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Possible Breakthrough for AIDS Cure
kryonD writes "Researchers believe they have found a new compound that could finally kill the HIV/AIDS virus, not just slow it down as current treatments do. While most of the community is still hesitant to comment on this until it passes peer review, initial results show that their method attacks and kills ALL variations of the virus. A fast track through the FDA could have one of the world's leading problems licked in less than a decade."
Although the scientist doing this work stated, "we would like to formally show this before making any claims that would cause unwanted hype" and the "few AIDS research luminaries" mentioned in the article are not willing to comment this early, it looks like there may already be some interest in Ceragenix Pharmaceuticals' OTC stock which closed at 3.67--up a healthy 122.42% today.
From TFA: "the compound invented by Paul D. Savage of Brigham Young University appears to hunt down and kill HIV.
Although so far limited to early test tube studies, CSA-54, one of a family of compounds called Ceragenins (or CSAs), mimics the disease-fighting characteristics of anti-microbial and anti-viral agents produced naturally by a healthy human immune system."
So basically, unlike other drug treatments which aide the natural immune system by making aids easier to find or retard its progress, this can act as a immune system copy, which is very important for when someone moves from HIV to full blown AIDS.
I don't get it.
The day there is an available cure for AIDS, there will be fucking in the streets.
Bacteria and Yeast are not the same as the acquired immunodeficiency syndrome (AIDS). AIDS and HIV are viruses.
Therefore, speculating that the same thing that stops viruses will also inhibit yeast or bacteria is erroneous. One consists of live cells--the other merely protiens (and is debated whether or not it is 'alive').
A million AIDS patients is about 1/40th of today's problem. Either way, you're painting a pretty damn good picture if your 'prediction' holds true.
My work here is dung.
I'd prefer to just mod this "flamebait" but instead, I'll point out that the "Mormon" church donates millions each year to needy people including 3rd world countries. But hey, you keep smokin' whatever it is that lets you ignore reality in favor of your prejudices.
Oddly enough, despite what may seem like a breakthrough in HIV research, the word "Ceragenin" brings up ZERO hits in Google. If this was really hot or big, you think it should bring up lots of hits.
Who cares about aids? The article states they found a cure for the influenza! No more catching the flu!
(What I say isn't strictly true as some bacteria will mutate at higher rates when subject to certain types of stresse, but that isn't an important part of the mechanism of antibiotic resistance.)
"The White House is not an intelligence-gathering agency," -- Scott McClellan, Whitehouse spokesman.
I have wondered whether HIV/AIDS could be treated by haemodialysis (AKA dialysis); since HIV seems to act on white blood cells (right?), couldn't the blood be cleansed by a miraculous substance such as that in the article? if the miraculous substance itself is toxic, then perhaps that could be filtered from the blood after having been active briefly
unfortunately, cleansing an HIV patient's blood of HIV would probably not be enough to remove HIV from all the tissues in the patient's body, so this process would have to be repeated to keep HIV subdued
GrimRCI'm not exactly a med student either, though I know a little bit about immunodeficiency. While this compound may or may not fight AIDS, it will not work by overcoming the immunodeficiency. It's not possible to replace the functions of a white blood cell with some chemical compound. It's like trying to make honey without bees.
The immune system is one of the most complex systems in the body, and it has one of the most difficult jobs. There is just an incredible array of different cells and substances running around inside a person, and the immune system is required to pick out the few that are hazardous and develop countermeasures to eliminate them. A white blood cell is not merely a little factory that secretes some kind of anti-virus substance -- it's a member of an intricate network of decision-makers.
I have seen the future, and it is inconvenient.
