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Old 11-13-2008, 01:29 PM   #1
SpiritWarrior
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Default A cure for AIDS?

http://health.yahoo.com/news/ap/eu_m...treatment.html

BERLIN - An American man who suffered from AIDS appears to have been cured of the disease 20 months after receiving a targeted bone marrow transplant normally used to fight leukemia, his doctors said.

While researchers — and the doctors themselves — caution that the case might be no more than a fluke, others say it may inspire a greater interest in gene therapy to fight the disease that claims 2 million lives each year. The virus has infected 33 million people worldwide.

Dr. Gero Huetter said Wedneday his 42-year-old patient, an American living in Berlin who was not identified, had been infected with the AIDS virus for more than a decade. But 20 months after undergoing a transplant of genetically selected bone marrow, he no longer shows signs of carrying the virus.

"We waited every day for a bad reading," Huetter said.

It has not come. Researchers at Berlin's Charite hospital and medical school say tests on his bone marrow, blood and other organ tissues have all been clean.

However, Dr. Andrew Badley, director of the HIV and immunology research lab at the Mayo Clinic in Rochester, Minn., said those tests have probably not been extensive enough.

"A lot more scrutiny from a lot of different biological samples would be required to say it's not present," Badley said.

This isn't the first time marrow transplants have been attempted for treating AIDS or HIV infection. In 1999, an article in the journal Medical Hypotheses reviewed the results of 32 attempts reported between 1982 and 1996. In two cases, HIV was apparently eradicated, the review reported.

Huetter's patient was under treatment at Charite for both AIDS and leukemia, which developed unrelated to HIV.

As Huetter — who is a hematologist, not an HIV specialist — prepared to treat the patient's leukemia with a bone marrow transplant, he recalled that some people carry a genetic mutation that seems to make them resistant to HIV infection. If the mutation, called Delta 32, is inherited from both parents, it prevents HIV from attaching itself to cells by blocking CCR5, a receptor that acts as a kind of gateway.

"I read it in 1996, coincidentally," Huetter told reporters at the medical school. "I remembered it and thought it might work."

Roughly one in 1,000 Europeans and Americans have inherited the mutation from both parents, and Huetter set out to find one such person among donors that matched the patient's marrow type. Out of a pool of 80 suitable donors, the 61st person tested carried the proper mutation.

Before the transplant, the patient endured powerful drugs and radiation to kill off his own infected bone marrow cells and disable his immune system — a treatment fatal to between 20 and 30 percent of recipients.

He was also taken off the potent drugs used to treat his AIDS. Huetter's team feared that the drugs might interfere with the new marrow cells' survival. They risked lowering his defenses in the hopes that the new, mutated cells would reject the virus on their own.

Anthony Fauci, director of the National Institute of Allergy and Infections Diseases in the U.S., said the procedure was too costly and too dangerous to employ as a firstline cure. But he said it could inspire researchers to pursue gene therapy as a means to block or suppress HIV.

"It helps prove the concept that if somehow you can block the expression of CCR5, maybe by gene therapy, you might be able to inhibit the ability of the virus to replicate," Fauci said.

David Roth, a professor of epidemiology and international public health at the London School of Hygiene and Tropical Medicine, said gene therapy as cheap and effective as current drug treatments is in very early stages of development.

"That's a long way down the line because there may be other negative things that go with that mutation that we don't know about."

Even for the patient in Berlin, the lack of a clear understanding of exactly why his AIDS has disappeared means his future is far from certain.

"The virus is wily," Huetter said. "There could always be a resurgence."



What do people think?
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Old 11-13-2008, 04:00 PM   #2
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Default Re: A cure for AIDS?

I've been studying the mechanism of HIV infection (and bubonic plague infection, for that matter) in class recently. Gene therapy does sound promising, as do several other forms of research on the cure for HIV and AIDS, like inhibitory RNAs (RNAi).
The problem with gene therapy is some of its early experiments killed the patients, making it taboo. That's all I've heard about it, so far.
Thanks for the link, SW!
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Old 11-13-2008, 05:29 PM   #3
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Default Re: A cure for AIDS?

how much is it the virus getting cured or how much is it that the virus is mutating into something else?
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Old 11-13-2008, 06:06 PM   #4
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Default Re: A cure for AIDS?

