Doctors Will Test Gene Editing On HIV Patients 263
Soychemist writes "Some people have a mutation that makes them highly resistant to HIV, and scientists think that they can give that immunity to anyone with a new type of gene therapy. The first human trials will start at the University of Pennsylvania this week. Researchers will draw blood from people with drug-resistant HIV, clip the CCR5 gene out of their T-cells with a nuclease enzyme, grow the modified cells in a dish, and then return 10 billion of them to the patient's bloodstream. Those cells will be immune to the virus, and they will keep the patient's T-cell count up even if the rest are destroyed. 'We will see if it is safe and if those cells inhibit HIV replication in vivo,' said the lead researcher. 'We know they do in the test tube.'"
Re:Sounds expensive... (Score:5, Informative)
There are people who were born HIV+ because their mother was a carrier, there are people who have been raped and now carry the virus, there are people in the medical field that contract it because some drug addict freaks out while they tend to them. Hell, even though we test blood now many people contracted it through blood transfusions before they tested it.
Oh and by the way. Condoms don't give 100% protection against HIV its about 80-85%.
HIV is a bastard of a virus. Our immune systems can usually handle most viruses without intervention. You cant win on your own against HIV. It will destroy the immune system eventually.
If this treatment is successful at this level. At least we can give life to those who didn't have the choice.
Re:might as well guinea pig at that point (Score:5, Informative)
Mod parent down - didn't RTFA (Score:4, Informative)
The test subjects have drug resistant HIV.
Potential Failure RIsks: (Score:5, Informative)
There are 3 big risks / problems I see with this approach:
#1: The modified T-Cells attack the host after they are reintroduced. Think of it like auto-immune disease or transplanted-organ rejection. This could cause effects ranging from a mild food allergy to death. Anyone know how much damage 10 billion rogue T-cells could do? I sure don't; however, I do know that they aren't a straight 1 T-Cell used up for each 1 antigen.
#2: Unmodified T-cells attack the modified T-Cells because the surface of the modified T-Cells (i.e. the CCR5 protein) could possibly trigger an immune response. This would render the modified T-Cells kind of pointless. Seems like this would have better chance of working on patients with full blown AIDS rather than merely HIV+.
3: Modified T-Cells survive and are unaffected by HIV; however, these surviving modified T-Cells are just clones of the one original T-Cell that the lab modified. So in essence, you have injected the test subject with 10 billion of the same T-Cell. Unless the doctors have a way of massaging the genes on a representative sample of T-Cells, then this is kind of useless to the patient. What good are 10 billion T-Cells if they are each only good for tagging one antigen? Meaning, that the 10 billion T cells could only respond to a single stimulus, i.e. they could all only fight one strain of the common cold, but not anything else.
Disclaimer: I have a BA in bio from a public ivy; however, my GPA wasn't that great, and I didn't pursue a career in the field. I very well could be overlooking something substantial in immunology etc.
Unanswered questions (Score:3, Informative)
Alas, I have enough biology to have questions not answered in the short article, but not enough to extract the answers from the referenced paper. (I did notice that the news article was slightly incorrect on one point. They are not actually 'clipping out' the CCR5 gene. They cause a break in the gene which gets imperfectly repaired, so that the gene becomes nonfunctional.)
Are these T cells capable of 'reproducing' and having an unlimited number of descendants? This is not the case for many types of cells - it is part of what makes stem cells special. The paper refers to T4 cell lines, which suggests that they can indefinitely reproduce.
If the treatment works, how long will it last? (If the answer to the previous question is 'no', the answer to this one will likely be be 'about as long as the lifetime of a T cell.' If the answer to the previous question is 'yes', the answer might be 'for a lifetime.'
Do the modified T cells have to come from the patient? If not, the treatment will be much cheaper: Do the extraction and genetic modification once, breed up a big batch, treat dozens of patients. If not, you need to do the genetic modification once for each patient.
Once you have a bunch of immune T cells, will they be able to eliminate HIV from the body? (I suspect not: I understand that as a retrovirus, HIV is very good at hiding dormant for a long while.)
The answers to these questions are the difference between this being a laboratory curiosity and this being the elimination of HIV in developed countries within 5 years.
Re:bravo (Score:5, Informative)
Actually, this is far from the truth. I am an HIV-positive individual and based on the fact that my HIV was detected early and also that I started on HIV medications within the first year of contracting it my lifespan has been extended to the point where I will most likely live a full life. Before contracting HIV I thought it was a terrible thing to have and that I would kill myself if I ever got it. I have news for you: it is a terrible thing, but just like everything else in the world you get over it and with HIV medications having nearly NO side effects and once-to-twice daily dosing it makes life worth living.
While some may speculate on whether or not I really know what I'm talking about, I do. I am a healthcare professional. For those of you who are wondering why I didn't post this under my account, I would rather not taint Google's results with gossip for my next employer. :)
Re:Mod parent down - didn't RTFA (Score:1, Informative)
There are a lot of deadly viruses that could be cured by this.
Re:Potential Failure RIsks: (Score:2, Informative)
It sounds like what they're thinking of doing is more like: (1) draw up 10 billion T-Cells, (2) use an enzyme to cleave off the CCR5 proteins, (3) filter out the enzyme+proteins, and (4) reinject the T-Cells. Ie, I don't think issue 3 would crop up (or, at least, it'd be much more limited in scope). The real issue, as I see it, is that those 10 billion T-Cells will eventually die. Not knowing enough about how proteins on the cell membrane are created/carried over during mitosis, it'd seem the biggest issue is that those 10 billion T-Cells are likely to either duplicate and regenerate the CCR5 protein or simply die out before the HIV is eliminated. Either situation would seem to only delay the spreading of HIV in the body.
