Bone marrow transplant cures hiv infection

[freewillie99]

I'm sure I've seen this story on here before, but here's an update from today's WSJ.  Obviously getting a bone marrow transplant in order to eradicate HIV is unrealistic to say the least, but it looks like this may indicate gene therapy approaches have some merit.

http://online.wsj.com/article/SB122602394113507555.html?mod=googlenews_wsj

[John2038]

Since the beginning, got lot of hopes in the approach of the Dr Hutter and on the VRX496.

Finally, I should stop listening to the pessimist, despite my respect for them.


Just a fantastic news  !

[ronaldinho]

So, the next step would be to find a way to alter genetically the immune system of an HIV+ patient without having to recur to a bone marrow transplant. Hope scientists can work this out.

[HALOO]

Have a Question, Do you test Postive or Negative??

[HALOO]

I am sorry, I mean he(the Patient)

[freewillie99]

So, the next step would be to find a way to alter genetically the immune system of an HIV+ patient without having to recur to a bone marrow transplant. Hope scientists can work this out.

ronaldinho:

Correct.  Here's the latest about the work being done at California's "City of Hope" that is referenced in the WSJ article.

http://www.abnnewswire.net/press/en/58361/Benitec_Limited_ASX:BLT_City_of_Hope_Human_Trial_Update.html

[freewillie99]

Here's another article which was posted here a couple months back for those that are new or just didn't see it.  It's along the same lines as the Benitec project at City of Hope and somewhat related to the work being done by Virxys in Maryland as well as on the patient in Germany referenced above.  My point here is not necessarily that any of this is going to result in imminent treatments, but to show that there is promising work being done on the gene therapy front and reason for optimism.

http://www.webmd.com/hiv-aids/news/20080808/gene-silencing-may-stop-aids-virus?page=2

[leit]

Very probably, we will soon know every detail: "Dr. Hütter is writing an article for a specialized medical journal in order to describe and make his therapy public in every detail".

http://www.repubblica.it/2008/11/sezioni/scienza_e_tecnologia/aids-guarito/aids-guarito/aids-guarito.html - last paragraph

[MYSTERY]

 
 Dr. Andrew Badley, director of the HIV and immunology research lab at the Mayo Clinic in Rochester, 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."

[freewillie99]

Leit: Thanks for the link to the article.  Too bad I don't read Spanish...

Re: Dr. Andrew Badley of the Mayo Clinic's quote in the above article, sounds like a case of "not invented here" sour grapes.  Nevertheless, I look forward to extensive peer review and exploration of this exciting (and presumably) groundbreaking case.

edit: or is it in Italian?

[georgep77]

Yes freewillie99, is in Italian.

Hopefully the article can be translated to english, using google translator

http://www.google.ca/language_tools?hl=en

                                                     

[tash08]

For example, Dr. Irvin S. Y. Chen, director of the AIDS Institute at U.C.L.A. , is working on using RNA “hairpin scissors” to cut out the bits of genetic material in blood stem cells that code for the receptors. The concept is working in monkeys, he said. Eventually, he hopes, it will be possible to inject them into humans after wiping out only part of the immune system with drugs. “I think that would carry no risk of death,” he said.

http://www.nytimes.com/2008/11/14/health/14hiv.html?_r=1&oref=slogin

[John2038]

Either a cure or a path to it

Im volunteer to do it and will ask to be treated also.
no matter if it fails for 20-30%

Otherwise video about the subject
http://www.youtube.com/watch?v=0ZNtePGaJWw

[Miss Philicia]

I'd rather take a handful of pills every day for decades than volunteer for something with a 30% chance of failure.

[John2038]

Just wondering why they haven't talk about his cd4, cd4%, fbc, etc

[OneTampa]

This is a very interesting development.  I was curious though when it was reported on Fox news the other night and only given about 15 seconds.  There was no "breaking" news or interview with the doctor.  That made me a bit suspicious.  For one thing, if this type of information doesn't deserve the "breaking news" crawl, I don't know what does.