" Further, the compounds appear to have few limits on how they are delivered to patients. Although early indications are for application of CSAs with an ointment or cream, pills or injections may also be developed - if the compound gets to market. "
this actually makes perfect sense considering the economics and regulatory hurdles of FDA clinical trials. *
for a topical NDA (New Drug Application), the costs of a full trial is in the range of 5K-10K per patient. for NDAs that are injected or ingested, the costs are an order of magnitude higher.
furthermore, clinical trials have four steps. pre-clinical, phase 1, phase 2 and phase 3. at each stage, the chances of the trial failing increases quite significantly, resulting in major financial losses. in other words, if the company spends $300M to bring a drug to phase 3 but fails at that stage, the entire cost is completely sunk.
for ingested or injected, the risks of failing at a later stage are much higher than topical drugs. in fact, 1 in 5 drugs that reach phase 3 pass.
considering that the article states that the product is both an anti-viral and anti-fungal agent, there are many applications in the topical space from warts to foot fungus. my guess is that the pharma company will try to quickly bring the drug to market as a topical for these areas due to the above reasons while preparing for clinical trials for HIV/AIDS in parallel.
*the numbers used here are conjected, but scale is about right.
HIV is an enveloped virus, not a naked one. This means that all of the progeny virus particles bud out through the cell membrane, taking a portion of it with them. There isn't the lysis associated with a naked virus, and the cell doesn't simply explode. Infected cells are instead killed off by other, non-infected immune cells which recognize the foreign proteins (from HIV) that are being expressed on the surface of the infected cells.
For a while the body can produce new T-cells as quickly as they can be infected and killed off. Eventually, however, production slows, the T-cell count drops, and full-blown AIDS begins.
Anyway, even if this hypothetical treatment does work, another virus will come out of the woodwork. It's happened pretty much every time we've made any significant progress - why should we expect it to not happen again?
CSA stands for cationic steroid antibiotics and there is a company, Ceragenix, that works on them. Perhaps that's what prompted this made up word?
-Ryan C.
As for the blood-brain barrier: the barrier is made by what are called "glia cells." Or more specifically, astrocytes, a type of glia cells. The lipid membranes of these cells only allow certain molecules that are lipid soluble (non-polar) to enter the brain barrier. That is why when you add only one acetyl group to morphine, it becomes heroin and can act on the brain simply because it is non-polar enough to pass through the barrier. Most anti-viral drugs can indeed get through this barrier. Even if that were not the case though, HIV is a blood pathogen and circulation in and out of the brain would likely be enough to contact all HIV molecules with the anti-viral medication. How else would today's HIV cocktails work? HIV does NOT camp out and slowly kill neurons. At all. It cannot attack neurons. Only t-cells. When enough of your t-cells are attacked and killed, you get AIDS.
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You definitely would NOT mention it to the press if you wanted to get published in a top journal like Nature, Science, or Proceedings of the National Academy of Sciences. They have strict restrictions against talking to the press before the work is accepted and published. If you feel like ignoring these restrictions, then these journals can and will yank your paper. See, for instance http://www.nature.com/nature/authors/policy/embarg o.html.
The article is just an investor communication, published on the Ceragenix website under Investor Relations. Such communications are not the same as scientific journal publications, they just tell the investor where his money is going, usually down the drain. Example :-
PR guy on phone to head scientist : "I've got a hundred shareholders wanting to know why they aren't billionaires yet... do we have any discoveries yet, any liquids that turn green and smoke when you add the blue powder ?".
Head scientist : "Uh, we have something that may go somewhere in a few years, to do with HIV".
PR guy : "Great ! We'll announce that".
The reasoning for the functioning of a CSA as an antiviral seems fairly sound to me- the molecule structurally resembles peptides called defensins, which have potent activity against bacteria and viruses. The method of action, attacking the viral envelope, may make it more difficult for HIV strains to develop resistance. Current HIV drugs target specific molecules involved in the life cycle of HIV- reverse transcriptase, proteases, and the receptors involved in fusion with cells. Minor changes in these molecules could result in resistance to the drugs that target them. An approach based on the general properties of the viral envelope might be more difficult for HIV to sidestep (but by no means impossible).
