Wayne, I'm gonna entertain you this last time and then let it go, not because of any other reason than your baiting is so clear and transparent it's almost, no it is a joke.
Through this and the molecule thread you have been "excited", "interested" and "looking forward to" and "hopefull" and yet for a person such as yourself who is so dependant on facts, figures and valid responses and one who constantly warn others not to get ahead of themselves and get caught up in the hype seem to be quite content and positive about something that has provided zero information. How's that work?
Yes Wayne I unlike you are not so accepting of the molecule and yes I am really pissed off by the inconsistant attitude you have and hypocritical moral ground you stand on when it comes to your undying sence of justice for the ALS victims being fooled out of their money and hope, especially when they don't agree with your thoughts or opinions. Oh did I mention that is all you have stated opinion?
Iplex is what it is and again as I have always statetd, if it is of benefit we will never know until it is either trialed, tested in the mouse or we wait for the people taking it to deliver the news, till then all we can do is wait.
Wayne, you do not know wheather Iplex is of value or not, all you are doing is guessing and trying to decifer info that you yourself are saying is questionable, so then why analyse it?
We know were you stand and thats fine.

Richard Dawkins' Science Baloney detector might be useful here:

How reliable is the source of the claim?
Does the source make similar claims, e.g., in other contexts?
Have the claims been verified by somebody else?
Does this fit with the way the world works?
Has anyone tried to disprove the claim?
Where does the preponderance of evidence point?
Is the claimant playing by the rules of science?
Is the claimant providing positive evidence (and not just negating everyone else's)?
Does the new theory account for as many phenomena as the old theory?
Are personal beliefs driving the claim?

How reliable is the source of the claim?
Every study is provided and produced by independent sources from all over the world.
Author has NO interest in any studies at all.

Does the source make similar claims, e.g., in other contexts?
In the context of disease .. no.

Have the claims been verified by somebody else?
All studies have been reproduced in one way or another.

Does this fit with the way the world works?
Yes

Has anyone tried to disprove the claim?
Everyone who says an iron deficiency exists.

Where does the preponderance of evidence point?
Oxidation.

Is the claimant playing by the rules of science?
Every study is provided and produced by independent sources from all over the world.

Is the claimant providing positive evidence (and not just negating everyone else's)?
Yes.

Does the new theory account for as many phenomena as the old theory?
Yes .. whatever the old theory .. was.

Are personal beliefs driving the claim?
Possibly.

---

Herbivore Hypothesis
http://sites.google.com/site/herbivorehypothesis/age-related-iron-accumulation

Minocycline Attenuates Iron Neurotoxicity in Cortical Cell Cultures
Biochemical and Biophysical Research Communications
Jing Chen-Roetlinga, Lifen Chena and Raymond F. Regan, a,
aDepartment of Emergency Medicine Thomas Jefferson University
1020 Sansom Street, Thompson Building Room 239 Philadelphia, PA 19107
Received 4 June 2009. Available online 10 June 2009.


Abstract
Iron neurotoxicity may contribute to the pathogenesis of
intracerebral hemorrhage (ICH).
The tetracycline derivative minocycline is protective in ICH
models, due putatively to inhibition of microglial activation.
Although minocycline also chelates iron, its effect on iron
neurotoxicity has not been reported, and was examined in
this study.
Cortical cultures treated with 10 ìM ferrous sulfate for 24h
sustained loss of most neurons and an increase in
malondialdehyde.
Minocycline prevented this injury, with near-complete
protection at 30 ìM.
Two other inhibitors of microglial activation, doxycycline
and macrophage/microglia inhibitory factor, were ineffective.
Oxidation of isolated culture membranes by iron was also
inhibited by minocycline.
Consistent with prior observations, minocycline chelated iron
in a siderophore colorometric assay; at concentrations less
than 100 ìM, its activity exceeded that of deferoxamine.
These results suggest that attenuation of iron neurotoxicity
may contribute to the beneficial effect of minocycline in
hemorrhagic stroke and other CNS injury models.


Keywords: cell culture; free radical; hemoglobin toxicity;
inflammation; intracerebral hemorrhage; mouse; oxidative
stress; stroke
doi:10.1016/j.bbrc.2009.06.026


Copyright © 2009 Published by Elsevier Inc.

---

Herbivore Hypothesis
http://sites.google.com/site/herbivorehypothesis/age-related-iron-accumulation

This is why I ask.
It seems more time may be lost to trying to figure out how to HIDE how the drug works rather than development.
This is an example of HOW pharmaceutical companies .. **hide** ..
the WHY the drug works.
They are protecting their **investment** .. just like any good
capitalist would and does.


"Someone might steal the drug" ..