[ronaldinho]

This is a very interesting development.  I was curious though when it was reported on Fox news the other night and only given about 15 seconds.  There was no "breaking" news or interview with the doctor.  That made me a bit suspicious.  For one thing, if this type of information doesn't deserve the "breaking news" crawl, I don't know what does.

The absence of press highlights also made me wonder. This story has going on for almost 2 years with little press coverage. Maybe they wanna be sure that the outcome of this transplant was not due to an extraordinary rare conjonction of circumstances, so they will wait for another HIV + patients who are in need of bone marrow transplant to undergo the same procedure, so they can be sure that the procedure itself is capable of eradicating HIV, regardless of some other unknown specific genetics of donor and receptor that might have played a role in this case.

[John2038]

There are a huge amount of website covering this event.
Some are scientifics website, others are websites from newspaper, etc

Just take a look for e.g. here and see how many websites are referenced accross mutliples pages

[freewillie99]

I was curious though when it was reported on Fox news the other night and only given about 15 seconds.  There was no "breaking" news or interview with the doctor.  That made me a bit suspicious. 

Hmmm...OneTampa, please consider the source.  Fox News?  The home of Sean Hannity, Bill O'Reilly, and the legion of Barbie newscasters?  Fox thinks Sarah Palin was highly qualified to be President.  Enough said.  Somehow I don't see them being overly concerned about anything related to gays or HIV unless it's negative.  Far be it for me to tell you what to do, but you might consider alternative sources of information.

[David Evans]

Hello everyone,

I wrote an article about this for AIDSmeds earlier this year: http://www.aidsmeds.com/articles/hiv_aids_stemcell_2042_14199.shtml.

I interviewed Huetter for the article and talked to a number of other people at the time, and you're right that general awareness of the transplant was fairly low. It is possible that Huetter's using the "C" word a bit incautiously, but he and the transplant patient are legit, and there's a decent chance that a functional cure may have been acheived.

Experts were mixed about how relevant this would be for the average person with HIV, and everyone at that time pointed at gene therapy. That's some years off in the future, but it's hopeful.

David

[OneTampa]

Freewillie99, oh yes.  I am quite cautious about Ms. Fox.  I was in DC and watched the local news broadcast.  I will check out other sources though.

[John2038]

What surprise me a bit about this patient result, is that he is not the only HIV poz guy who have been through a chemio.

So why this result haven't been obtained earlier already ?

Is it only due to the use of homozygote CCR5 delta 32, is it due to a different chemio protocol, to the chance, etc ?

Why no more details have been published, in particular, the cd4 and fbc, is the patient virus a R5 only or is it mix, etc

This news contains little info to support the hope it provide

[leit]

Why no more details have been published, in particular, the cd4 and fbc, is the patient virus a R5 only or is it mix, etc

Don't expect from the WSJ or Fox News what they can't give, "John2038", and see above: "Dr. Hütter is writing an article for a specialized medical journal in order to describe and make his therapy public in every detail".

Moreover, after the recent amfAR meeting, Dr. Hütter has promised to send some biological samples of his patient's to U.S. researchers (Dr. Ho and others - sorry but I don't manage to find the source where I've read that), so they can study them too.

[Assurbanipal]

What surprise me a bit about this patient result, is that he is not the only HIV poz guy who have been through a chemio.

So why this result haven't been obtained earlier already ?

Actually, the WSJ article suggested that this was the second patient to have been potentially "cured" of HIV, --  with a previous patient who did not survive the cancer treatment but did not show presence of HIV anymore. If a rare genetic immunity is required in the donor cells it isn't really surprising that this would be the first to survive both. While chemo is pretty common, bone marrow transplants aren't that frequent....  and doctors tend to prefer to do transplants on people who have the greatest chance of living after the operation ...

[John2038]

Sure leit, but they could have at least publish some data last Feb (CROI 2008)
It's the second announcement (300 and 600 days) without detailed publications.

Anyway, I still think that it's either the cure or a path to it.

I also think that all those scientist who are working since years for a solution to HIV are looser.
The approach of the Dr Hutter is so obvious (and many others approach are) but big pharma just prefer produce pills able to almost keep chronic this disease.

I know it's not fair to talk like that, but an immune system reset was one of my question 1 year ago.
If I can ask myself about such approach, any body can.
Same with starting HAART earlier and so many others things I just forget.

