Just an update to all. I am continuing my sodium chlorite but doing it via IV still. This doesn't mean I don't think the oral route works just as well, the goal is to show that injecting off the shelf sodium chlorite is not harmful (if you follow sensible sterile technique). I had a port placed because I was only able to get the IV started about 50% of the time. With the port I will be able to schedule my infusions better.

I was about to give up on sodium chlorite but I noticed an improvement after my last infusion. It seemed to last about one week so I am going to try one infusion every week and see how that goes.

Thanks!

Ben

---

If it is done in secret, it is done in vain.

Oops. Brain fart. I meant L-Arginine as a precursor to NO. That's the thing ichisan. Your goal appears to be the increase in vasodilation, yet a substance you are using could very possibly be aggravating an established pathophysiological mechanism in ALS. But then again, what is the adaptive response of the body to oxidation? and what is the insult? Like Nemesis says, is it cause, effect, or result?

Please don't misread me. I support anyone with anything they choose to do in order to help themselves with this crappy disease. It's just a query I have each time you write about mega-doses of L-Arg. (At least you are also giving L-lysine).

Would this be a reason for the OSC to work less well in bulbar onset SALS? Over-oxidized Form of Superoxide Dismutase in Sporadic Bulbar ALS Shares Toxic Mechanism with Mutant SOD1
March 20, 2012
Piera
Piera Pasinelli, Ph.D.

A recent study published in the Proceedings of the National Academy of Sciences (PNAS) explored the role of Cu/Zn Superoxide Dismutase 1 (SOD1) found in sporadic ALS with bulbar onset. The team led by ALS Association-funded investigator Piera Pasinelli, Ph.D., Thomas Jefferson University, Pennsylvania, asked whether post-translational modifications to SOD1 could lead to disease in sporadic ALS cases.

“This is an extremely important question to answer as it has implications for treatment approaches currently aimed only at 2 % of ALS cases linked to SOD1 mutations, and may also have benefit for other cases of ALS,” said ALS Association Chief Scientist Lucie Bruijn, Ph.D.

Analysis of SOD1 isolated from patient-derived lymphoblasts – immature cells which typically change to form mature lymphocytes (white blood cells) – from a subset of bulbar onset patients by a technique called “immunoprecipitation” identified iper-oxidized SOD1, which is above baseline oxidation levels. Interestingly this was seen in seven cases of bulbar ALS not seen in four cases of familial ALS or 13 cases of lower and upper limb onset. Ten healthy controls were also included in the analysis. Similar to mutant SOD1-like properties, iper-oxidized SOD1 isolated from sporadic bulbar onset cases formed a toxic complex with mitochondrial Bcl 2, when further stressed.

There was no correlation between the appearance of the iper-oxidized SOD1 and patient’s sex, age, or duration or progression of disease. However, it did correlate with bulbar onset, highlighting that the underlying mechanism in various subsets of ALS may differ and, with further validation of levels of iper-oxidation, may provide a biomarker to define various subsets of ALS as well as have therapeutic implications.

“This is the first time that it is shown in patient derived cells that SOD1 is a target and a marker of disease in sporadic ALS,” said Dr. Pasinelli. “Rather than a misfolded and unstable SOD1, it is an over-oxidized SOD1 that pre-disposes the cells to an age-or-environmental stress that ultimately trigger disease.”

This new study was supported by The ALS Association with funds from its Greater Philadelphia Chapter. Visit http://www.pnas.org/content/early/2012/03/09/1115402109.long to read the full report in PNAS.

Previous studies suggest that misfolded SOD1 may not only be a cause of familial cases of ALS linked to SOD1 mutations but also a cause of sporadic ALS cases. In an August 2011 report, investigators led by Brian K. Kaspar, Ph.D., Ohio State University School of Medicine, concluded that astrocytes isolated from post-mortem cases of ALS resulted in motor neuron damage; furthermore, the damage could be reversed by lowering SOD1 in these astrocytes. To read about this study, visit http://www.alsa.org/news/archive/astrocytes-toxic-to-neurons.html.

