures. There have been many attempts to eliminate these ROSs as a treatment for ALS, but all previous attempts have failed.

There are some side effects resembling allergic reactions, from redness and itching up to anaphylaxis, which requires immediate emergency medical assistance or the person can perish). The incidence of serious adverse effects (SAEs) was low, with the most common, dysphagia or difficulty swallowing, occurring in 12% of patients. Milder adverse events occurred at the same rate as placebo.

Edaravone Adverse Events

The dosing regimen is 14 days of one infusion per day of 100 milliliters administered over one hour followed by 14 days with no infusions. Subsequent cycles are 10 days of infusions followed by 14 days without. Edaravone showed up to 33% slower progression in patients who were fewer than 2 years post-diagnosis, were still ambulatory, and could still feed, dress, and bathe themselves. Three out of four clinical trials of edaravone for ALS failed to meet clinical endpoints, but the fourth, when restricted to the PALS described previously, met its endpoints. What that means is that it seems effective only in people very early on in progression.

The second item on the agenda is the recent update which Hope NOW for ALS posted about its activity. On May 10, 2017, HNFA released a statement describing their May 1, 2017 meeting with key officials at FDA CDER. The statement also mentioned the approval of Radicava and how it is the first drug approved to treat ALS in 22 years. The main point of the HNFA statement was to indicate willingness by the FDA to consider updated clinical trial methods to make clinical trials more accurate and humane. It’s a hopeful message and indicates, along with the new approval of a treatment for ALS, that the FDA may be really changing how it sees and deals with life-threatening or fatal conditions.

ALZ Forum Logo

Third, the ALZ Forum has a nice article on mitochondria making MAGIC. In a study published in the March 1st edition of Nature, a team from Johns Hopkins University describe mitochondria in yeast cells untangling misfolded cellular proteins before tearing them apart for recycling the components. The process was termed “mitochondria as guardian in cytosol” or MAGIC. Aggregated or misfolded proteins which become tangled in each other are known to be torn apart in cellular machinery called proteasomes. Without mechanisms for breaking down these aggregated proteins they would clog the entire cell like the white of a boiled egg. You can see the same process happen as you fry your breakfast in the morning. That would be very bad for the cell and ultimately us.

In MAGIC, these same aggregated proteins are imported into the intermembrane area, a small space between the outer and inner membranes of the mitochondria. There the proteins are untangled from each other, then passed into the inner mitochondria where the individual proteins are chopped up. When heat shock proteins in the cytosol of the cell aren’t working properly this puts more stress on the mitochondria which are already very hard at work creating energy for the neuron. Think of it like hauling a heavy trailer up a mountain road in your car. Your engine strains under the load, getting hotter and pumping more smoke out of the tailpipe. The “smoke” from the mitochondria is the ROSs. The authors further reported that this process also happens in human cells. If those holds true then it would tie together two critical factors of neurodegenerative disease: protein aggregation and mitochondrial dysfunction. That’s would be an important finding as it would further elucidate the mystery of ALS, Alzheimer’s, and Parkinson’s.

In another story, again from the ALZ Forum, it appears that significant efficacy differences exist between clinical-grade stem cell lines and their research-grade counterparts. The differences may explain why some clinical trials fail. Two studies in the February 14 edition of Stem Cell Reports (study 1 and study 2) suggest that the outcomes could have been anticipated if the production lines were animal-tested the same way as in preclinical studies. The two subject studies looked at the unsuccessful trials by StemCells Inc. of spinal injury treatment using neural precursor cells. The company reported that the cells remyelination and motor recovery in mice with spinal injury.

But in two different trials with the same cells expanded using the Good Manufacturing Process (GMP) standard, required for production for use in humans, the cells failed to demonstrate efficacy. When the same lines were later tested in mice for the subject studies, they matured at about half the rate as the research-grade cells and largely remained as undifferentiated clumps. In one study about 4 percent of the grafted cells continued to divide and in some cases extended neurites into the surrounding tissue. Obviously injecting undifferentiated stem cells is a very bad idea and no two stem cell lines are identical. Together these studies provide strong evidence for preclinical testing of clinical-grade cells prior to use in humans.

Finally, another announcement: Beginning with this podcast (and retroactively back to the prior podcast) the video portion will be included at the bottom of the transcript. This will make viewing easier for my blog readers.

Thank you for reading and/or viewing. Leave a comment with your thoughts or any questions, and subscribe to get a notice in your email whenever a new episode is published. Until then, keep breathing easy!

