http://www.pbs.org/wgbh/evolution/library/10/4/l_104_06.html
Could someone tell me why this news isn’t publicly that well known? Wouldn’t you think lots of major pharmaceutical companies would spend lots of money trying to find a way of disrupting the protein and therefore find a cure for HIV?
Yes, I would think that. And, in fact, they are. Straight from the top of your linked page:
Um, from your cite: “This discovery has not yet translated into new treatments. A dozen pharmaceutical companies, however, are developing drugs designed to block HIV’s entrance into the white blood cell by creating a non-functional CCR-5 receptor. Already, some of them are in clinical trials in HIV patients, perhaps laying the groundwork for the most effective treatments yet.”
So, in other words, lots of pharmaceutical companies are spending lots of money trying to find a way to disrupt the protein. What was your question again?
I also note that this information is at least 5 years old, maybe it’s a dead end, or at least it’s taking longer than they thought.
Well yeah basically, I thought the news was quite old and the scientific community might have had some updates about it by now but not so, so I was hoping some of you guys knew.
Always remember - Google is your friend. I just googled CCR-5, which is mentioned in the article you quoted. A very techy article concerning it is http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601373 ; I don’t claim to understand more than 50% of it (if that), but it has a number of recent cites.
This one is in my wheel house. Much of my work has been, and continues to be in chemokines and chemokine receptors, though not in HIV.
First of all, five years is the blink of an eye in scientific research terms. You would barely have your reagents generated yet. People see science experiments in movies, and think that there is an “AHA!” moment that happens once a week. More often, it’s months and years of absolutely nothing going right. Five years? I wouldn’t expect to see any clinically relevant data (and we’d be talking VERY preliminary) for another five, and that’s if everything went perfectly.
Blocking CCR5 is tricky business. First of all, the cells that express CCR5 are quite mobile. So, it’s not like getting a drug into a localized organ, like a cortisone shot. The immune cells are constantly moving all over the body. Second, I’d be worried about toxicity. It isn’t like CCR5 is just hanging out on cells for use as an HIV receptor; it’s a functional molecule involved in cell migration. Blocking CCR5 could have unintended consequences on immunity.
That being said, there are tons of published experiments in this field. The most advanced, I believe, is a molecule called AOP-RANTES . RANTES, in addition to being the most forced acronym in the history of mankind (Regulated upon Activation Normal T cell Expressed and Secreted), is a ligand (it binds to) for CCR5. AOP-RANTES is a chemically modified version that inhibits CCR5. In that way, it AOP-RANTES, which inhibits CCR5 access, would seek out CCR5 and specifically bind to, and inhibit it. Thus, blocking HIV entry. Pretty neat.
But, as I said, there is TONS of research to go. It ain’t the movies. I myself have published a few papers showing ways to shrink tumors in mice, but that doesn’t mean that I’ve cured cancer!
FWIW, one of the newer anti-HIV drugs, T-20 (fuzeon), works in a similar fashion (binding to gp41, a virus envelope protein). IIRC, it is actually the gp120 protein that binds CCR5. gp120 binding is a hot area of research. It is generally more preferable to target the virus, as host cells easily regenerate their surface proteins and there are a lot more of them than the relatively small amount of virus around. Unincorporated viruses cannot regenerate their envelope proteins.
This is only one of several new classes of antiretrovirals currently under hot development. Integrase inhibitors as well as better drug-profile NRTIs, NNRTIs, and PIs are right over the horizon as well. And now we have Atripla! 10 years ago, some of the first HAART regimens were over 40 pills in a day, dosed at 8 or 10 different times, some on full stomachs, some not, some on different full stomachs. Not to mention all the work that went into the development of the first PIs. Now we have a one pill, once a day medicine. We’ve come a very, very long way.