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Medicine Science

Gene Therapy Approach 'Completely' Protects Mice From HIV Infection 190

Pierre Bezukhov writes "Scientists from the California Institute of Technology have come up with a gene therapy approach that has proven effective in protecting mice (with humanized immune systems) against HIV infections. They used a genetically altered virus to infect muscles cells and deliver DNA codes of potent antibodies isolated from the blood of human HIV victims (abstract). The muscle cells then began to manufacture the antibodies in quantities that proved 'completely protective' against HIV infection. By contrast, traditional vaccines have not worked against HIV, as scientists have failed to find a molecule that induces the immune system to produce enough potent antibodies. The difficulties stem from the fact that HIV disguises some of its external structures from the antibodies."
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Gene Therapy Approach 'Completely' Protects Mice From HIV Infection

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  • by scorp1us ( 235526 ) on Friday December 02, 2011 @11:21AM (#38237586) Journal

    How do you conduct a proper trial for HIV? "Here, this is either a drug that will work, won't work, or a placebo which works a surprising amount of time. At best you have a 50/50 shot of getting HIV" Who is going to participate in that trial?

    • by scamper_22 ( 1073470 ) on Friday December 02, 2011 @11:35AM (#38237816)

      You'll never get a proper scientific trial. There are whole areas of medicine we only know because evil regimes like the Nazi Germany conducted experiments without care.

      But you can certainly make a best effort. Inject 1000 random people with either drug, placebo...

      They do whatever they do. They can engage in risky behavior. They can wear condoms. Whatever is. As an experiment, you just assume their behavior is randomly distributed among the 1000 people.

      At the end of the trial, you call them back and see what percentage has AIDS/HIV.
      If all those who received the drug don't have it, and SOME of the ones without it did have HIV/AIDS, then you can say there is a high probability the drug works.

      As I said, statistically you just have to assume that behaviors were distributed evenly among the 1000 person sample.

      If no one comes back with HIV/AIDS... by some miracle that 1000 person trial... everyone suddenly behaves nicely and stops having unprotected sex, no one gets raped... well then the experiment is a failure, but at least 1000 people are not living a good life... so it's a human success.

      • "There are whole areas of medicine we only know because evil regimes like the Nazi Germany conducted experiments without care."

        Tragically that includes the US Government, three years _after_ it had beaten the evil Nazis:

        "President Obama this afternoon spoke with Guatemalan President Alvaro Colom to “express his deep regret” and “extend an apology to all those infected” following the revelation that the U.S. Public Health Service conducted a study from 1946 to 1948 in which near 700 p

    • You are thinking about proving it works. This won't be tested at first. What will be tested at first on humans whether the innoculation itself doesn't kill you. After that it is a matter of simple statistics. As long as the shot doesn't kill you, the rest don't matter. Simple record the patients success at not getting HIV versus non-innoculated patients.

      They are NOT going to shoot up humans with AIDS just for a test. Well. Not officially anyway. This is the medical industry after all. Nazi's would gag.

    • by Jason Levine ( 196982 ) on Friday December 02, 2011 @11:38AM (#38237870) Homepage

      There have already been trials. You give the treatment to one group of at-risk individuals and a placebo to another group. You make sure that they understand that they aren't to rely on this as a cure/certain protection. Then you follow them over the years and see what the infection rate is. If 30% of the control group is infected with HIV at the end and only 5% of the treatment group is infected, you've got a good result. If they are both about the same, your treatment doesn't work.

      • by sorak ( 246725 )

        There have already been trials. You give the treatment to one group of at-risk individuals and a placebo to another group. You make sure that they understand that they aren't to rely on this as a cure/certain protection. Then you follow them over the years and see what the infection rate is. If 30% of the control group is infected with HIV at the end and only 5% of the treatment group is infected, you've got a good result. If they are both about the same, your treatment doesn't work.