It seems that for all these people and most patient, be cautious is the only way of thinking.
For them, nothing is obvious in medicine, even what is logical.
It make sense generally speaking (the body is not a computer), but thinking about resetting the immune system should have been tried much earlier.

[John2038]

Just this nice short summary on what have been said so far about this subject.

Several newspapers recently profiled the case of an HIV-positive person who underwent a bone marrow transplant to treat leukemia and who has had undetectable HIV viral loads for almost two years. For the procedure -- performed by German hematologist Gero Hutter of Berlin's Charite Medical University on a 42-year-old American living in the city -- the patient's bone marrow cells were replaced with those from a donor with a naturally occurring gene mutation that provides immunity to almost all strains of HIV by preventing the CCR5 molecule from appearing on the surface of cells. Prior to the transplant, Hutter administered a standard regimen of drugs and radiation to kill the patient's bone marrow cells and many immune-system cells, which may have helped the treatment succeed because the procedure killed many cells that harbor HIV, according to an earlier Wall Street Journal report. Transplant specialists then ordered the patient to stop taking his antiretroviral drugs when they transfused the donor cells because they were concerned that the drugs might undermine the cells' ability to survive in their new host. Although the plan was to resume the antiretroviral regimen once HIV re-emerged in the patient's blood, more than 600 days later, standard tests have not detected HIV in his blood, or in brain and rectal tissues where the virus often hides (Kaiser Daily HIV/AIDS Report, 11/7). Summaries appear below.

    * New York Times: According to some U.S. researchers, the treatment has "novel medical implications" but will ultimately "be of little immediate use" in treating HIV/AIDS, the Times reports. Anthony Fauci, director of NIH's National Institute of Allergy and Infectious Diseases, said the treatment is "very nice" and "not even surprising," but "just off the table of practicality." The Times reports that many researchers said the treatment is "unthinkable" for the millions of people living with HIV/AIDS in Africa and "impractical even for insured patients in top research hospitals." The patient had leukemia in addition to AIDS, which warranted the high risk of a blood stem cell transplant, but 10% to 30% of people who receive bone marrow transplants die. According to the Times, the odds of locating a donor who is both a good tissue match for the patient and has the CCR5 genetic mutation are "extremely small." Robert Gallo, director of the Institute of Human Virology at the University of Maryland School of Medicine, said, "Frankly, I'd rather take" antiretroviral drugs. However, the Times reports that the success reported for this patient is "evidence that a long-dreamed-of therapy for AIDS -- injecting stem cells that have been genetically reengineered with the mutation -- might work" (McNeil, New York Times, 11/14).

    * AP/Google.com: Although researchers and the physicians involved in the case caution that it "might be no more than a fluke, others say it may inspire a greater interest in gene therapy to fight the disease that claims two million lives each year," the AP/Google.com reports. Although the patient 20 months after the procedure has not shown signs of the virus, Andrew Badley -- director of HIV and immunology research at the Mayo Clinic in Rochester, Minn. -- said the tests that determine the patient's HIV viral loads likely have 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. Fauci said the procedure was too expensive and dangerous to use as a first-line therapy. However, he said it could inspire researchers to pursue gene therapy as a way 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, added that gene therapy as inexpensive and effective as current drug treatments is in the 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," he said (McGroarty, AP/Google.com, 11/13).

    * Reuters: Hutter and his team said that although they have not been able to find any traces of HIV in the patient, it does not mean he has been cured. "The virus is tricky. It can always return," Hutter said. According to Reuters, the researchers said that bone marrow transplants could never become a standard HIV/AIDS treatment because the transplants are "rigorous and dangerous and require the patient to first have his or her own bone marrow completely destroyed." In addition, the procedure can be fatal because patients have no immune system until the stem cells can grow and replace theirs, leaving them susceptible to even minor infections (Reuters, 11/12).

    * Deutsche Welle: According to physicians at the Berlin hospital, they are continuing to monitor the patient's health and are prepared to put him back on antiretrovirals if the virus reappears. Thomas Schneider, Charite's director of infectology, said, "We cannot say with certainty that the virus won't begin replicating itself in the future," adding, "But the mere fact that it hasn't yet done so is a minor sensation" (Deutsche Welle, 11/13).

