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going into phase 2 human trials. The article I read talked about the amazing success in their animal trials. i'm so glad i found this and wanted to contribute. full article is here: http://www.nutrapharma.com/investor/pr/10_14_04.htm

hmmmmmmmm.........this is flat-out gene therapy.

Is there enough known yet to do this type of full-bore gene manipulation in MS?

Just wondering.........

Deb

Uh.........I'm not sure if this company is going to be in business long enough for anything to come of this.

Check this out: http://www.sec.gov/Archives/edgar/data/ ... 00404x.htm

And you've got to read this one, also:

http://www.sec.gov/Archives/edgar/data/ ... a10qsb.htm

Here's just a quick excerpt:

"....Nutra Pharma Corp., a development stage company ("Nutra Pharma" or "the Parent") is a holding company that owns intellectual property and operations in the biotechnology industry. The Company incorporated under the laws of the state of California on February 1, 2000 under the original name of Exotic-Bird.com. In October 2001, the Company changed its name to Nutra Pharma Corp. ...."

I'm sorry, folks, but I'd be just a tad "cautious" about this one.

Harry! You out there?? What do you think about this?

Deb

You know, these guys at Nutra Pharma have me intrigued, so I went a little farther on them.

They were into "venoms".........cone snail venom, gila monster venom, and cobra venom. Ok.....there are some useful applications for venom, and research into different venoms (including bee venom, as we all know) is still ongoing, but is in its infancy at this time. Nowhere could I find where it has been seriously researched for actual therapy yet, especially for MS therapy. (And as a side note, it also appears that the poor cone snails are in jeopardy, due to all the ongoing research on them. It takes a lot of snails for a little portion of product. Small numbers mean big profits, also.)

Here's what I did find, though, and it appears it's from a fairly reputable source. I'll highlight the "bottom line", as I call it.

The moral of the story being...........especially combined with the above facts that I located regarding the company itself.........is "buyer beware".

Here's the article. Note the highlighted portion at the end.

Deb
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Nat Rev Drug Discov. 2003 Oct;2(10):790-802. Related Articles, Links

Therapeutic potential of venom peptides.

Lewis RJ, Garcia ML.

Institute for Molecular Bioscience, The University of Queensland, St. Lucia 4072, Australia. r.lewis@imb.uq.edu.au

Nature Reviews Drug Discovery 2, 790 -802 (2003); doi:10.1038/nrd1197

Preface

Venomous animals have evolved a vast array of peptide toxins for prey capture and defence. These peptides are directed against a wide variety of pharmacological targets, making them an invaluable source of ligands for studying the properties of these targets in different experimental paradigms. A number of these peptides have been used in vivo for proof-of-concept studies, with several having undergone preclinical or clinical development for the treatment of pain, diabetes, multiple sclerosis and cardiovascular diseases. Here we survey the pharmacology of venom peptides and assess their therapeutic prospects.

Summary

Toxins have evolved in plants, animals and microbes, often as part of defensive and/or prey-capture strategies. Although non-peptide toxins are typically orally active, peptide toxins are usually found in animal venoms associated with specialized envenomation apparatus that allows their delivery into the soft tissue of animals via subcutaneous, intramuscular or intravenous routes.

Crude venoms contain a diverse array of different peptides, many of which are bioactive. Small peptides present in the venom of cone snails, a family of widely distributed marine molluscs, are highly structured mini-proteins that have evolved in 500 species of fish-, mollusc- and worm-hunting cone snails for rapid prey immobilization and defence. Their small size, relative ease of synthesis, structural stability and target specificity make them important pharmacological probes.

Venom peptides target a wide variety of membrane-bound protein channels and receptors. Of the cone snail venom peptides characterized to date, a surprising number have been found to be highly selective for a diverse range of mammalian ion channels and receptors associated with pain signalling pathways, including the nicotinic acetylcholine receptors (-conotoxins), the noradrenaline transporter (-conopeptides), sodium channels (- and O-conotoxins), calcium channels (-conotoxins), the N-methyl-D-aspartate receptor (conantokins) and the neurotensin receptor (contulakins).

It is well established that Ca2+ influx into nerve terminals through voltage-sensitive calcium channels (VSCCs) is the trigger that initiates neurotransmitter release. -Conotoxins are unique tools with which to identify and determine the physiological role of different neuronal VSCCs and might be potent analgesics for chronic pain.

