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New prophylactic treatment produces 80% reduction in mortality in mouse model trial

V

Vibrant62

Senior Moderator
Abstract

http://www.intmedpress.com/Journal ...74500014F25450E054401252149005948470455096B01


Effect of oral gavage treatment with ZnAL42 and other metallo-ion formulations on influenza A H5N1 and H1N1 virus infections in mice
Dale L Barnard, Min-Hui Wong, Kevin Bailey, Craig W Day, Robert W Sidwell, Stephen S Hickok and Tony J Hall
Antiviral Chemistry & Chemotherapy 2007; 18: 125-132

Avian influenza H5N1 infections can cause severe, lethal human infections. Whether influenza A virus treatments effectively ameliorate avian influenza H5N1 human infections is uncertain. The research objective was to evaluate the efficacy of novel zinc and other metallo-ion formulations in two influenza A mouse models. Mice infected with influenza A/Duck/MN/1525/81 (H5N1) virus were treated orally 48 h before virus exposure and then twice daily for 13 days with ZnAL42. The optimal dosing regimen for ZnAL42 was achieved at 17.28 mg/kg 48 h prior to virus exposure, twice daily for 7 days. The survival rate was 80% compared with 10% in the untreated control group and a 100% survival rate with ribavirin (75 mg/kg/day, twice a day for 5 days, beginning 4 h before virus exposure). ZnAL42 treatment significantly lessened the decline in arterial oxygen saturation (SaO2; P<0.001). This regimen was also well tolerated by the mice. Manganese and selenium formulations were not inhibitory to virus replication when given therapeutically. Mice were also infected with influenza A/NWS/33 (H1N1) virus and were treated 48 h before virus exposure with three dosages of ZnAL42 (8.64, 1.46 or 0.24 mg/kg/day). Treatment was by oral gavage twice daily for 13 days. The highest dose of ZnAL42 was significantly inhibitory to the virus infection as seen by prevention of deaths and lessening of decline in SaO2. The data suggest that the prophylactic use of ZnAL42 is effective against avian influenza H5N1 or H1N1 virus infection in mice and should be further explored as an option for treating human influenza virus infections.
Keywords: animal model, avian influenza, H5N1, influenza A, zinc
 
Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

any idea, how the zinc works ?
Any correlation with zinc in nutrition with
occurrance and severety of flu-epidemics in history ?
 
Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

Never heard of : ZnAL42?

Anyone has information?
 
Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

is it Zn + Al ( aluminium) ?
in oligotherapy, you may have mixed ions, with a synergyc action : Zn Ni Co, MnCo, etc...
 
Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

From Journal of the American Pharmacists Association

Efficacy of Zinc Against Common Cold Viruses: An Overview

Posted 11/23/2004

Darrell Hulisz

Abstract and Introduction

Abstract

Objective: To review the laboratory and clinical evidence of the medicinal value of zinc for the treatment of the common cold.

Data Sources: Published articles identified through Medline (1980-2003) using the search terms zinc, rhinovirus, and other pertinent subject headings. Additional sources were identified from the bibliographies of the retrieved articles.

Study Selection: By the author.

Data Extraction: By the author.

Data Synthesis: Human rhinoviruses, by attaching to the nasal epithelium via the intracellular adhesion molecule-1 (ICAM-1) receptor, cause most colds. Ionic zinc, based on its electrical charge, also has an affinity for ICAM-1 receptor sites and may exert an antiviral effect by attaching to the ICAM-1 receptors in the rhinovirus structure and nasal epithelial cells.

Clinical tests of zinc for treatment of common colds have been inconsistent, primarily because of study design, blinding, and lozenge contents.

Early formulations of lozenges also were unpalatable. In three trials with similar study designs, methodologies, and efficacy assessments, zinc effectively and significantly shortened the duration of the common cold when it was administered within 24 hours of the onset of symptoms.

Recent reports of trials with zinc gluconate administered as a nasal gel have supported these findings; in addition, they have shown that treatment with zinc nasal gel is effective in reducing the duration and severity of common cold symptoms in patients with established illness.

Conclusion: Clinical trial data support the value of zinc in reducing the duration and severity of symptoms of the common cold when administered within 24 hours of the onset of common cold symptoms.

Additional clinical and laboratory evaluations are warranted to further define the role of ionic zinc for the prevention and treatment of the common cold and to elucidate the biochemical mechanisms through which zinc exerts its symptom-relieving effects.

http://www.medscape.com/viewarticle/491043
 
Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

I remember they recommended "zincal" or such for seasonal flu or for colds
on another board

zinc +influenza at pubmed gives:

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Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

thanks Dutchy, you were faster

znal42 = ZnAl(2)O(4) ?
 
Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

does anyone know if there are any commercial preps that contain this ingredient?
 
Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

I can answer most questions. I have been involved (peripherally) inthis project in London, so know a great deal about it. For interest, Remedy Research has also produced some astounding work on MRSA and C Diff control - will post the abstract and link to full paper as soon as I can get to it, which has just been published. This MRSA study was done in association with University College London. The H5N1 study was done in the US on NIH grant funds. Further work is ongoing.

ZnAL42 is the study code for the product, which will be marketed under a trade name, yet to be determined - but probably in the US before the EU because of Regulatory issues. Working on the EU issues.

Simply put, the benefits are unique to this formulation. I dont have time right now, but will post something of a workshop and references that will be useful. If you can get access to the full paper it is worth it - there were numerous highly charged ionic zinc preparations tested pre trial, only two showed any promise and went forward for evaluation. In the full mouse model, only one showed any significant reduction in mortality. Furthermore this benefit was lost when combinations were tried with selenium and manganese metallo ion products.

We dont fully understand the precise mechanism. We can't explain why one ionic zinc formulation works and the others dont - this is (IMHO) probably entering the realms of biophysics.

Furthermore, efficacy works on highest study dose bd, but when split across tds or qds dosages, the benefit falls away - so dosage and frequency of dosage are very, very important: note - this trend works in the opposite way to a normal pharmaceutical response curve.

The paper gives some proposed mechanisms - but its going to be a bit more complex than this. Sorry to have more questions that answers in many senses, but the important thing is, its promising. There are enormous amounts of human data on zinc used at this sort of dosage for treatment of sickle cell anaemia and smell and taste disorders - and toxicity data looks good form these in-vivo trials appears good.

A human trial is needed - this is being worked on, and we hope that this will get taken up by the CDC. However, if these results do fully translate, in the early stage of a pandemic it is my belief that this product could help to significantly reduce morbidity and mortality, especially whilst vaccines and anti-virals are in short supply. It can also be easily and rapidly manufactured. It does not replace the need for either intervention (or others in development) as 20% of the study animals still died - rather it is a potentially valuable addition to the armoury. We think it helps to prevent the initation of a cytokine storm, and we are working developing proof / further evidence of this at present.

I propose to simply post papers and links that might be useful and let you all discuss amongst yourselves, and reach your own conclusions. Please pm me with specific questions.
 
Last edited:
Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

is it also useful to reduce the spread or only for treatment ?
ribavirin is still better for mice (100%)
 
Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

Prophylaxis only - if taken 48 hours before innoculation, protection is conferred. If taken after infection, benefit it not the same, and is marginal. What this would imply is that people would need to start taking this at the outbreak of a pandemic wave and continue throughout it, as you would not know when you would be exposed to the virus.

It would need to be taken twice daily, from the time that a pandemic wave was declared.
 
Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

Additional note: Ribavarin was used as a postive control in one arm of the study and tamiflu in another.
 
Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

yes, but when treated people or people on prophylaxis
also shed fewer virus
that could stop the whole wave.
So I'm not only interested in treatment...
Is this effect expected to be similar to Tamiflu-blanket-strategies ?
 
Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

It would be nice if some of the epidemiologists would run such scenario's to see what effect it would have. It has been dififcult to reach the individuals concerned but we are trying.

Bottome line - we dont know. A simulation needs to be run. Someone with the skills needs to do it. We hope that the publication may stimulate some interest.
 
Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

how long would it take to produce -say- 1billion doses, if panflu starts tomorrow ?
what would it cost ?
 
Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

First question: if the production plants are set up, not long. This takes money to get initiated, but once done, the rate limiting steps are availability of bottles and factors like that.

Re costs: I don't know - outside my remit. I dont think any of this is absolutely decided yet, and there are many, many issues to be resolved. But if there is interest, price will fall as economies of scale from mass production are reached.

It is to be hoped that the R&D outfit behind this gets the right interest to facilitate mass production quickly. If not, expect a higher price in the early stages, i.e in a non-pandemic world . But this is just my guess - as, as I said above, this is outside my remit. I just dont know.
 
Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

Re: New prophylactic treatment produces 80% reduction in mortality in mouse model tri

For MRSA eradication data from same research company see
http://www.flutrackers.com/forum/showthread.php?t=29162

This is relevant insofar as understanding that this is a novel technology - it is down to the nature, and charge of the formulation - and that this goes across applications.
 
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