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MAGIC Mitochondria (and more)

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 Here (192kbps MP3 for download).

YouTube video version here.

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!

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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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Top 10 Quora Writer

Top 10 Most Viewed Writer On Quora

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Wow! I just stumbled across my full Writer Rankings on Quora (http://www.quora.com). Based on number of views in the last 30 days, I am a “Top 10 Most Viewed Writer” in the following Categories:

  1. Stephen Hawking – #1 with 96,450, #2 has 4,764;
  2. Amyotrophic Lateral Sclerosis – #1 with 86,333, #2 has 194;
  3. Scientists – #2 with 83,523, #1 has 104,262;
  4. Physicists – #2 with 83,290, #1 has 359,824;
  5. Neurological Diseases and Disorders – #3 with 444, #1 has 1,222;
  6. Science – #10 with 83,114, #1 has 234,073.

Also:

  • Neurodegenerative Diseases – #23;
  • Neurology – #31;
  • Charities – #39.

This is very humbling. It’s also quite gratifying to find out that my attempts to share what little knowledge I have gained over the years are deemed useful by others. That’s all I want to do by providing answers on Quora.

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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 – ALS Finding a Cure

Watch These Straight-Talk Videos from ALS Finding a Cure

I’ve invited my friend Dr. Merit Cudkowicz at ALS Finding a Cure to share some important news about what they are doing to help ALS patients and their families learn all they can about the disease. Please read and share.

Every 90 minutes or so, someone new is diagnosed with ALS.

A new patient and his or her loved ones are overwhelmed by a whirlwind of emotions. They are shocked, confused and desperate for information.

So many questions … What exactly is happening to me? What’s next? How long will I live? Will I be able to drive? Or shower? Or go to the bathroom by myself? What happens when I can’t do these things anymore?

At this critical time, patients and caregivers need plain, simple, factual information from experts who care.

That’s why ALS Finding a Cure has created a series of videos to help ALS patients and their loved ones better understand the disease and the resources and support that will be needed as it progresses.

You get facts and insights from the people who know best — individuals living with ALS, their spouses, healthcare providers and professionals. Each of the eight videos brings an honest and straightforward perspective on the impact this disease has on the lives of those touched by it.

We have strived to cover the topics that a patient, caregiver or loved is most concerned or curious about:

  • Overview describes, in layman’s terms, exactly what ALS is and what it will do
  • Resources explains the information, equipment and support networks available to help manage the disease
  • Lean In encourages individuals to realistically prepare for, embrace and take ownership of ALS
  • Relationships provides guidance on maneuvering through the disease and the importance of a journey-long support system
  • And four other videos – Nutrition, Mobility, Hygiene and Breathing & Communication – offer straight talk and on each of those vitally important topics

The video series is an extension of the primary purpose of ALS Finding a Cure, which is to find and fill in the critical gaps in ALS science so that researchers can – one day soon, we hope — develop treatments for and a cure to this disease.

But we are also committed to empowering patients and their loved ones, right now, to be proactive about understanding and managing ALS. These videos are intended to be a resource so that patients and others can make informed decisions throughout their journey.

“Lean in” is more than just the topic of one of the videos; it is the overarching theme for this series. As Eric Valor’s inspiring life makes evident, being proactive is central to understanding, coping with and owning ALS.

We hope you will find these videos to be an effective resource for anyone impacted by ALS.

Dr. Merit Cudkowicz
Chief of the Neurology Department at Mass General
Chief Medical Officer, ALS Finding a Cure

www.alsfindingacure.org

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New Facebook Scam

!!URGENT SCAM WARNING!!

(no, this not about RCH4…)

Do NOT accept any Facebook friend requests from a “Rodney Frisard”. I did, and he immediately started a conversation asking if I had “heard the good news”. I said that I had “been there done that with the whole Jesus thing” (note to others: Please don’t evangelise to me as I really have already been there and done that and am not interested in religion outside of sociopolitical discussions). He responded by telling me some story about how the UN was giving “us” money to combat poverty, and he “noticed my name on the list” when he was supposedly signing his documents for $150,000. Obviously this is a total scam along the lines of a 419 or lottery email scam. When I said I would not be giving my social security or bank information, he deleted the conversation.

Do not give out any personal information to this or any other new “friend”. I don’t know if this is limited to Facebook, but remain vigilant. Beware.

Transcript below:

“Conversation started Saturday
Rodney Frisard: 10/1, 8:57pm
hello,how are you doing?

Eric Valor: 10/1, 8:58pm
all things considered, quite well.

Rodney Frisard: 10/1, 8:59pm
glad to hear from you,hope you heard the good news?

Eric Valor: 10/1, 9:00pm
not to be rude but been there done that with the jesus thing.

Rodney Frisard: 10/1, 9:01pm
About the money grant offer?

Eric Valor: 10/1, 9:04pm
how much to whom from who for what

Rodney Frisard: 10/1, 9:05pm
the united nations are helping us with some grant money this days,they said the money is to help eradicate poverty and maintain a good standard of living, i got $150,000 from them and i also saw your name on their winning list when i was signing my document with them,hope they have contacted you as well?

Rodney Frisard: 10/1, 9:06pm
?

Eric Valor: 10/1, 9:10pm
and a nigerian prince wants to share $40m with me…

Rodney Frisard: 10/1, 9:10pm
who?

Eric Valor: 10/1, 9:12pm
I have been around the internet since before it was the internet. I have seen all these scams before.

Rodney Frisard: 10/1, 9:14pm
scam?

Eric Valor: 10/1, 9:18pm
all you need is my social security and bank account information
not gonna happen.
anything more before I block you, report your profile, and make a very public blog post with international distribution?

**You cannot reply to this conversation.**

[at this point the person deleted the conversation and ran away]

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Neuraltus News!

Phase 2B Enrollment Open Now!

On Thursday, September 22, 2016, Neuraltus Pharmaceuticals announced the commencement of their long-anticipated Phase 2B for their lead candidate NP001. NP001 is a molecule that reverts macrophages (white blood cells) from an activated state where they hunt down and destroy pathogens and injured tissue to a calmer state where they nurture and protect other cells. I have blogged about NP001 extensively in the past. This trial follows up their Phase 2A trial which completed a few years ago. Unfortunately many of the participants in that trial are no longer with us, including my friends Rob Tison and Ben Harris with whom I launched the concurrent Oral Sodium Chlorite Project.

What It Is

This Phase 2B trial is to confirm the results of the post-hoc analysis of the responder class found in the Phase 2A. In that analysis, Neuraltus discovered that patients who were given the highest dose (2mg/kg body weight) and had elevated levels of pro-inflammatory proteins called IL-18 and C-reactive protein responded quite favorably to the drug. If this Phase 2B returns the expected results, NP001 would have a strong case for the same accelerated approval that FDA just granted for the Sarepta DMD drug eteplirsen. We could have the first new treatment since riluzole and the first truly effective one.

Sign Up Now!

I encourage all PALS to use the Clinical Trials tool on my website, provided by our friends at Antidote. It is very important that this trial is fully enrolled as soon as possible so that it is quickly completed and NP001 gets a shot at getting on the market. That is the best chance for it to get to ALL the PALS whose lives could be extended. We did it for the Phase 2A and can do it again for the Phase 2B.

This is a very exciting moment in the history of ALS.