Like the structurally related VSCCs, voltage-sensitive sodium channels (VSSCs) play a key role in the nervous system. A number of these VSSC subtypes are implicated in clinical states such as pain, stroke and epilepsy. Venoms have evolved to target these channels. Although sodium channel activators are typically toxic, subtypes-elective inhibitors may have considerable therapeutic potential.

Potassium channels are a large and diverse family of proteins implicated in the regulation of many cellular functions. Of the numerous potassium channel-blocking peptides that have been identified, only a small number have shown promising results in animals.

Chloride channels are also among the many membrane proteins overexpressed in different types of cancers. Chlorotoxin isolated from the scorpion Leiurus quinquestriatus binds to specific Ca2+-activated chloride channels and certain tumours and gliomas, and so might have potential in the treatment of cancer.

The first example of a successful venom-based drug is Captopril, which inhibits the angiotensin-converting enzyme, an essential enzyme for the production of angiotensin, a vasoconstrictor associated with hypertension.

As a consequence of their high selectivity, venom peptides have proved particularly useful for in vitro and in vivo proof-of-concept studies. However, for therapeutic applications, a number of issues associated with safety, pharmacokinetics and delivery need to be addressed. It remains to be determined how many of the peptides that are present in venoms can find a clinical utility.

Hi OddDuck,

Elan's Prialt for chronic pain is based off of cone snail venom... it was recently submitted for approval by the FDA.




Small creature, big potential
Cherry Farrow on the snail that may provide a breakthrough in the fight against chronic pain

Thursday February 12, 2004

The Guardian

For thousands of years, medical research has depended on plants, animals and microbes to understand and treat human disease. Now increasing attention is being paid to animals forsources of new medicines. One of the most unlikely and beautifulis a small, deadly mollusc - the cone snail.

There is growing excitement among scientists that this marine snail may provide a breakthrough in the development of a seriesof new painkillers.

Cone snails may contain more medicines than any other animal. A new synthetic drug, Prialt, is now at an advanced stage in clinical trials for the treatment of what is classed as intractablepain - unremitting, untreatable pain. Prialt, derived from the venom or conotoxin of the snail, may be 1,000 times stronger than morphine but without the tolerance or addiction usuallyassociated with opiates.

Cone snails live in shallow tropical waters, on reefs, in mangroveswamps and mud flats. There are thought to be approximately 500 species, although research has focused mainly on three. The snails have a little harpoon or fleshy foot from which theyinject a lethal cocktail of toxins into their prey - other molluscs,worms and fish. They can "shake" the cocktail and create a newmix of changing proportions so their victims cannot develop immunity. Each species has evolved to produce its own set of toxins, about 100, which means there could be as many as 50,000 conotoxins in all.This is unprecedented in the biological world, says AaronBernstein, who is currently conducting research at HarvardMedical School.

"It's the sheer diversity of the chemicals they make. The conesnail is young in evolutionary terms - only 50m years old - yet each has evolved a different number of toxins. Compare this to the 10,000 known alkaloids in plants, which we have been looking at for centuries," he said.

Reseach into cone snails started 20 years ago. Experiments suggest that conotoxins could treat muscle spasticity, following spinal injury and epilepsy, that is resistant to traditional medicines. A broad spectrum anti-epileptic agent is currently inthe first stage of clinical trials.

For years, scientists have searched for a medicine that is veryspecific, effective at low doses and does not cause side effects of addiction or tolerance. Having to keep increasing doses to achieve the same results has always limited the long-term effectiveness of the opiates used for treating severe pain. Conotoxins do not behave like that -they are very potent in small concentrations, as trials carried out on patients with AIDS and cancers have shown.

"Most conotoxins are small peptides, 10 to 40 amino acids in length. They are exquisitely selective about their receptor binding sites," says Bernstein. "This makes them powerful tools for understanding how cells work, as well as a rich source for discovery of new medicines.What is remarkable about them is this ability to be so selective.