[leit]

I also think that all those scientist who are working since years for a solution to HIV are looser.
The approach of the Dr Hutter is so obvious (and many others approach are) but big pharma just prefer produce pills able to almost keep chronic this disease.

I agree. As I recently wrote to a very smart friend: "IMHO, the "year of the big mistake" was 1997, when David Ho's theory about eradication by HAART in 2-3 years failed and Siliciano/Fauci/Richman calculated that about 70 years of complete virus suppression (not realistic!) were needed to eradicate HIV. Well, AT THAT TIME they should have dropped out HAART (big pharma would however have kept working on it, as it happened) and search for a REAL CURE. They didn't do it, and we are now taking the consequences."

It seems that for all these people and most patient, be cautious is the only way of thinking.

I don't believe I HATE HIV less than you do, "John2038". Nevertheless, I wouldn't like to switch from HIV to cancer or some other disaster. As you perfectly know, the immune system is incredibly intricate and delicate, and little is known about it. Moreover, gene therapies are far from being an usual practice (think about bubble boys' "success" and then... leukaemia).

[leit]

Dr. Sax's opinion: http://blogs.jwatch.org/hiv-id-observations/index.php/2008/11/10/yes-just-a-case-report-but-incredibly-cool/.

[John2038]

I don't believe I HATE HIV less than you do, "John2038". Nevertheless, I wouldn't like to switch from HIV to cancer or some other disaster. As you perfectly know, the immune system is incredibly intricate and delicate, and little is known about it. Moreover, gene therapies are far from being an usual practice (think about bubble boys' "success" and then... leukaemia).

What about all those people who have die from HIV ? If some of them have got such treatment as an option, instead of nothing, maybe some of them will have live longer, and maybe the way of doing chemo will have improve so much that the death rate will have significantly drop to become a possible treatment (which doesn't necessarily would have involve chemo, but any others safe ways the research might have found since).

The Dr Hutter approach is the second one I know to have been documented in the past 25 years.
After so many deaths, it's an extremely very rare event. Thanks for him to be a hematologist, and not one of these incompetent or cautious ID doc.

Some ID doc are definitely great, the vast majority don't even know better than you what could be your next combo.

In the long list of the things that upset me in the management of this disease, the last one is about the drug to choose.
Isentress is an integrase inhibitor. Compared to the others drugs, it is working at the very beginning of the virus replication cycle. And not surprisingly, it is one of the best ever HIV drug never created.
It seems so obvious to me that consequently, this drug should be prescribed in first line regimen, if it is financially possible. But if you talk to your ID doc about starting with it, he will very probably be willing to start with a much more conventional regimen, just to stay in the comfort zone, without any money consideration. For me, we have accumulate already enough data about Isentress to decide to use it in first line regimen, and without having to remain as usual extremely cautious.

[John2038]

Not a good news, but nothing we don't know, unfortunately

http://forums.poz.com/index.php?topic=20441.msg306544#msg306544

[NewYorkKat]

I agree with John2030. USE ME AS A GUINEA PIG!!!

20-30% failure is a lot better than 50 to 70%!



When I had lasik done, I said I wanted both eyes instead of one. I risked it and now my vision is 20/20.

Anything to rid of this thing!

[NewYorkKat]

Excuse me John2038. My vision is fine but my memory fades....

[John2038]

Ohh NewYorkKat, lets do it together

[blondbeauty]

The news is interesting in the field of HIV research. But as I have posted in the Spanish forum, transplant is not the best solution for the following reasons.
1) You have to find a compatible donor.
2) The donor has to be compatible and immune to HIV. The chances of this to happen are less than winning the lottery.
3) It is safer, easier and much more effective to take antirretrovirals than taking immunosuppresors to accept the transplant.

