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  • A Potential Cure for AIDS

    Courtesy of THE WALL STREET JOURNAL

    A Bone Marrow Transplant to Treat a Leukemia Patient Also Gives Him Virus-Resistant Cells; Many Thanks, Sample 61

    The startling case of an AIDS patient who underwent a bone marrow transplant to treat leukemia is stirring new hope that gene-therapy strategies on the far edges of AIDS research might someday cure the disease.
    The patient, a 42-year-old American living in Berlin, is still recovering from his leukemia therapy, but he appears to have won his battle with AIDS. Doctors have not been able to detect the virus in his blood for more than 600 days, despite his having ceased all conventional AIDS medication. Normally when a patient stops taking AIDS drugs, the virus stampedes through the body within weeks, or days.
    "I was very surprised," said the doctor, Gero Hütter.

    The breakthrough appears to be that Dr. Hütter, a soft-spoken hematologist who isn't an AIDS specialist, deliberately replaced the patient's bone marrow cells with those from a donor who has a naturally occurring genetic mutation that renders his cells immune to almost all strains of HIV, the virus that causes AIDS.

    The development suggests a potential new therapeutic avenue and comes as the search for a cure has adopted new urgency. Many fear that current AIDS drugs aren't sustainable. Known as antiretrovirals, the medications prevent the virus from replicating but must be taken every day for life and are expensive for poor countries where the disease runs rampant. Last year, AIDS killed two million people; 2.7 million more contracted the virus, so treatment costs will keep ballooning.

    While cautioning that the Berlin case could be a fluke, David Baltimore, who won a Nobel prize for his research on tumor viruses, deemed it "a very good sign" and a virtual "proof of principle" for gene-therapy approaches. Dr. Baltimore and his colleague, University of California at Los Angeles researcher Irvin Chen, have developed a gene therapy strategy against HIV that works in a similar way to the Berlin case. Drs. Baltimore and Chen have formed a private company to develop the therapy.

    Back in 1996, when "cocktails" of antiretroviral drugs were proved effective, some researchers proposed that all cells harboring HIV might eventually die off, leading to eradication of HIV from the body -- in short, a cure. Those hopes foundered on the discovery that HIV, which integrates itself into a patient's own DNA, hides in so-called "sanctuary cells," where it lies dormant yet remains capable of reigniting an infection.

    But that same year, researchers discovered that some gay men astonishingly remained uninfected despite engaging in very risky sex with as many as hundreds of partners. These men had inherited a mutation from both their parents that made them virtually immune to HIV.

    The mutation prevents a molecule called CCR5 from appearing on the surface of cells. CCR5 acts as a kind of door for the virus. Since most HIV strains must bind to CCR5 to enter cells, the mutation bars the virus from entering. A new AIDS drug, Selzentry, made by Pfizer Inc., doesn't attack HIV itself but works by blocking CCR5.

    About 1% of Europeans, and even more in northern Europe, inherit the CCR5 mutation from both parents. People of African, Asian and South American descent almost never carry it.

    Dr. Hütter, 39, remembered this research when his American leukemia patient failed first-line chemotherapy in 2006. He was treating the patient at Berlin's Charité Medical University, the same institution where German physician Robert Koch performed some of his groundbreaking research on infectious diseases in the 19th century. Dr. Hütter scoured research on CCR5 and consulted with his superiors.

    Finally, he recommended standard second-line treatment: a bone marrow transplant -- but from a donor who had inherited the CCR5 mutation from both parents. Bone marrow is where immune-system cells are generated, so transplanting mutant bone-marrow cells would render the patient immune to HIV into perpetuity, at least in theory.

    There were a total of 80 compatible blood donors living in Germany. Luckily, on the 61st sample he tested, Dr. Hütter's colleague Daniel Nowak found one with the mutation from both parents.

    To prepare for the transplant, Dr. Hütter first administered a standard regimen of powerful drugs and radiation to kill the patient's own bone marrow cells and many immune-system cells. This procedure, lethal to many cells that harbor HIV, may have helped the treatment succeed.

    The transplant specialists ordered the patient to stop taking his AIDS drugs when they transfused the donor cells, because they feared the powerful drugs
    might undermine the cells' ability to survive in their new host. They planned to resume the drugs once HIV re-emerged in the blood.
    But it never did. Nearly two years later, standard tests haven't detected virus in his blood, or in the brain and rectal tissues where it often hides.
    The case was presented to scientists earlier this year at the Conference on Retroviruses and Opportunistic Infections. In September, the nonprofit Foundation for AIDS Research, or amFAR, convened a small scientific meeting on the case. Most researchers there believed some HIV still lurks in the patient but that it can't ignite a raging infection, most likely because its target cells are invulnerable mutants. The scientists agreed that the patient is "functionally cured."

