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aka_gerbil
06-06-2011, 08:31 PM
The next steps to make it more widely available:

For Brown’s cure to be relevant on a wide scale, it would have to be possible to create the delta 32 mutation without a donor and without a transplant—preferably in the form of a single injection. As it happens, progress toward that goal has already begun, in the laboratory of Paula Cannon at the University of Southern California. Instead of a donor, Cannon is using a new form of gene editing known as zinc finger nucleases, developed by the California company Sangamo BioSciences. Zinc finger nucleases are synthetic proteins that act as genetic scissors. They can target and snip a specific part of the genetic blueprint: They can, for instance, cut out the code that produces the CCR5 receptor, yielding a cell with HIV resistance.



I heard someone from Sangamo speak on some of their VEGF work about 5-6 years ago and the lab I was in collaborated with a different lab working with zinc fingers. We still have a ways to go with gene targeting and gene knockouts with non-rodent mammals. (Seriously, rodents are little genetic freaks.) I think the real magic with gene targeting is going to happen when we sucessfully combine zinc fingers with RNAi to supress NHEJ at the same time.

Given my background, my first inclincation is just to genetically engineer things (ie. replace the CCR5 gene with the delta 32 mutation version), but I suppose just snipping the CCR5 code would work too.

Those who do carry the deletion are more susceptible to West Nile. Assuming that they could someday knock out the CCR5 receptor in a reliable way, I'm curious as to what you would see in say, Africa, where you have a lot of both HIV and mosquito-bourne illness.

Gazpacho
06-06-2011, 08:49 PM
And frankly I'm tired of you ruining threads with your personal obsession with me. Get over it and stfu.agalisgv, my opinion of you just went down a big notch. You may not care, but I'm telling you anyway. There are many things I admire about you, and IceAlisa and I have certainly had our disagreements on FSU, sometimes heated. But to tell her to stfu is completely uncalled for, and I'm very surprised to hear that coming from you.

Now, steering back to the topic, the article you link carefully avoids saying it's a cure:


Four years ago, Timothy Brown underwent an innovative procedure. Since then, test after test has found absolutely no trace of the virus in his body. The bigger miracle, though, is how his case has experts again believing they just might find a cure for AIDS.


Methinks some are confusing a cure with something being mass marketed. It was big news when a polio vaccine was discovered, but it took several years before it was made widely available. Didn't negate the importance of the initial vaccine discovery though. I didn't interpret the article as saying it's only a matter of mass availability. The article states,


"For Brown’s cure to be relevant on a wide scale, it would have to be possible to create the delta 32 mutation without a donor and without a transplant—preferably in the form of a single injection. As it happens, progress toward that goal has already begun, in the laboratory of Paula Cannon at the University of Southern California."

I interpreted this as saying that it's possible that this is a real cure and it's only a matter of making it widely available. We all certainly hope so. But the truth is, until researchers find out more, we don't know.

Anita18
06-06-2011, 09:24 PM
Not to seem redundant ;), but ITA!

And ETA that since I currently work in HIV research I was shocked to see that a cure had been found. ;)
That's my reaction whenever someone claims that a cure for cancer already exists and big pharma doesn't want us to know about it and is paying people off to keep quiet. :P I'm always like, "Can we get in on more of this hush money?" :rofl:

aka_gerbil
06-06-2011, 10:04 PM
That's my reaction whenever someone claims that a cure for cancer already exists and big pharma doesn't want us to know about it and is paying people off to keep quiet. :P I'm always like, "Can we get in on more of this hush money?" :rofl:

BWAH! I want some of the hush money too! Where's mine? ;)

VALuvsMKwan
06-06-2011, 10:26 PM
:respec: :respec: :respec:



Jesus H. Christ, coming from you, that's beyond laughable. You post and post and post on subjects acting like you're some self-professed expert on every topic under the sun, and like I've said before, you treat this board, especially PI, like it's your own personal debate pulpit. I don't know if it's your personality type, but you absolutely crave validation and adoration, and since you slimed your way onto this board with a minimal interest in Figure Skating, that's been your M.O.

You behave here as though you are *never* wrong, and will post the most obscure and biased sources from Google-itis to "prove" that you're correct and anyone who disagrees with you is either misinformed, a fool, or an idiot. You need to try looking in a mirror sometime, because that's how you come off a lot of the time.