"$200/gram .. mimosine" ..


When in FACT .. ? .. all it is is a .. ? .. phytol .. ?


" m-chlorocres-ol "


They tested one of the drugs which is very good in malaria and found
almost ALL of its' efficacy was due TO .. ? .. the preservative they
added.


Out of TWELVE substances IN the drug what did they find .. ?


"Virtually all activity was m-chlorocresol included as a
preservative"


Antileishmanial activity of sodium stibogluconate fractions.
Antimicrob Agents Chemother. 1993 Sep ;37 (9):1842-6 8239593
(P,S,G,E,B)
W L Roberts, P M Rainey
Department of Laboratory Medicine, Yale University, New Haven,
Connecticut 06510.


Sodium stibogluconate, a pentavalent antimony derivative produced by
the reaction of stibonic and gluconic acids, is the drug of choice
for
the treatment of leishmaniasis.
It has been reported to be a complex mixture rather than a single
compound.
We separated sodium stibogluconate into 12 fractions by anion-
exchange
chromatography.
One fraction accounted for virtually all the leishmanicidal activity
of the fractionated material against Leishmania panamensis
promastigotes, with a 50% inhibitory concentration (IC50) of 12
micrograms of Sb per ml; that of unfractionated sodium stibogluconate
was 154 micrograms of Sb per ml.
Further analysis of this active fraction revealed that a major
component was m-chlorocresol, which had been included in the sodium
stibogluconate formulation as a preservative.
The IC50 of pure m-chlorocresol was 1.6 micrograms/ml, a
concentration
equivalent to that present in unfractionated sodium stibogluconate at
a concentration of 160 micrograms of Sb per ml. After ether
extraction
to remove m-chlorocresol, the IC50 of sodium stibogluconate was >
4,000 micrograms of Sb per ml.
In contrast, when L. panamensis amastigotes were grown in
macrophages,
the IC50 of ether-extracted sodium stibogluconate was 10.3 micrograms
of Sb per ml.
The 12 fractions of ether-extracted sodium stibogluconate obtained by
anion-exchange chromatography had IC50s of 10.1 to 15.4 micrograms of
Sb per ml.
We conclude that preservative-free sodium stibogluconate has little
activity against L. panamensis promastigotes but is highly active
against L. panamensis amastigotes in macrophages.
This activity is associated with multiple chemical species.


------------------


"Mimosine currently sells at about $200/g."


http://tinyurl.com/dg5yun


"Chelators maltol and mimosine mobilize iron"


Both maltol and mimosine are found in plants.


"Plant iron chelators mimosine and maltol"


"Maltol"


Comparative study of iron mobilization from haemosiderin, ferritin
and
iron(III) precipitates by chelators.
Kontoghiorghes GJ, Chambers S, Hoffbrand AV.
The heteroaromatic chelators 1,2-dimethyl-3-hydroxypyrid-4-one,
maltol, mimosine and 2,4-dihydroxypyridine-N-oxide, have been shown
to
mobilize iron from human spleen haemosiderin, ferritin and also from
iron(III) precipitates, all containing equal amounts of iron, at
physiological pH.
In the case of almost every chelator, the least-solubilized
polynuclear iron form was ferritin, whereas haemosiderin was more
soluble and the iron(III) precipitate the most soluble of all.
Most of the chelators were more efficient than desferrioxamine at
releasing iron from ferritin, but less efficient in the removal of
iron from the other two polynuclear iron forms.
It is suggested that the chelator differences in iron mobilization
may
be related to variations in the chelator molecular structure, the
protein structure, iron forms and in the mechanism of iron release.


PMID: 3566714


-----------


"Chelators of synthetic or plant origin may carry less risk"


The effect of synthetic iron chelators on bacterial growth in human
serum
J.H. Brock a , Joan Licéaga a G.J. Kontoghiorghes b
a University Department of Bacteriology and Immunology, Western
Infirmary, Glasgow, USA b Department of Haematology, Royal Free
Hospital, London, U.K.
Correspondence to: Dr. J.H. Brock, Dept. of Bacteriology and
Immunology, Western Ifirmary, Glasgow, G11 6NT, Scotland, U.K.
Copyright 1988 Federation of European Microbiological Societies
KEYWORDS
Iron * Chelator * Bacterial growth * Infection
ABSTRACT
Abstract The effect of synthetic iron chelators of the 1-alkyl-3-
hydroxy-2-methylpyrid-4-one class (the L1 series) and 1-
hydroxypyrid-2- one (L4) on bacterial growth in human serum was
compared with those of the plant iron chelators mimosine and maltol
and of the microbial siderophore desferrioxamine.
None of the synthetic chelators enhanced growth of 3 Gram-negative
organisms (Yersinia enterocolitica, Escherichia coli and Pseudomonas
aeruginosa); in some cases they were even inhibitory. L4 strongly
stimulated growth of Staphylococcus epidermidis, but the L1 series
had
only a marginal effect.
Maltol was mildly inhibitory to all 4 bacterial species, while
mimosine enhanced the growth of S. epidermidis and Y. enterocolitica
but had little effect on E. coli or P. aeruginosa. Desferrioxamine
enhanced the growth.
Chelators of synthetic or plant origin may carry less risk of
increasing susceptibility to bacterial infection in patients
undergoing chelation therapy for iron overload than does
desferrioxamine, the drug currently in clinical use.