        Isn't it also acceptable under some circumstances to give one group the experimental treatment and to give another an existing treatment, and to measure how this experimental treatment works compared to existing alternatives?

        • by Fned ( 43219 )

          It would be, but in this case there IS no existing treatment.

          We have ways to stop people who have HIV from dying, but not a lot of ways to stop them from contracting HIV (aside from the obvious, of course).

    • sed -e 's/HIV/small pox/g'

      This would not be the first time we developed a vaccine against a deadly disease.

      • The smallpox vaccine was tested by intentionally exposing people to smallpox. The medical profession tends to frown on that kind of thing these days.
        • by Belial6 ( 794905 )
          I am betting that letting the drug slip to Africa would lead to human testing that didn't create much more uproar than what is already happening there.
      • by HiThere ( 15173 )

        I don't think this could be called a vaccine. It's intent is not to stimulate the immune system, but rather to supplement it. And the cells generating the supplementation are muscle cells.

    • Re: (Score:2, Interesting)

      by Anonymous Coward

      As I understand it, the way to do a trial with this is to try it in an area where AIDS infection/transmission is common. For instance, test it on a group of prostitutes who don't have AIDS. When you come back a few years later, you check to see if any of your group have acquired the disease, and how their infection rate compares to others in their cohort.

      Also, it's not uncommon to consent to acquiring a disease in the name of research (though they're not typically the lethal variety). I have a c

    • by ceoyoyo ( 59147 )

      You take a bunch of people who belong to a known group with a known average risk. Preferably high risk, because then you need fewer subjects. You give half the the treatment (it's not really a vaccine) and half the placebo. Then you followup and compare the infection rate in the treatment group with that of the placebo group and the known average infection rate.

      But in this case they're using mice.

    • Sometimes, the trials are conducted with people who are currently on HAART (anti-HIV therapy). Their HAART regimens are ended, and the new regimen is given to them. My understanding is that the HIV-infected community is very very understanding--they know that the only chance for a real solution is to volunteer.

      An alternative scenario is to conduct the trial in a high risk population, such as sex workers or people living in sub-Saharan Africa. If you treat enough people, there will be a portion who become
  • I wanna see some peer-review output. I hope I'm wrong, but this sounds too good to be true, like cold fusion or the like.

    Maybe, though, I'm just getting skeptical in my old age...

    But still, I hope I'm wrong.

    • by HBI ( 604924 ) on Friday December 02, 2011 @11:30AM (#38237738) Journal

      The thought that occurred to me was: if your muscle cells have had a coding sequence for an antibody injected into them, aren't they now engaging in effort that has nothing to do with their primary function? Wouldn't that impact things in old age? Wouldn't that increase the likelihood of heart problems, perhaps?

      Then, one might think: why would you want to produce a boatload of HIV antibodies after your years of promiscuous sexual activity are over? Very few of us continue with that behavior ad infinitum.

      • why would you want to produce a boatload of HIV antibodies after your years of promiscuous sexual activity are over?

        Older people have sex too, and they are not strictly monogamous. HIV infections can also be dormant for long periods time, so a person who was promiscuous 10 years ago may find themselves presenting symptoms of HIV infection.

      • by cpricejones ( 950353 ) on Friday December 02, 2011 @12:31PM (#38238798)
        So the goal of the adenovirus is to introduce the broadly neutralizing antibody into T cell lines. These are the immune cells that are going to be ultimately fighting HIV infection, but they lack the right antibodies. In the normal situation, your body raises antibodies, but they cannot bind to the right spot on the virus envelope. Instead, they bind to a spot that the virus naturally varies, and the virus escapes via mutation (i.e., mutated virus replicates, other virus doesn't). In the new situation, the adenovirus provides an antibody that is better, which binds a spot on Env that the virus needs (so virus with mutation at this spot replicate poorly).

        So muscle and heart cells are likely not getting the vector, nor would they be expressing antibodies. Similarly, your body wont continue to raise the antibody if the infection is gone (it will not be ad infinitum).