If IcaAlisa annoys you so damned much, put her on ignore, rather than telling her to STFU.

Oh, snap! I was going to quote Gazpacho's response without having seen this one, but this is EXACTLY how I feel about agalisgv's obsession with one-upping everyone, not just IceAlisa.

Quintuple
06-07-2011, 05:51 AM
So what you are saying that the patient from the Bay Area in question could harbor virus of a different tropism that is currently dormant and is below detectable levels but theoretically (hopefully not!!!) could become active at some point and raise the viral loads again, leading to a new infection?

Yes.

And to expand on the very-likely theory that viruses in a body are not 100% purely of a certain type, sub-type, or tropism, remember, this is a "socially" communicable disease (i.e. through sexual contact, needle or blood sharing, mother-to-infant), so if you do the math, viruses mingle and mingle and mingle in Nth-degree-of-separation contact between those infected. Basically, all the virus in a given body almost *must* be mixed with many of the mutations and divergences any root virus must have created.

I think the more realistic goal for HIV and other terminal illnesses is that we find "functional" cures. i.e. Based on such-and-such combo of medicine, one can expect to survive 150 more years before succumbing to the illness, and since human life expectancy has not gone beyond 120-ish, one can expect not to die of the disease, therefore it's a "functional" cure.

But it also sorta makes sense, based on what else was in the article, that another "functional" cure can be forcing dormancy of virus - i.e. rendering it unable to take over healthy cells and replicate. That'd be another sort of cure.

IceAlisa
06-07-2011, 06:19 AM
Thanks! Sounds like the rush is on to render immunity to the cells one way or another by somehow introducing the delta 32 mutation which by itself theoretically shouldn't be enough to cure HIV anyway. But it's a great start.

However, the question is, how to get rid of the already infected cells? In the case of this patient it was done by chemo since he also happened to have leukemia. But I don't see chemo being a realistic way to go for most other patients who don't have cancer.

Any ideas?

Andora
06-07-2011, 08:53 AM
agalisgv, my opinion of you just went down a big notch. You may not care, but I'm telling you anyway. There are many things I admire about you, and IceAlisa and I have certainly had our disagreements on FSU, sometimes heated. But to tell her to stfu is completely uncalled for, and I'm very surprised to hear that coming from you.



Oh, snap! I was going to quote Gazpacho's response without having seen this one, but this is EXACTLY how I feel about agalisgv's obsession with one-upping everyone, not just IceAlisa.

I think the above is unfair.

The neverending cage match of Agalisgv vs. IceAlisa aside, I don't think that agalisgv necessarily tries to one-up everyone. If she does, she's not even remotely alone in this. :P She doesn't seem to be afraid of telling people when she thinks they're wrong and isn't exactly cushy about it, but that doesn't make her deserving of this.

And I do think they have an affinity for targeting each other, more than others. :shuffle: Not that I want in the crosshairs, mind you...

agalisgv
06-07-2011, 10:08 AM
Icejunkie mentioned this has been known for awhile. But there was a reason why it's been in the news now and why I posted it. So I'll just recap why now, why it's a cure, and why it's significant:

1. Yesterday was the 30th anniversary of AIDS first being published as a new disease in scientific literature. For those interested, here's a chapter that details how AIDS was first identified, and some of the unsung heroes in its detection.

http://m.wired.com/wiredscience/2011/06/aids-how-began-1/

The Berlin case is being reported widely now to commemorate that, and to show how far the medical community has come.

2. The reason why this is being called a cure is because the doctor overseeing the Berlin research finally labeled it as that after several years of testing indicated no resurgence of the virus. Medical bodies have been following suit in calling it a cure as a result.

3. The significance behind the cure, amongst other things, is that the Berlin case was *not* an instance of a functional cure, but rather is a sterilizing cure. While it has been hypothesized that the best researchers could hope for was a functional cure, the Berlin case indicated it may in fact be possible to create a sterilizing cure.

4. The Berlin case provided a moment of retrospective on the past 30 years of AIDS research. What the initial article and mon125 pointed out was research had largely abandoned searching for a cure for some time now. Instead, work was focused on disease management and vaccine discovery. The Berlin case reoriented researchers back onto finding a cure. IOW, a sort of complacency had set in, and this case shook people out of that. Given the early complacency in the early days of AIDS identification, it's rather appropriate that on the 30th anniversary of AIDS research, that that complacency is once again brushed aside.