FEMS Microbiology Letters
Volume 47 Issue 1, Pages 55 - 60
Published Online: 27 Mar 2006


(c) 2008 Federation of European Microbiological Societies. Published
by
Blackwell Publishing Ltd. All rights reserved


---------------------------------------------------------------------------­­­­------


Received 23 September 1987, Accepted 4 November 1987


DIGITAL OBJECT IDENTIFIER (DOI)
10.1111/j.1574-6968.1988.tb02490.x About DOI

---

Herbivore Hypothesis
http://sites.google.com/site/herbivorehypothesis/age-related-iron-accumulation

This is what happens when they start to flatfoot the reason WHY and HOW common everyday drugs work.

"iron chelators"

Antioxidant activity of NSAID hydroxamic acids.
Acta Pharm. 2009 Jun 1;59(2):235-242.
Končič MZ, Rajič Z, Petrič N, Zorc B.
Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.

In the present study, seven hydroxamic acid derivatives of nonsteroidal
anti-inflammatory drugs (NSAIDs) (ibuprofen, fenoprofen, ketoprofen,
indomethacin and diclofenac) were found to possess significant antioxidant,
radical scavenging and metal chelating activities.
The most active antioxidant and radical scavenger was N-methylhydroxamic
acid of diclofenac (ANT = 88.0% and EC50 = 60.1 mug mL-1).
The activity of the standard substance, butylated hydroxyanisole, in the two
assays was ANT = 86.9% and EC50 = 18.8 mug mL-1, respectively.
Ibuproxam was the strongest iron chelator among investigated hydroxamic acids
(EC50 = 255.6 mug mL-1), yet significantly weaker than the standard substance,
EDTA (EC50 = 29.1 mug mL-1).
It seems that different mechanism is involved in metal chelating activity than in
antioxidant and radical scavenging activity.
Antioxidant and radical scavenging activities may be connected with conjugation
of the nitrogen lone electron pair with the carbonyl group.
On the other hand, more hydrophilic substances tend to be better iron chelators.

PMID: 19564147

---

Herbivore Hypothesis
http://sites.google.com/site/herbivorehypothesis/age-related-iron-accumulation

The press release from INSMED implies that the 12 remaining US patients on it will continue to receive it.

http://investor.insmed.com/releasedetail.cfm?ReleaseID=399059

Insmed Provides Update on Supply of IPLEX(TM)
--Company to Provide Remaining Supply of IPLEX(TM) to Ensure Continued Access

RICHMOND, Va., July 27, 2009 /PRNewswire-FirstCall via COMTEX News Network/ -- Insmed Inc. (Nasdaq: INSM), a biopharmaceutical company, today announced that, effective immediately, the Company will cease the supply of IPLEX((TM)) to any new patients. In addition, the Company will not initiate further clinical trials with IPLEX((TM)) at this time. The Company has determined that its limited inventory on hand must be conserved for the treatment of existing patients.

Following the previously announced sale of Insmed's Boulder, Colorado manufacturing facility to Merck & Co., Inc. in March 2009, Insmed no longer has the capability to manufacture IPLEX((TM)), an extremely complicated drug to produce. Moreover, any agreement with a third party to undertake the manufacture of IPLEX((TM)), if it was economically feasible and could be arranged, would not result in production of additional quantities of IPLEX(TM) for at least 12 to 18 months.

There are approximately 70 patients who currently receive IPLEX(TM), 12 in the U.S. and the remainder around the rest of the world. Most of the patients receive IPLEX(TM) pursuant to a court-ordered Extended Access Program (EAP) for Amyotrophic Lateral Sclerosis (ALS) in Italy. The 12 U.S. patients are being treated for ALS under single patient Investigational New Drug applications approved by the U.S. Food and Drug Administration. The Company believes that it has sufficient IPLEX(TM) inventory to supply these patients for no more than 24 months.