[hahaha]

I have a feeling that probably transplant is the only solution for "cure" in the near future.
There are 4 reasons"
1. a cure  need to source out and delete most of the CD4 and other reservoir that are infected.
2. a cure need to "refresh" and "recover" CD8's memory for its impair function.
3. a cure need to fix the problem that the clean CD4 remain unattacked.
4. a cure need to  come out with a complicate immune function (including the complicate interaction between all kind of white cell, B cell, dentritic cell, brain) that is capable of fighting HIV.

Due to the transplant, most of the "bad reservior" has been x-rayed and killed, so 1 has been solved.
the transplant will create new born CD8, that the fuction has not been impared. 2 then solved
the transplant of CCR5-defect cells protect CD4 unattacked.
the transplant will again, creat new cells (B cells...) that fight back HIV.

If the quantity of transplant of cell is large enough, it will ceate a envioroment similar to a healthy person just being infected or attacked by less than 3000 HIV. which may lead to a good possiblity that the body may kill HIV easily and remain uninfected.


Just a wild guess for fun, don't take it serious.       

[freewillie99]

This post was deleted due to unnecessary rudeness. 

[John2038]

I always wonder why people force themselves to not live in a better world, avoiding for e.g judging others.

hahaha, the good idea in your approach is that by enumerating the different steps that might lead to a cure, we can then review them to see if for each step, it exist alternate safer ways, for e.g

About what you said, at least you have tried to propose, and that's always a good things

[David Evans]

Hi folks,

Let's watch the insults. If someone posts something that doesn't make sense for some reason - and you know why they aren't making sense, either ask further questions or provide the info they're missing. We're all just trying to educate one another.

In terms of hopes about the transplant, as I've said before hope is a great thing - it's vital. But it also makes sense to try and place our hopes where they have the greatest chance of becoming reality. I don't think anyone can say with 100 percent certainty that we'll never try this on people who don't otherwise need a stem cell transplant (i.e. for cancer). There are, however, some legitimate arguments against it - and bringing them up doesn't mean that a person is trying to destroy another person's hope. It's just acknowledging the obstacles that exist.

First of all stem cell transplants are dangerous - as others have said. Up to 30 percent of people who have them done die within days or weeks of the procedure. That's a very high rate of death. Because of this (before we ever get into the issue about costs) it is likely that the only candidates who would be deemed ethically acceptable would be those people who have not only failed all antiretroviral (ARV) drugs, but who are also very ill and at high risk of dying in the near future. It's just basic medical ethics. As sucky as it can be to live with HIV, and to deal with the the ARVs, no ethical doctor would would take that risk with someone who had other, less risky treatment options.

Then there's the cost. Right now, in the United States, some insurance companies still refuse to cover the cost of stem cell transplants in people with just cancer. They claim it is still "experimental." The costs can run well over $200,000. Granted, if a person was truly cured, then the amount saved from not being on life-long ARV therapy would be greater than $200K - but it will likely take a high rate of successes in people w/both HIV and cancer before payers would mostly likely even consider covering the costs.

-David

[John2038]

David,

there are still at least 3 questions.

1) We know that this procedure is especially dangerous just after the transplant, until the immune system is becoming enough strong to protect the patient again.

So isn't the problem just related to the efficiency of the bubble room ? (at least, we can transpose the problem there)
If so, isn't it something we can improve (assuming no others problems for the transplant, such as its rejection, etc)

2) Can transplant ourselves, after a washing procedure ?

3) What would be the mortality rate if a chemio + transplant is made in someone almost healthy, instead of in the terminal stage of the disease ?

[leatherman]

3) What would be the mortality rate if a chemio + transplant is made in someone almost healthy, instead of in the terminal stage of the disease ?

every time I see the threads about this issue, I have two thoughts:

first, what effect did the leukemia have on this patient's treatment outcome? Does this only "work" if you have leukemia in conjunction with HIV? would you still have these results with a different illness, or with no illness?

second, chemo is not something to be taken lightly. It is a very harsh treatment and quite a number of people do not survive this treatment; and of those that do "pull through", it's often after months and months of intense sickness, hair loss, etc. I don't have any knowledge about the side-effects of a bone marrow transplant, but I would imagine that it comes with it's own set of lethal problems too.