Well, it seems to me that they're saying they have adjusted the man's genome to incorporate a mutation that stops HIV from entering the cells. This is effective against the most common form of HIV, though there would still be some risk from the other forms.
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Old 11-13-2008, 09:04 PM   #5
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Default Re: A cure for AIDS?

Altering the CCR5 gene does have potential, though I wouldn't hold my breath for a cure just yet.
Note: I could be wrong about any of the below:

What happens normally is that your bone marrow produces cells for your immune system as well as red blood cells for moving oxygen through your blood and platelets to stop your bleeding.
Some of those cells supporting the immune system, mainly the T4-helper cells, are used by the HIV as hosts in which they can multiply. Together with some other tinkering, the disruption of those cells is what eventually causes the immune deficiency - you'll generally have enough HIV in your body to cause problems after 9 years or so.

One of the problems with HIV is that it changes its outward appearance rather a lot. That means it's hard to detect directly, and hard to target specifically with medication.
What doesn't change as much is the core mechanism. By blocking one or more parts of how it finds, enters, multiplies within or leaves a T4 cell you can keep the virus in check.
In the article, they suggest a way to prevent the entry.

Before the virus will try to enter a cell, it has to bump into a couple of receptors it recognizes, like keyholes it has keys to.
For the majority of HIV, one of those co-receptors is CCD5. Another kind uses CXCR4 instead, and there are doubtless other, rarer sorts as well.
CCD5 is also found on other cells playing a part in HIV-1 pathogenesis, like macrophages and dendritic cells.
Of course, the receptor isn't just there to help HIV along but responds to other substances that do belong in your body. Having a lot of those (or artificial variants) means they compete with HIV for available space and while that doesn't block access entirely it can add two years or so to the incubation time.

What's interesting about the CCD5 receptor is that we know there is an uncommon mutation which makes people immune to most HIV infections (called CCR5-Δ32), found mainly in northern Europe. Disabling the receptor that way doesn't seem to have a major impact on one's life, except perhaps that you run a bigger risk of catching something like the West Nile virus instead.

So far so good. But unless you've gotten that mutation from both of your parents, each cell in your body has at least one and probably two CCD5 genes that can tell you how to make proper T-cells, macrophages and so on. If you change some of them, the rest will keep on making suitable HIV hosts.
Luckily, not every cell makes every receptor protein locked inside your genes. For this one we can pretty much narrow it down to the bone marrow.
Which is another stroke of fortune, because bone marrow cells are very easy to find. Unlike most of the rest of your cells they're very active because they have to keep renewing your blood and immune system.

There are two ways to change them. The one used in the article is to destroy the ones you have using cancer medication, after which you are injected with new ones that will hopefully move to the right place and start working before you die of an infection or excessive bleeding. Because the bone marrow cells come from another person, there's always the risk of your body rejecting the cells at which point you're really in trouble.
Bone marrow transplants are definitely not for everyone, but if your aids inhibitors aren't getting the job done and you qualify and you have a suitable donor it might help.

The other is through gene therapy. The idea there is that you send a bit of DNA to your bone marrow cells to change the CCD5 gene so you get a different CCD5 receptor in your T4 cells. Nothing stops working meanwhile, so it would be a much kinder approach.
The difficulty there is that you need to get that information to virtually all of your bone marrow cells, and to their DNA, and to the right place in that DNA, and safely.
One of the most promising approaches for that ironically involves a retrovirus much like HIV itself, though nowhere near as harmful. Optimizing such a process takes a lot of work though so we're not there yet.

While a transplantation or gene therapy doesn't eliminate HIV in itself, it does keep it from multiplying, and one of the single biggest benefits is that it does so without your needing to take medication on a regular basis.
It's easy to see why gene therapy is such a promising field of research, but at the same time the body is such a complex thing there are many challenges to overcome - and public opinion is just one more.
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Old 11-19-2008, 07:42 AM   #6
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Default Re: A cure for AIDS?

Quote:
Originally Posted by SpiritWarrior View Post
Even for the patient in Berlin, the lack of a clear understanding of exactly why his AIDS has disappeared means his future is far from certain.
I guess my "I'm as serious as aids" line now needs a re-think .

Hmm.
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