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Cyborg With ALS (podcast)

New Blog Format!

Folks Logo

Audio Podcast (192kbps MP3)
(video at bottom)

Hello to my readers, and now listeners. Welcome to my new blog format where I will post the same text and web hyperlinks as always, but now there will be an audio podcast version on my Youtube channel in the new Podcast List. My electronic avatar, which I specifically created to look like me, will “read” the podcast and a link to it will precede the corresponding post. My channel also has various videos related to ALS and a few personal videos from my past. I will also have a lower-bitrate sound file available as a download link on each blog post. My hope is that this format will make my blog easier for people to enjoy. Everyone now can listen to my posts and then later check out the text version and follow the embedded links to learn more.

This post is to announce my latest interview with a new lifestyle magazine called “Folks”. It’s a publication by PillPack, a full-service pharmacy which separates medication into individual doses. This is pretty handy for people who regularly take medication and may have difficulty with prescription adherence, and institutions like nursing homes and hospitals. The publication was launched about 9 months ago and features people living with various medical conditions, refusing to be defined by that condition. I guess that would include me.

I had the good fortune to be contacted by Josh Andrew. He is one of the writers for Folks and he had heard my recent interview by Reply All, a podcast by Gimlet Media. Our interview was conducted over email. Unlike the podcast, I did not need to also send sound files. The link to the Folks article is in the text version of this blog post. Josh was kind enough to assist me with this podcast by answering a few questions about Folks and how they found me, and how the interview was done. The questions I asked were:

  1. Please describe what Folks Magazine is and what it’s all about.
  2. Please describe how you found me and why my story was interesting to Folks Magazine.
  3. What was the interview by email like?
  4. Have you ever done this before?

His answers are in the podcast.

Thanks for listening and/or viewing. Please leave a comment on this blog post and let me know what you think of the new format.

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Cyborg Is As Cyborg Does – Reply All Interview

World’s First Fully-Functional Cyborg

Reply All Cyborg

I am the world’s first fully-functional cyborg! Need proof? My part in this Reply All podcast starts at 16:35.

This interview took place over about 3 weeks including one live telephone call and approximately 40 questions over email to which I replied both with text and individual MP3 files of the audio of my computer speaking each answer. It was a rather interesting experience and one that would certainly come in handy for any future interviews. Sruthi Pinnamaneni and Rick Kwan did a great job of stitching all of the questions and answers together to make a single coherent interview.

My desire was to demonstrate that life goes on after diagnosis and that there is still PLENTY that someone can still do despite full paralysis and being dependent on a ventilator. Hopefully other more newly-diagnosed PALS listening to the podcast can take a little inspiration to keep living and contributing your individual wonderful gifts to the world. Together, our voices are amplified and we can create the change we want to happen in the world.

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Reply All – ALS Reversals

Reply All Podcast – The Reversal

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As many of you may know, Dr. Richard Bedlack has been investigating a very rare phenomenon known as “ALS Reversal” where the normally inevitably fatal disease can stop progressing and even where the patient recovers slightly or nearly fully. Over the past few months Dr. Bedlack has been interviewed for a podcast called “Reply All” (I know the timing because I was also being interviewed for supporting material). The podcast is worth a listen, and you can get read the transcript at the Reply All website.

This is more good exposure for ALS awareness. Thanks to Dr. Bedlack and to Reply All for a great story.

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Quora Top Writer Of 2017!

WOW! – Quora Top Writer Of 2017!

Quora-Logo

I just received an email today notifying me that I have been named a Quora Top Writer Of 2017! My contributions are tightly focused in the topic of Amyotrophic Lateral Sclerosis (which I created on Quora) with some attention in the broader topic of Neurodegenerative Diseases, along with a few answers in the topics Science, Physicists, and Stephen Hawking (to give a long-term patient’s perspective on some questions asked about the Professor, including one asking how he fathered children where my answer has 1.4 million views and over 20,000 up-votes – the Quora equivalent of a Like). I have to thank my friend Laura Copeland for introducing me to and getting me involved at Quora. Laura and I met in 2011 when she interviewed me for a story in my local newspaper. She and I remained friends ever since.

Quora is probably the best place to go for answers to questions about anything from science to global social issues and politics to personal hobby interest (maybe I should start a Surfing topic..?). It’s a highly erudite place, especially for a social media site and has astonishingly remained so for many years. Quora is a place where trolls are not tolerated and from which is almost totally free.