That being said, I'm curious to know how specificity for HIV will be possible with this line of attack. One of the issues with defensins is that in addition to their direct attack on antigens, they stimulate the immune response in a more general fashion. Which sounds good, except that this stimulation includes inducing mast cells to release histamine, and encouraging the production of cytokines. Too much of those, and you can get anaphylaxis and septic shock, respectively. While this seems like a ludicrous notion for immunosuppressed AIDS patients, it's worth noting that one of the functions of the helper T cells that HIV destroys is to help put the brakes on the immune response once the threat of infection has passed. I'm not saying all CSA drugs would necessarily cause shock in all, or any patients, but I am tossing it out as an example of the sorts of hurdles this and every other promising compound in vitro can face on the way to becoming a drug approved for use in humans- a lot of complicated things are possible in vivo.
"FDA staff reviewers expressed concern about the number of patients who were left out of the study because they died."
It's hard to get that excited about an "in vitro" ("in glass") result. Lots of things work in vitro. There's no indication of whether this works in animals. When they can show it working in mice with human immune systems (there are genetically engineered mice with human immune systems, used for this kind of research), they'll have something. This is a long way from an "AIDS cure".
The reason nobody can find the term "ceragenins" in Google is that compounds of this class are called "cationic steroid antibiotics" in the literature. "Ceragenins" is a PR term.
This company also claims that these compounds can be used to treat cancer, macular degeneration, and multiple-antibiotic resistant infections. They also can be used for skin cream for dry, itchy skin. There's an proposed antiterrorism application, to make smallpox vaccination safer.
However, there are no claims that these compounds improve gas mileage.
Ticker symbol: CGXP.OB. Up 122% today on this press release.
The HIV virus does not "embed" itself into the dna of a victim.
Lesson on the viral life cycle:
HIV --> injects RNA genome + tRNA primer --> reverse transcription to double stranded DNA --> integration ("embedding") into host genome --> transcription of viral genes from integrated HIV DNA to spliced and unspliced mRNA--> translation/export of mRNA and formation of virus particles
It inserts it's rna into t-cells and uses the t-cells to replicate itself. The problem is that this kills the t-cells, thus killing you.
The cause of massive T cell loss in HIV infection has yet to be concretely determined. Direct cell killing due to viral cytopathic effect is not believed to be a major factor. Rather the dysregulation of immune activation, function and apoptosis associated with infection are thought to be the primary causes for T cell loss. Your death is also not a direct effect of T cell loss, but rather the emergence of a combination of opportunistic infections and oncogenic viruses such as Kaposi's Sarcoma Herpesvirus which kills a person.
It does NOT hide away and wait to pop out the second a victim stops taking his or her cocktail.
And actually, the latent reservoir DOES wait to pop out the second a victim stops taking his/her cocktail. It isn't quite as malicious as you imply though...the "popping out" occurs naturally as cells from the resting memory reservoir are activated by antigen stimulus and then reinitiate productive infection. This occurs periodically even when a patient is on medications, but fail to produce virus due to drug blocking virus life cycle. But when a patient has to inevitably stop treatment due to prohibitive cost, toxicity or other side effects, these re-activation events are allowed to proceed and reinitiate full-blown infection.
It cannot attack neurons. Only t-cells.
It has been shown that HIV can enter neurons, but it just fails to produce virus. HIV infects not only T cells, but macrophages as well. Additionally, some groups have reported evolution of viruses which can use their co-receptors as the entry point, opening HIV to a wider range of host cells.
Also, Nature permits formal discussion of these topics at conferences, and the main article mentions this data being discussed at a conference.
Their high-end quote that industry uses is $800 million on average to develop a new drug (hence the name of the book). As I recall, this figure was from a drug-industry sponsored study from Tufts university, and included spiraling costs of clinical trials that somehow seem to cost private industry 10x more to do than government facilities. Maybe the fact that the trials are often expanded for the sole purpose of getting more doctors to use their product has something to do with that.