Dr. Pasinelli continued, “We, of course, need to confirm our data using a large cohort of patients, but we are glad to see that the presence of an over-oxidized SOD1 seems to correlate with bulbar onset, leading to the possibility to sub-classify sporadic ALS based on specific biomarkers.”

Thanks, Nemesis. I agree it would be good to try to differentiate the participants in the anecdotal studies. It also appears that the participants in most of the large controlled studies are not very clearly differentiated. I am impressed, however, with the recent apparent spike in basic research, especially now that stem cell technology is being used. The mice don't appear to be that useful. Best to all. Mark

Hi Olly, One wonders what, if any, followup studies are in progress or have been done on the activated protein C. I will try to find something. Thanks for your followup. Mark

Thanks Rob for the leads..


Looking at APC............Protein C
From Wikipedia, the free encyclopedia

Cytoprotective effects

When APC is bound to EPCR, it performs a number of important cytoprotective (i.e. cell-protecting) functions, most of which are known to require EPCR and PAR-1. These include regulating gene expression, anti-inflammatory effects, antiapoptotic effects and protecting endothelial barrier function.[6]:3162

Treatment of cells with APC demonstrates that its gene expression modulation effectively controls major pathways for inflammatory and apoptotic behaviour.

There are about 20 genes that are up-regulated by protein C, and 20 genes that are down-regulated: the former are generally anti-inflammatory and antiapoptotic pathways, while the latter tend to be proinflammatory and proapoptotic.

APC's mechanisms for altering gene expression profiles are not well-understood, but it is believed that they at least partly involve an inhibitory effect on transcription factor activity.[6]:3162,4 Important proteins that APC up-regulates include Bcl-2, eNOS and IAP. APC effects significant down-regulation of p53 and Bax.[12]:2388

APC has anti-inflammatory effects on endothelial cells and leukocytes. APC affects endothelial cells by inhibiting inflammatory mediator release and down-regulating vascular adhesion molecules. This reduces leukocyte adhesion and infiltration into tissues, while also limiting damage to underlying tissue.

APC supports endothelial barrier function and reduces chemotaxis. APC inhibits the release of inflammatory-response mediators in leukocytes as well as endothelial cells, by reducing cytokine response, and maybe diminishing systemic inflammatory response, such as is seen in sepsis. Studies on both rats and humans have demonstrated that APC reduces endotoxin-induced pulmonary injury and inflammation.[6]:3164

Scientists recognise activated protein C's antiapoptotic effects, but are unclear as to the exact mechanisms by which apoptosis is inhibited.

It is known that APC is neuroprotective.
APC's antiapoptotic effects are part of the reason that APC is effective in treating sepsis, as reduced levels of apoptosis are correlated with higher survival rates in septic patients.[6]:3165 Antiapoptosis is achieved with diminished activation of caspase 3 and caspase 8, improved Bax/Bcl-2 ratio and down-regulation of p53.[12]:2388

Activated protein C also provides much protection of endothelial barrier function. Endothelial barrier breakdown, and the corresponding increase in endothelial permeability, are associated with swelling, hypotension and inflammation, all problems of sepsis. APC protects endothelial barrier function by inducing PAR-1 dependent sphingosine kinase-1 activation and up-regulating sphingosine-1-phosphate with sphingosine kinase.[6]:3165

---

Into the heart, an air that kills, from yon far country blows.
What are those blue remembered hills, what sphires what farms are those.
That is the land of lost content,I see it shining plain,
The happy highways where I went and cannot come again

Down regulating of SOD has to be selective....