"Studies suggest that conotoxins could be used to treat muscle spasticity following spinal injuries and possibly prevent cell death during strokes or head injuries. They may also help in the treatment of small-cell lung cancer. By detecting the antibodies, contoxins can provide an early diagnostic test for some types of cancer. But it is in the treatment of "untreatable" pain that conotoxin research is furthest advanced.

The first large-scale trials show just how effective the new painkiller in its synthetic form may prove to be. Trial results showed no evidence of tolerance or addictive behaviour and in feasibility studies with AIDS and cancer patients with chronic pain there was relief in more than half ofthe patients. All this from a small marine snail that may, in the words of Eric Chivian, founder and director of the Centre for Human Health andGlobal Environment at Harvard Medical School, "contain thelargest and most clinically important pharmacopoeia of any genus"

From: http://www.med.harvard.edu/chge/guardiansnail.pdf

Interesting!!

Yea, I did see where they had found uses for pain, etc., also. And for some cancer uses.

It seems like I had seen something on television some time ago about the cone snail, too.

As far as MS therapy goes, though. Well.............I still think that's jumping a little bit ahead of the game.

I just skimmed past the article that said the cone snail was in jeopardy, due to its decreasing numbers. How will that equate to cost of the drugs derived from the cone snail? I mean until they can repopulate the snail colonies, that is. I wonder how long it takes for a snail to grow to the point of being able to be milked? (I think that's the term they used. Odd, huh?)

You know, now that I think about it, there was something else I ran across........On the NMSS website, I believe, where they had given a grant to someone who is doing research on one of the marine animals for MS. Geez............what was it? Zebra fish or something? No...is that right? Ok....gotta go look it up again. LOL

Deb

Prialt uses a synthetic form of the venom... it would be commercially infeasible if they had to milk cone snails. Not to mention disgusting ;)

hahahahahahahhahahahhahaha............ you DEFINITELY have a point there! Yuck!

Synthetic, huh? hmmmmmmmm.............

(I have to laugh. We can make a discussion out of anything, can't we?)

Deb

AHA! That was correct, zebra fish!! And it was the NMSS who gave the grant. Ok. I'm not crazy after all. (At least not all the time.)

Interesting, huh?

Deb
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William S. Talbot, PhD

Stanford University Medical Center
Palo Alto, CA
Region: Silicon Valley Chapter

Term: 4/1/02-3/31/05

Funding Required: $290,246

“Genetic mechanisms of myelination” Searching for the genes that control the development and repair of the myelin that insulates nerve fibers and which is targeted in MS.

Myelin is a casing of proteins and lipids that insulates nerve fibers, and in the brain and spinal cord, myelin sheaths – and the nerve fibers they encase – are targeted for destruction by the immune system in MS. In order to fully understand how myelin repair can be stimulated, it is necessary to know how its manufacture is controlled. On the most basic level, myelin manufacture is controlled by a host of genes.

William S. Talbot, PhD, and colleagues are taking a pathbreaking approach to defining these myelin genes. The team is taking advantage of the swift reproductive cycle and known genetic makeup of the zebra fish. This animal model has become a major resource in the study of a wide range of human neurobiological problems, since the fish’s myelin and its genetic control closely resemble that of humans. The investigators are creating gene mutations that cause significant myelin abnormalities, then tracing the genes and determining their functions in relation to myelin manufacture.

Ultimately, this unique project will lead to better understanding of the processes through which myelin is manufactured, and may offer new targets for drug therapies that can optimize myelin repair in persons with MS.

You know what I just thought of? Perhaps I should clarify this, also. I think this comes from my "precise" use of words.

When I use the word "therapy", it means something different than "treatment". When I say "treatment", I mean it more in the terms of relief of symptoms, i.e. symptomatic treatment. Use of the word "therapy" denotes actual relief from the disease process itself. "Therapy" means a bigger picture, as in positively affecting and/or correcting the causal relationship of a disease or syndrome.

So, as in the above discussion, venom shows many uses for treatments in disease (i.e. pain relief, etc.), but as far as "therapy" for MS...........that to me is going a little too far just yet, as that appears to me to still be in its infancy. So MS therapy seems to be putting the cart before the horse in this particular case. (That's just giving an example of what I mean.)

That's what I get for talking with certain medical professionals. HAH! Combine that with legal jargon, and you've just created a wordsmith monster.

Don't ask me why I thought I should clear that up.

Deb