        This is my understanding ... perhaps others could add key points.
      • Sounds like a lot of speculation based on a minimal amount of information. The less you know, the more you can make up. Rest assured, nobody is going to be injected with this stuff until we know more about it.

        • by HBI ( 604924 )

          Well, isn't that kind of speculation kind of why we bother even discussing such things? Uninformed speculation helps one wrap the mind around new data. Peer-selected random speculation also sharpens up your speculation when you are somehow drawn into a conversation about a topic.

    • Why would it be too good to be true? We now have decades of research on HIV, large amounts of funding for HIV research, and a very real and widely accepted public need. At one time, people would have said that the current treatments for HIV infection sounded too good to be true as well.
  • by mathmathrevolution ( 813581 ) on Friday December 02, 2011 @11:34AM (#38237798)

    The article expresses a concern that once the gene therapy is started it can't be turned off if the person has an allergic reaction to the antibodies. Maybe somebody more informed can explain why:

    1) You couldn't test for an allergic reaction in advance of the gene therapy.

    2) You couldn't just do more gene therapy to turn off your original gene therapy.

    • by Anonymous Coward on Friday December 02, 2011 @12:12PM (#38238420)

      1: Allergic reactions tend to develop over time. You may not be allergic at first, but as a result of constant exposure, you may become so over time. Antibodies are small and soluble enough that this isn't usually a problem, but with a non-self fC region, they can be. We've seen this occasionally with the purification tags used in many common biotherapeutics; if your immune system begins to recognize the tag (his-6 is common) from one therapeutic, any other biologic with the same tag will cause an allergic reaction. Note: this doesn't normally occur with antibody-based therapeutics since they can be efficiently purified without being tagged.
      2: The thing about turning it off is that the off switch has to be hit in the same cells that are producing it; i.e. millions of separate sites. More gene therapy is unlikely to hit *all* of the same cells, and will potentially cause some unintended consequences in non-target cells. The solution is to use a molecular switch. If I were designing it, I'd flank the antibody promoter region and the transcription start site with loxP recognition sequences. Add a cre recombinase gene under the direction of an antibiotic-activated promoter. Basically this would allow you to reverse at least a portion of the gene therapy at will. Take an antibiotic and the affected cells would actually cut out the antibody producing region they introduced. Unfortunately, if you wanted to again have protection, you'd have to undergo the gene therapy again. You could do a similar setup using siRNA under a controlled promoter, but this scheme also has its drawbacks (repression of the transgene therapeutic would only be temporary - which could be better or worse depending on your goals). Anyway, whichever scheme you use will have to be introduced in conjunction with the original treatment; adding it afterwards won't work nearly as well due to the difficulty in getting the treatment to all of the affected cells.

      • Damn, you seem to be a smart mother fucker.

        I'm curious though. In your example, you kill the gene therapy with antibiotics, like a permanent off switch.

        Would it be possible to create gene therapy that is only active in the presence of some external chemical? Forgive my bad example, but could you make it so the gene therapy only activates in the presence of, say, aspirin? That way, after the gene therapy nothing happens, but once you begin an aspirin regimen it would activate, and if there was some allerg

        • Damn, you seem to be a smart mother fucker.

          Just for future thought, "smart" and "educated" are not the same nor always co-located.

      • I too think this should be ranked higher.

    • Someone who is more into biotech could probably do better than I could with this, but here goes...