----------------------------------------------------------------
Just my personal thoughts about this kind of treatment and it's effects:

I would suggest visiting the oncology floor of your local hospital before considering this a viable kind of treatment. Having spent almost 60 days on that floor with my partner earlier this year and seeing the other patients (without the complication of HIV) come and go (and many who left did not go home but went to the morgue), I would be hard pressed to have chemo on myself if I found out I had cancer along with my AIDS.

Didn't I read that one of these "cured" patients died a few months later anyway? My partner had AIDS and non-Hodgkins lymphoma. After going through 2 rounds of chemo which did not work against the cancerous tumors, he passed away a month later. I still have unresolved feeling about the suffering we and the doctors put him through before his eventual death. Dying is bad enough without suffering from the "treatment" at the end.

Actually seeing what I did in those months, I would not go through chemo for any reason at this point in my life. right now, living with HIV is hard enough - and I'm at a stable level - without adding leukemia, chemo, marrow transplants, and all the side effects from those, just on the off chance of being "cured" if I lived through it all.

mikie
who is just not enough of a gambler to be a guinea pig

[John2038]

leatherman

you are one of the great guy in this forum. You have been through so many things. But still nice and polite. What you are saying must make sens, despite that in the bottom of my heart, I could potentially do whatever it take to get ride of this virus. Should I die, I will have kill it.

But you make me think a bit more.
I will travel to EU next month, and I was willing to contact the Dr Hutter, to discuss with him the possibilities, odd to survive and so. And if he agree, if I agree, and if the cost can be covered by a special fund, I might try.

I don't find it funny to survive to this bug, waiting the next combo, hoping the cure, despite I never got real symptoms, still out of meds, healthy, but already multi-resistant.
Yep, got a happy life, still.

But if the odd to survive could become much higher (such as 95% +) cause of my good health right now, I think it's something to try.

On the other hand, your advices based on your experience are important too.
Thanks !

Note
Yep, not the place to talk about feeling. But taking such decision is still in the scope of this thread I guess.

[leatherman]

not the place to talk about feeling. But taking such decision is still in the scope of this thread I guess.

I understand; however I thought because some people discussed utilizing the actual procedure, that a discussion of the possible ramifications would be appropriate.

Similar to the way some of the general population view HIV as an easy illness now ("chronic and manageable". and no, I'm not discussing the truth of that statement, just pointing it out as a general opinion in the public arena), seeing people bat the word "chemo" around like it's an easy treatment made me want to point out that just surviving the chemo is a huge feat in itself and shouldn't be minimized when looking at this scenario for a "cure".

Just like the issue with leukemia. If that's the route to this "cure", would you really want to get leukemia and deal with those issues to finally reach the ultimate "cure"? Each person would have to make his or her on judgement call on that based on health status and other criteria. Having been as sick as I was, I've already had to evaluate what sort of treatments I'm willing to take in relationship to quality vs quantity of life. (there's a lot of stuff, I won't do: I won't take meds if I have to throw up again EVERY day; I won't do chemo for cancer because I don't think my health is good enough and I'm prejudiced against it after seeing what I saw in the hospital) With Jim, we made those same decisions. I saw several older men in the oncology dpt also make that decision, and go home to some quality of life rather than quantity (and only "possible" quantity if the treatment actually worked. no guarantee given for that though).

What you are saying must make sens, despite that in the bottom of my heart, I could potentially do whatever it take to get ride of this virus. Should I die, I will have kill it.

I was willing to contact the Dr Hutter, to discuss with him the possibilities, odd to survive and so. And if he agree, if I agree, and if the cost can be covered by a special fund, I might try.

I don't find it funny to survive to this bug, waiting the next combo, hoping the cure, despite I never got real symptoms, still out of meds, healthy, but already multi-resistant.
Yep, got a happy life, still.

But if the odd to survive could become much higher (such as 95% +) cause of my good health right now, I think it's something to try.

I don't suggest not checking into this though.  I know that you're quite intelligent and informed. I even agree with your notion that more "thinking outside the box" might find the road to the cure. On one hand, this procedure just looks like a last very desperate attempt, which unfortunately has meant that it's been performed on patients who had low odds of survival even before this radical of a treatment. On the other hand, risking this sort of treatment on a healthy person has a slew of ethical implications, so it will probably be very difficult to get results based on someone with better health.