5. While initially there were questions how broadly the Berlin case could be applied, researchers have already come up with testing protocols to use on more HIV patients, and clinical trials are already underway.

6. While there can be a long pathway from identification of a cure to its mass applicability, researchers are now working towards that where they largely weren't before. Keep in mind the first polio vaccine was discovered a good 15 years before it could be widely used. But eventually it came to pass. Surely there will be bumps along the road and many new discoveries that come out of the Berlin case. But to me none of that negates the significance of this discovery. To me it is no less momentous than the first report identifying AIDS 30 years ago. Others may not see a reason to cheer just yet, but on that we'll have to agree to disagree.

IceAlisa
06-07-2011, 07:56 PM
I think this is unfair: all of us are excited by this development. However, none of the articles I've seen headlined it as a cure for HIV. None of the people who are involved in research who posted here and to whom I have spoken in the past few days consider the cure found. All of the publications cited stated that at this point we don't have a cure that would be applicable to other HIV patients. One patient may have been cured. We don't yet fully understand why and how. This patient also happened to have leukemia and had chemo. I raised the question of how the already infected cells would be removed in patients who don't have cancer. We don't yet have an answer to that.

We hope that the patient will stay HIV free but theoretically it is possible that a virus of a different tropism could re-emerge from the dormant state.
Hopefully, not as mentioned but not enough time has passed to know yet.

So that means we don't yet fully understand how 'the cure' worked. Which of course means we don't yet know exactly how to replicate this result for many reasons I and others have mentioned. This is a case study where the number of subjects is 1.
The race is on to try to excise or otherwise disable the sequence that codes for the receptor but that in itself isn't enough for a cure. We have already discussed why that's the case and the difficulty in understanding why the Berlin patient remained virus free when the donor cells were susceptible to another version of the virus. We don't know why.

Having revitalized the research is an important and welcome development but it does not constitute a cure. At this point we don't have one and don't yet know the exact path to it.

We may have found a principle that will eventually lead to a cure. I reiterate why this is not applicable to the vaccine--the vaccination principle had been around for hundreds of years when the polio vaccine had been discovered. Vaccination had been happening for hundreds of years. Polio vaccine was a matter of development. With vaccines we know that what we do is expose the body to either killed or attenuated pathogen (or parts of it as in the pertussis portion of DTap) and the body develops antibodies to it.

Here we don't yet know exactly how the eventual cure will work and what else needs to be added to the receptor mutation/excision to prevent other types of virus from re-emerging. Perhaps it will be done the same way. But the problem with HIV all along has been it's mutagenic qualities and as Quintiple had explained, the combination of possible different types probably being a high number. That's another difficulty the researchers will face before THE CURE is discovered.

There are a multitude of issues that are not yet resolved, multitude of discoveries yet to be made. I don't think we have the cure yet but we have made an important step towards it in a field that has been stagnating.

Having said that, I do appreciate your attempt to make a point via discussion, agalisgv.

From the AIDS Beacon dated May 12, 2011.

“We currently have no treatments that will eradicate HIV. However, over the next few years I anticipate that there will be an increasing number of clinical trials that will be designed to determine if these [new] strategies will have any impact on residual HIV in patients on combination antiretroviral therapy,” said Dr. Sharon Lewin, director of the Infectious Diseases Unit at Alfred Hospital in Australia and lead author of a recent review on research into potential cures for HIV.
“It is essential that these trials are safe and are designed to answer the question of whether [each] particular approach will ever be feasible,” she added. http://www.aidsbeacon.com/news/2011/05/12/advances-and-barriers-to-a-cure-for-hiv-part-1-types-of-hiv-aids-cures/

Although The Berlin Patient proved that a sterilizing cure is possible, researchers have said his treatment is not feasible for most people with HIV.“A strategy of using bone marrow transplantation with a CCR5 mutant donor is not a realistic cure for HIV given the toxicity and complexity of the treatment,” wrote Dr. Lewin and her coauthor in their review. Additionally, it is still not clear why and how HIV was eliminated in this patient, although scientists continue to study him.
Rather than trying to completely eliminate HIV from the body, some researchers instead have pursued a functional cure. And we are back to what Quintiple has been saying, that the current theoretical emphasis is functional cure. It looks like the use of the word "sterilizing" wrt the body is done in this context, wasn't aware of that.