The Company intends to analyze the on-going data collected for various indications, including myotonic muscular dystrophy and ALS, and assess the overall IPLEX(TM) development program, including possible IPLEX(TM) manufacturing options with third parties and possible future clinical trials. Initiation of the Phase II clinical trial for ALS patients in the U.S. that had been discussed with FDA earlier this year has been postponed while the Company performs this assessment.

Dr. Melvin Sharoky, Insmed's Chairman, said, "We believe that it is in the best interests of patients who are currently receiving IPLEX(TM) to ensure that our current limited inventory is conserved in order to maintain their drug supply as long as possible, while allowing the Company time to consider its development options."

About Insmed

Insmed Inc. is a biopharmaceutical company with unique protein development experience and a proprietary protein platform aimed at niche markets with unmet medical needs. For more information, please visit http://www.insmed.com.

Forward-Looking Statements

This release contains forward-looking statements which are made pursuant to provisions of Section 21E of the Securities Exchange Act of 1934. Investors are cautioned that such statements in this release, including statements relating to the existing supply of IPLEX(TM) and possible production of additional quantities of IPLEX(TM) by third party manufacturers, constitute forward-looking statements which involve risks and uncertainties that could cause actual results to differ materially from those anticipated by the forward-looking statements. The risks and uncertainties include, without limitation, the available supply of IPLEX(TM) may be used more quickly than expected; we may decide not to pursue a third party manufacturing arrangement for IPLEX(TM); if we decide to pursue such a manufacturing arrangement, we may not be able to find a third party manufacturer willing to produce IPLEX(TM) or be able to negotiate acceptable terms; it may take any third party manufacturer more time than expected to successfully begin producing new supplies of IPLEX(TM) and other risks and challenges detailed in our filings with the U.S. Securities and Exchange Commission, including our Annual Report on Form 10-K for the year ended December 31, 2008. Readers are cautioned not to place undue reliance on any forward-looking statements which speak only as of the date of this release. We undertake no obligation to publicly release the results of any revisions to these forward-looking statements that may be made to reflect events or circumstances that occur after the date of this release or to reflect the occurrence of unanticipated events.

Investor Relations Contact:
Brian Ritchie - FD
212-850-5683
brian.ritchie@fd.com

Media Relations Contact:
Irma Gomez-Dib - FD
212-850-5761
irma.gomez-dib@fd.com

SOURCE Insmed Inc.

http://www.insmed.com
Copyright (C) 2009 PR Newswire. All rights reserved

A.G,

I'm not sure I understand your post. Why do you say that the IPLEX story has ended. From my understanding 12 American patients are still taking it. Although I am not in the "IPLEX" camp as far as believing it works, it hasn't met the end yet that I know. Do you know something more than what was previously posted?

But since we are on the subject one thing has still perplexed me on the whole IPLEX story. Last year, a whole group of PALS and CALS became extremely convinced that IPLEX was a very promising and possibly miraculous (not my word it was what one person described). Okay how did they come to believe that?

Partly it could be traced back to Ben Byer's blog that claimed great things for it. And also after that the Italian program where an Italian patient sued to get it.

Okay but how did all THAT come about? Who first in early 2007 or late 2006 put out the word that IPLEX was a great drug to try? I don't believe for a second that PALS and CALS were reading through technical papers and figured out that this was it and then subsequently plopped down thousands of dollars to try it. Someone led them to believe that it was a great idea in the first place. Who and why?

I don't have the answer but can take some guesses. The one organization that has undoubtedly benefited from the Italian program and PALS here taking it was the small company that makes it. Did they spread the word to neurologists several years ago trying to drum up business?

Thats a good point stopals and when a series of PALS and CALS posted a large set of very motivated opinions of IPLEX in mid 2008 to mid 2009 I had little doubt who was one of the key organizers. Its the 3rd time that I've seen it.

However, I was interested in earlier history. According to multiple web-sites there were 8 PALS in the United States that took IPLEX in early 2007. How did that happen? This drug is very expensive, IGF-1 has been around for a long time and it hasn't really been a spetacular success. So how did the eight PALS in early 2007 get the idea to try IPLEX? To me it seemed to just arise out of nowhere, but of course, that is never the case. Someone had convinced these PALS to try IPLEX in the first place.

Researcher,
I don’t know off the top of my head the source and specifics of the IGF-1 that was used in the three reported trials that took place in the last years – however, as far as I know, that material would not necessarily be substantially different from that described by Tercica. That would be somewhat in contrast to Iplex which would be a very distinct formulation which includes the natural binding partner BP-3 that could potentially influence stability or even activity. Such should not, however, be interpreted that Tercica’s product can’t necessarily have a substantially different activity from whatever had been used in the trials which did not show success but it really would not be expected.

---

John McCarty, PhD
Director of Therapeutic Investigation
ALS Therapy Development Institute