    Caveats are legion. If enough time passes, the extraordinarily protean HIV might evolve to overcome the mutant cells' invulnerability. Blocking CCR5 might have side effects: A study suggests that people with the mutation are more likely to die from West Nile virus. Most worrisome: The transplant treatment itself, given only to late-stage cancer patients, kills up to 30% of patients. While scientists are drawing up research protocols to try this approach on other leukemia and lymphoma patients, they know it will never be widely used to treat AIDS because of the mortality risk.

    There is a potentially safer alternative: Re-engineering a patient's own cells through gene therapy. Due to some disastrous failures, gene therapy now "has a bad name," says Dr. Baltimore. In 1999, an 18-year-old patient died in a gene therapy trial. Even one of gene therapy's greatest successes -- curing children of the inherited "bubble boy" disease -- came at the high price of causing some patients to develop leukemia.

    Gene therapy also faces daunting technical challenges. For example, the therapeutic genes are carried to cells by re-engineered viruses, and they must be made perfectly safe. Also, most gene therapy currently works by removing cells, genetically modifying them out of the body, then transfusing them back in -- a complicated procedure that would prove too expensive for the developing world. Dr. Baltimore and others are working on therapeutic viruses they could inject into a patient as easily as a flu vaccine. But, he says, "we're a long way from that."

    Expecting that gene therapy will eventually play a major role in medicine, several research groups are testing different approaches for AIDS. At City of Hope cancer center in Duarte, Calif., John Rossi and colleagues actually use HIV itself, genetically engineered to be harmless, to deliver to patients' white blood cells three genes: one that inactivates CCR5 and two others that disable HIV. He has already completed the procedure on four patients and may perform it on another.

    One big hurdle: doctors can't yet genetically modify all target cells. In theory, HIV would kill off the susceptible ones and, a victim of its own grim success, be left only with the genetically engineered cells that it can't infect. But so far that's just theory. All Dr. Rossi's patients remain on standard AIDS drugs, so it isn't yet known what would happen if they stopped taking them.

    In 1989, Dr. Rossi had a case eerily similar to the one in Berlin. A 41-year-old patient with AIDS and lymphoma underwent radiation and drug therapy to ablate his bone marrow and received new cells from a donor. It is not known if those cells had the protective CCR5 mutation, because its relation to HIV hadn't been discovered yet. But after the transplant, HIV disappeared from the patient's blood. The patient died of his cancer 47 days after the procedure.
    Autopsy tests from eight organs and the tumor revealed no HIV.
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  • #2
    Sounds interesting, but I don't think it will work for EVERYONE, AIDS is a virus, it changes every single time it replicates, which is exactly why there will never be a vaccine for it, there's hundreds of millions of different strains floating around, this will probably be one of the biggest conundrums of all time, how to cure it, in fact the BEST cure is prevention!
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    • #3
      I read that doctor's figured that this would work but before diving in they realised it is just way too inpractical. Bone-Marrow transplant is risky as hell and expensive not to mention 1 patient at a time.

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      • #4
        Then the cure will only be available in China?
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        • #5
          Originally posted by C.Phantasy View Post
          Then the cure will only be available in China?
          What makes you say that?
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          • #6
            Originally posted by skyfalcon888 View Post
            Sounds interesting, but I don't think it will work for EVERYONE, AIDS is a virus, it changes every single time it replicates, which is exactly why there will never be a vaccine for it, there's hundreds of millions of different strains floating around, this will probably be one of the biggest conundrums of all time, how to cure it, in fact the BEST cure is prevention!
            Good point.

            It might sound cruel, but the fastest cure would be to prevent it from spreading. If no one else contracts AIDS after today, then, optimistically, we're probably looking at around 50 years or so before the last infected person dies and the disease dies with them.

            Too bad that won't happen. The disease is spreading rampantly in third world countries where education and protection aren't available. Many, many people who are carrying it don't have any idea that they are HIV+, if they even know what that means.
            Heat89
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            Last edited by Heat89; 12-08-2008, 08:33 PM.
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            • #7
              Originally posted by Heat89 View Post
              Good point.

              It might sound cruel, but the fastest cure would be to prevent it from spreading. If no one else contracts AIDS after today, then, optimistically, we're probably looking at around 50 years or so before the last infected person dies and the disease dies with them.
              Lol, well that sounds logical, just not sure if its probable...AIDS is a retrograde virus, so it in fact spawned from another virus, so whats not to say it'll not happen again? Yet still, intriguing thought, kudos for that! w00t, this bio major is gonna come in handy lol.
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