Sunday, August 15, 2010

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).

4 comments:

  1. Thanks for your research, Eric. No salt needed here. Are you considering the phase I trial?

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  2. I am, but am traked so I am excluded..
    :-(

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  3. I recently saw some limited human data indicating that the active ingredient in NP001 can significantly slow progression (decline of function essentially flat during dosages, with a less steep decline following cessation). The data came from a small handful of PALS so is very far from conclusive but does lend toward optimism.

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  4. This substance just initiated Phase 2 trial, which will have longer term dosing over a range of doses. I look forward to the data from this P2.

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