The low-end quote from Public Citizen/Congress Watch was $170 million per new approved drug. Let's say we settle in the middle at $500 million or so - still far off from $2.2 billion.
As far as pharm companies being business, I totally agree. From a business standpoint, would you rather have a steady income of $6.5 billion per year, or would you rather spend $500 million in R&D and make $10 billion for two years, then see sharply declining sales? Not much of a choice, is it?
Tie that into the fact that $6.5 billion is how much pharm companies make on non-curative HIV medication right now, and $10 billion is a rough estimate for sales (at still ongodly prices of $20k per year per patient) of an AIDS cure. Now you see why pharmaceutical companies have no incentive to actually cure diseases, they'd rather just make medicine that the ailing public has to take for the rest of their lives. After reading that book, this is one area where I think the government actually needs to get more involved.
Or, you could spend inordinate amounts on marketing to press the public into asking doctors for the 'new and improved' medicines that aren't any better than older generic medicines. This is tied to the patent process - once the patent expires, generic manufactures sell the medicine at 1/10 the cost it used to be. The answer? Come out with a new medicine, and push it on the public whether or not it actually provides any benefits over the old version. Then switch your old medicine to be over the counter to stiff the generic manufacturers. Now I know why claritin is OTC, and why I pay 1/10 the cost of it for the generic equivalent at CostCo.
Non-affiliated link to book:
http://www.amazon.com/gp/product/0520239458/103-8
Is that not the very definition of "overpopulated" right there?
They would have the ability to provide food for all their population if it weren't for all the tribal wars over territory. If farmers and their families spend all their time trying to keep out of warzones and having their crops raided by guerilla armies, they don't have the produce or time to set up food-markets. Consequently, the country ends up with famines.
And there is a lot of knowledge required to keep a farm producing food at an optimum level (crop rotation. Look what happened to the farms in Zimbabwe when experienced farmers were displaced by unskilled labourers.
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The one big reason I support AIDS research is precisely because it is a "fashionable" disease. We finally have a virus that the general public, political figures, and media/publicity types will support spending massive amounts of time and money researching a cure for. Every single breakthrough or discovery in researching AIDS helps the research on all of the ther viral diseases out there, that no one has spent much money or time on.
Cancer research has made huge advances in the last 50 years. Bacterial disease prevention and cure is at an amazing level compared to 50 years ago. Genetic disorders, heart disease, allergic reactions, etc. have all had large advances in their areas. The success of these has been due in large part to one or both of two factors. Either some celebrity gets the disease, or supports research into curing it (Jerry Lewis telethon, etc.) or the barriers to research are low, with significant gains acheivable by just finding improved ways of doing what is already being done.
Viral infections, however, are notoriously intractable to anything we try. Until AIDS came along we had very little understanding of how virii operated and what their lifecycle consisted of. Up until AIDS, very few virii were widespread-debilitating-and most importantly-lethal. It is hard to generate the kind of support for research needed to attack the problem with poster diseases like Herpes, Influenza, Chicken Pox, and the Measles. Especially since we have been somewhat successful with the strategy of developing an inoculation then letting all the non-inoculated die off. Worked with Small Pox, almost finished with Polio, if we can get the Africans to stop killing the doctors providing inoculation.
If we can actually figure out how to cure someone from any single virus, the door opens to treatments for the last great frontier of immunological pathology. If it takes jumping on a bandwagon to support battling an entirely preventable disease killing a fashionable (but minor in number to the sufferers of other diseases) portion of society, I'll be right there leading the band and beating the big drum.
"Unheard of means only it's undreamed of yet,
Impossible means not yet done." ~~ Julia Ecklar
Found an article on the compound class in question as showing promises as a broad spectrum antibiotic.
m d=Retrieve&db=PubMed&list_uids=12445638&dopt=Abstr act
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?c
Nothing in it, or found elsewhere, that backs up any antiviral/antiretroviral properties. But, at least another topical antibiotic would be good for medical kits, and for those of us that have minor surgeries done in places like ones feet...