      1) You could. The problem is that the person wouldn't necessarily have been previously exposed to the antibody that would cause the reaction. Sensitization is a lot more likely once your body's been in contact with the stuff for a while. If someone had some sensitivity to the antibodies[1] before gene therapy even began, it's entirely possible that they've got bigger problems in front of them than getting vacci

  • Promising, but... (Score:4, Interesting)

    by FlavaFlavivirus ( 2021178 ) on Friday December 02, 2011 @11:39AM (#38237876)
    This experiment will probably not produce an actual human drug, as it suffers from the same drawback as most previous gene-therapy studies: the Adenovirus transduction system will kill a significant number of patients. However, the results do seem to indicate that a monoclonal antibody has protective effects. The gene therapy vaccine may not work, but you could inject purified antibody into someone who had a known exposure, or is going to be in a high-risk situation, and prevent infection. Unfortunately, these types of therapies will never be able to cure an established infection, as HIV integrates its genome into host T-cells.
  • by Hentes ( 2461350 ) on Friday December 02, 2011 @11:48AM (#38238042)

    And there are already much better ways to prevent getting infected with HIV.

    • by betterunixthanunix ( 980855 ) on Friday December 02, 2011 @11:58AM (#38238192)
      Unfortunately, the best ways to prevent HIV infection are not within the realm of what can reasonably be expected. People tend to have sex, to not be monogamous, and prefer not to discuss previous sexual partners. Condoms are highly effective but not perfect, and condoms substantially reduce the pleasure men feel while having sex (and I even know some women who do not like the feeling of a condom).

      The reality is that a vaccine or cure for HIV is needed in order for the disease to be eradicated. There is no other way to solve this problem. You will never be able to convince millions (let alone billions) people to be monogamous and to wait until marriage.
      • by Hentes ( 2461350 )

        Now even if we only discuss the practical side of the problem, I would say convincing millions is still more plausible then treating said millions with ridiculosly expensive gene therapy every few years.

        • In some countries, that is more plausible. But in Asia and Africa, where the growth of AIDS is much more prevalent and distrust of drug companies even higher than it is in some Western countries, it's proven to be nearly impossible. There's even a widespread belief in Africa that having sex with a virgin will cure a man of AIDS. This results in a great deal of rape, and when a man is not cured, he often believes that the woman (or very often the young girl) that he raped was not a true virgin and goes lo

      • condoms substantially reduce the pleasure men feel while having sex (and I even know some women who do not like the feeling of a condom).

        I never understood why so many people believe this. Sex is so much more than "penis in vagina"; there's a lot more to kiss, touch, grope, and caress. With a condom it's like 90% as good as without a condom. 90% of awesome is still pretty awesome.

        • I never understood why so many people believe this.

          Perhaps you lack points of comparison? Perhaps you just have different preferences? Perhaps you use some super-awesome brand of condoms (if so, I am going to demand that you tell me which)?

          For me, wearing a condom during sex is like putting seran wrap on my tongue while I am eating.

          • Don't get me wrong, I have a long-term monogamous partner and we never use condoms anymore, so I always get that last 10% of enjoyment. Sex is without a doubt better when there is no condom. But if I wasn't long-term and monogamous, I would rather lose 10% of the pleasure to ensure that I don't get a disease.

            That said, my point was that there is so much focus on "penis in vagina" that it seems like that's all there is to sex, for some people. To me, penis in vagina is about maybe 30% of sex (hence, the c

  • by Christianson ( 1036710 ) on Friday December 02, 2011 @12:00PM (#38238224)
    Maybe this is a silly, minor thing, but it bothers me these sort of blurbs always just talk about faceless "scientists." Does it really take that much work to find out who the principal researchers were? Maybe more people would be inspired to get into science if it actually seemed to come with some measure of face rather than anonymity in a lab coat.
    • The scientists at Caltech don't have faces. They were all destroyed in a series of horrifying Bunsen burner accidents.
  • by Brooklynoid ( 656617 ) on Friday December 02, 2011 @01:31PM (#38239804)
    Now I can have unprotected sex with mice and not worry about getting AIDS
    • by Hentes ( 2461350 )

      These weren't normal mice, but ones with altered "human-like" immune system. Normal mice can't even catch HIV, so don't worry.

All laws are simulations of reality. -- John C. Lilly