On the other hand, if it happens that the CCR5 protein isn't regenerated, then perhaps HIV would be cured, but you'd be at risk of redevelopment a random assortment of childhood illnesses (which should just mean revaccination). Unfortunately, I don't know nearly enough about T-Cell reproduction and HIV to know exactly how it is HIV manages to permanently kill off T-Cell production.
Re:Unanswered questions (Score:5, Informative)
T cells are produced by the bone marrow. They don't reproduce on their own.
The lifespan of an average T cell is on the order of 10-20 weeks. I believe. Shorter in HIV patients.
Who knows? But not necessarily. After all, you get plenty of foreign T-cells with a blood transfusion. But I don't think anyone is necessarily viewing this treatment as a 'cure' in itself.
That's not known. But they've done it [telegraph.co.uk], with positive effects. Note how 'cure' is put in quotes, as it should be.
That is ridiculous. It's neither.
Re:CANCER (Score:5, Informative)
For the most part, T-cells die off naturally.
People infected with HIV do not have to deal with a problem of too many t-cells, so in this case it's not much of a concern.
Most importantly though, T-cells do not replicate to create more T-cells. They come from a type of lymphocyte starter cell (a stem cell essentially), which reproduces in the bone marrow.
Taking t-cells from your body, and then reintroducing them to your body will not give you leukemia (literally meaning "White Blood", refers to various cancers of white blood cells).
More than likely this is just a test, not *the cure*. The point being to see if the modified t-cells survive long enough to keep the count from dropping (as it would via a normal HIV infection). If it does work, then we can start developing methods to modify bone-marrow in order to make the new t-cells your body creates have the altered gene.
Of course, I'm not an expert, and the article is unfortunately slim on details, so this is basic speculation.
Re:might as well guinea pig at that point (Score:5, Informative)
Re:Potential Failure RIsks: (Score:3, Informative)
I don't think 1 will be a problem. All T Cells have a CCR5 membrane protein, but the HIV resistant ones have a mutant type CCR5 protein. CCR5 is the way in which T cells get infected by HIV, and people with mutant type CCR5 genes survive quite well.
2 may be a problem, and I think will be the biggest hurdle here.
3 Shouldn't be a problem. Zinc Finger nucleases are able to delete the genes from a bunch of different cells at once. The idea is that you get a whole lot of T-Cells, Remove the 32 base pair segment from the two copies of the CCR5 gene in each T-Cell using zinc finger nucleases to make them the HIV resistant mutant type, culture more T-Cells which should be HIV resistant since they have the mutant gene, and inject the T-cells back into the patient.
Re:might as well guinea pig at that point (Score:1, Informative)
CCR5 **delta 32** (Score:3, Informative)
Indeed. They seem to be trying to modify CCR5 to be CCR5 delta 32, which is the variant which is less prone to HIV (but not immune). The nonfunctional aspect is very important, as you wouldn't want to simply engineer a foetus to have this gene instead of normal CCR5 genes. From wikipedia:
Re:confused (Score:3, Informative)
Re:might as well guinea pig at that point (Score:4, Informative)
There are lots of engineers involved. My father ran a small medical startup some years ago and they made a very high tech (for the time) artificial ventilator that used rapid pulses of air rather than the typical high pressure slow pulses. They did lots of experiments on animals and had to jump through all kinds of hoops with the FDA just to be allowed to put the ventilator on a human subject. Essentially the only way, after the animal trials, to get the ventilator on a human patient was for the patient to be unresponsive to conventional treatment, at significant risk of death without intervention, and received signed autorization from the patient or guardian. (get those living wills drawn up and signed if you haven't already!)
It took years, huge personal and venture capital investment, and eventually the company was bought out and I think the techology disappeared or otherwise got incorporated into standard ventilators. I posted this to illustrate all the work that needs to go into a medical device before it is allowed to be tried on humans... and even then, promising, even successful technology does not always make it in the marketplace. Believe it or not, Doctors are some of the *worst* luddites around and it is incredibly difficult to get enough momentum for a new technology to take hold.
Re:might as well guinea pig at that point (Score:5, Informative)
You could be worse off, as the study may require that you go off the regular HIV cocktail you are taking to suppress it.
They would find it hard if not impossible to get ethical approval for that kind of study. If an effective treatment exists, controlled trials are controlled against that, and not against a placebo.
Re:might as well guinea pig at that point (Score:3, Informative)
Re:Potential Failure RIsks: (Score:3, Informative)
Re:Mutations (Score:3, Informative)
>What's to keep the virus from mutating and avoiding the CCR5 requirement it currently has?
The virus uses the CCR5 receptor as its binding and entry point into the cell [wikipedia.org]. There are other receptors it might/may use, but CCR5 is the predominant one, especially early in the infection. As such, it's the gateway: if you can block it, that massively reduces the viral effectiveness.
The process of developing a treatment for a disease is finding something the disease absolutely needs and targeting that. This is very difficult with HIV because, as you say, it has a high rate of mutation, but (as the wikipedia article says) at least in lab tests if you block CCR5, HIV infection drops by orders of magnitude -- so apparently, finding another route of entry is sufficiently complicated that it's highly unlikely that an otherwise viable mutation will evade this requirement.
And it begins... (Score:2, Informative)
Re:might as well guinea pig at that point (Score:2, Informative)
If you understood anything at all about the HIV virus you would not promulgate this insipid argument. HIV is a retrovirus-it writes itself into your DNA, and you can't truly get rid of it (at least, not with today's technology). Don't let reality get in the way of your paranoid conspiracy theories.