I am quite flattered to receive this distinction and am happy that my contributions have been deemed useful for the many people who have read my answers and those who have engaged in enlightening discussions after. It’s been a wonderful experience so far, where I have been able to definitely expand global public awareness of ALS/MND is a positive and engaging way. I am thankful for the opportunity and for the response. I look forward to many more years of engagement and enlightenment.

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Reddit AMA Guest Appearance

Reddit Tag-Along

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On Friday, November 18, 2016, I participated in a Reddit AMA as a co-guest in support of my friend, Jef Akst. Earlier this year she published a book titled Personal Trials: How Terminally Ill ALS Patients Took Medical Treatment Into Their Own Hands (available on amazon.com in both Kindle and paperback) about the Oral Sodium Chlorite Project I created along with Rob Tison and Ben Harris, and our journey through the DIY drug experience. Reddit asked her to do an AMA about the book and she asked me to tag along for the session to give the ALS patient perspective and as one of the subjects of the book.

It was my first time ever doing this and it was exhilarating. For two hours, Jef and I were furiously typing away trying to keep up with the deluge of questions. In fact, I am still going back and answering late questions right now. At first I was a little nervous about facing a bunch of trolls and kooks, as the Internet appears full of these days. But the questions were all quality and reflected a desire to actually learn something about the subject.

I am grateful to Jef for writing the book, telling the story of patients driven to find their own solutions to untreatable diseases. And I am extremely grateful to Reddit for giving us this opportunity to share a taste of the experience with others who may have never previously heard of ALS before today. And thank you again, Jef, for inviting me to help her tell the story.

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Guest Blog: Me!

SRG Research News – First A Little Background

As most of you know, I started SciOpen Research Group as a way for me to be able to fire actual bullets in the battle against ALS (well, actually metaphorical, but you get the idea). Our first project failed to extend life in the classic ALS mouse model so we retained the money raised to conduct the planned second part of that experiment. We had another project already in the research pipeline waiting to take the next step in development. For two years SRG was working on creating a novel molecule which would treat the desired pathway without becoming toxic like the reference molecule does at therapeutic doses. Suddenly we had the opportunity to collaborate with researchers already investigating the same pathway, albeit in different conditions (watch the video announcement), with their own library of candidate molecules.

Our collaboration’s first phase is to create a novel transgenic mouse species which represents a 100% drug efficacy in order to be a proof of concept. The project should run through the last half of 2016. As you will see below, a study was recently published which shows that SRG is definitely onto something. Our target protein is significantly elevated in human patients, and that targeting it brings positive results. The study is great indirect support of our project’s goal.

And now, the guest blog featuring myself!

Good News For Our Latest Project!

A recent report published in Science magazine strongly suggests that SciOpen Research Group is onto something with its currently ongoing study of necroptosis in ALS. Necroptosis is a “cousin” of apoptosis. In contrast to apoptosis, which happens regularly in the body, necroptosis is a form of programmed cell death which happens under inflammatory conditions and in which the components of the dead cell spill into the extracellular space. The spilling of the cellular components trigger a response in which immune cells are recruited to the area. Necroptosis is known to be a driver of both genetic ALS and sporadic ALS.

The subject study is not a direct support, in that it was looking at how the optineurin protein contributes to ALS. However, the results showed significant increase of the MLKL protein in human patients and that elimination of the RIPK3 protein or inhibition of RIPK1 had modest but nevertheless positive effects on survival of the SOD1 mice (along with positive biological evidence). This suggests that SRG is on the right track with its MLKL study. We believe that acting on MLKL will have a stronger effect without disrupting other cellular functions which depend on RIPK3 and/or RIPK31 (MLKL is involved only in necroptosis).

This study is YOUR study. It would not be position without your support. SciOpen Research Group is the world’s first fully functional “guerilla biotech”. We function only with your support and study pathways other research organizations either miss or ignore. And we can do it for much less because we are purely volunteer and have no overhead. 100% of your donations go directly to research. To support us you can make a tax-deductible donation (USA residents only) by going to our Donations page, purchase some SRG Gear, and/or go shopping on Amazon Smile and name SciOpen Research Group as your charity of choice (we are a registered and approved nonprofit under IRS 501c3). We work on ALS for you, the ALS Community, because we are part of the ALS Community. Help us continue our novel research into eradicating ALS.