Schwann cells expressing dismutase active mutant SOD1 unexpectedly slow disease progression in ALS mice

Neurodegeneration in an inherited form of ALS is non-cell-autonomous, with ALS-causing mutant SOD1 damage developed within multiple cell types. Selective inactivation within motor neurons of an ubiquitously expressed mutant SOD1 gene has demonstrated that mutant damage within motor neurons is a determinant of disease initiation, whereas mutant synthesis within neighboring astrocytes or microglia accelerates disease progression. We now report the surprising finding that diminished synthesis (by 70%) within Schwann cells of a fully dismutase active ALS-linked mutant (SOD1(G37R)) significantly accelerates disease progression, accompanied by reduction of insulin-like growth factor 1 (IGF-1) in nerves. Coupled with shorter disease duration in mouse models caused by dismutase inactive versus dismutase active SOD1 mutants, our findings implicate an oxidative cascade during disease progression that is triggered within axon ensheathing Schwann cells and that can be ameliorated by elevated dismutase activity.

Thus, therapeutic down-regulation of dismutase active mutant SOD1 in familial forms of ALS should be targeted away from Schwann cells.

http://www.mendeley.com/research/schwann-cells-expressing-dismutase-active-mutant-sod1-unexpectedly-slow-disease-progression-in-als-mice/

---

Into the heart, an air that kills, from yon far country blows.
What are those blue remembered hills, what sphires what farms are those.
That is the land of lost content,I see it shining plain,
The happy highways where I went and cannot come again

That is a very commonly reported side effect. I am not a neurologist so take what I say with a grain of salt. That a person is having fasciculations at all is a sign the there has been motor neuron death. However, a sudden increase in fasciculations might actually mean that some of your neurons which had been suppressed are now reactivated.

I don't think this theory has any scientific research to back it up that I know of, It is something we came up with to explain why some of us felt and increase in fasciculations and concurrent increase in muscle strength while on the NP001 trial.

Thanks,

Ben

---

If it is done in secret, it is done in vain.

Fasiculations is (in my case) because of a lack of circulation and oxygen. I've had them dissapear and I know why because I've had oxygen and circulation deprevation return to normal and with that all the fasics completely dissapeared.

---

http://borreliawenttofar.wordpress.com

This discussion blog may not be pertinent to this question, but anyway I am going to do it and on few others where there is lot of activity. Those who can share some light perhaps can make it as PM if necessary.
My daughter, because of frustrations on her part, decided to go global through Facebook and forcing us for a quick decision. We still cling on to to some hope what if it is not ALS and something else (and fear that we may end up regretting to agree with her decision in such a case) since we see many things unique in her. Let me post two specific ones and get the take from PALS and caregivers.
1. Look at the statement from Sandra Lesher Stuban, RN who wrote (in recent ALS newsletter etc):
Advice from the trenches: Top 10 list of equipment:
7. Heating blanket / Space Heater:
I am always cold because I no longer have the muscle mass to generate and maintain heat. My solution is to use an electric (heating) blanket on my bed at night and a space heater in my bathroom where I change cloths and shower. When I start my days warm, I feel letter all day long.
In our case it is exactly opposite: We have been keeping the temperature at around 61 degrees, because that is what she prefers and starts sweating if it is any high. She sits in front of the computer most of the time when awake and wears simple dresses, T-shirts etc. and no sweaters or anything.
2. I also thought that ALS folks do not feel pain that much having lost the muscles. Again she is different.
3. Sensory system and brain power: Her sensory system and intelligence have become great. She gets hurt with small things such as the tags on undergarments or wrinkles on T-shirts and she is not lying. She can spot an ant or a small bug on the wall 10 feet away and ask this guy who wears a glass with a power of -12 to remove it! Or she will point to one hair on a black dress or on her bare hand and insist on us removing it. She moved from a struggling medical school student, understandable since every body going there is intelligent and highly competitive to one with great scores in national medical board exams with minimal preparation and finished the degree in minimal time with all travels to Mayo, JHU etc. as the disease progressed. So, it is confusing.
I am going to raise it with our local Neurologist, but of course, he will have his standard answer (like I like only FDA authorized drugs!) Each patient is unique.
Thanks, OG.