Perhaps more will be learned from this though, and more knowledge definitely will lead to a cure.

[John2038]

leatherman

you have well describe how it might be to be part of the 30% of people for who this treatment might/have failed.

Now, this procedure is supposed also to work for the 70% remaining.
For those people, if this treatment lead to a cure, no more drugs, no more worries, normal life, almost.

Those who have died in the 30% have die of their cancer, not of HIV.

So the questions:

1) Can we better secure the period betw the transplant and the recovery of immune system ?
2) Can transplant ourselves, after a washing procedure ?
3) Will the mortality rate decrease if a chemio + transplant is made in someone almost healthy, instead of in the terminal stage of the disease ?

A positive to any of these 3 questions will provide better odds.

[Peter Staley]

Those who have died in the 30% have die of their cancer, not of HIV.

Not true.  Many died from opportunistic infections after their immune systems were wiped out by the procedure.

[John2038]

Hi Peter

my argument was that those 30% have died from the OI/non-OI they got diagnosed before the chemo (despite I just wrote cancer)

This to says : how much this percentage will be for those with HIV but without OI/non-OI before doing the chemo ?

Sorry for the shortcut.

[SASA39]

2 questions :
1.Doctors have statted that they`ve  done  a biopsy tests which has concluded that a famous "German patient" do not have HIV virus in his anal cells , liver etc, etc ...
But what about latent viral reservoir tissues such as brain , nerves , etc , etc ?
2."German patient" has inhereted CCR5 delta 32 mutation , that`s OK , but what if gp120 find a CCR4 mutation - or in other words in a case of dual tropism is he safe enough ?
edited for typo

[Peter Staley]

Hi Peter

my argument was that those 30% have died from the OI/non-OI they got diagnosed before the chemo (despite I just wrote cancer)

This to says : how much this percentage will be for those with HIV but without OI/non-OI before doing the chemo ?

Sorry for the shortcut.

You don't have to have a prior OI.  You can die from any new infection that occurs before the new immune system takes hold.  You can die from a new infection you get in the hospital, for instance.  The 30% death rate is for HIV NEGATIVE patients.  I'd imagine as pozzies, our rate would be higher.

[John2038]

Eish

I was assuming people were doing chemo only when they was having an OI/non-OI
So that the 30% apply to those who are having a cancer for example.

My guess: HIV shouldn't impact the chemo outcome if there are no pre-existing OI/non-OI.
Cause HIV is destroying the immune system, exactly what the chemio does, but radically.

Consequently, IMHO these 30% are the same for those coinfected or not with HIV.

Now, chemo haven't been tested on healthy people, or people almost healthy (HIV positive but controlling their infection, with no OI/non-OI).

As such, for those people, the odds to survive seems to be better than these 30%.

I do not say I am right, just an opinion, and I appreciate to be able to talk about it with people having better background than me.

[SASA39]

And answers to my 2 Q........................?

[David Evans]

Dear all,

I've actually been in the process of writing up a new Web Exclusive on this topic that will be up on the site Tuesday evening, but I'll weight in here in advance. I'm not a transplant expert, but I do know that the chemotherapy and radiation that is necessary for a bone marrow (i.e. stem cell) transplant is pretty radical and very toxic to the body, HIV present or not. For someone whose immune system has already been severely depleted by HIV infection, it can, in fact, be worse, quite a bit so.

Think about traditional chemotherapy for many other types of cancers. It is almost always done on an outpatient basis. The lymph ablation that occurs with stem cell transplants is so intensive that most centers only do it on an inpatient basis so as to be able to respond quickly to life threatening infections. Researchers, including those working on gene therapies for HIV, are trying to find safer ways to free up space for the new stem cells, but we just aren't there yet.

I've never been tempted by the gambling bug but I'd bet a lot of money that we aren't likely to start doing traditional stem cell transplants on people with HIV who don't otherwise need it. If the Berlin case does get well confirmed by outside researchers, it is most likely that this will be tried on other patients with leukemia and lymphoma first.

Hopefully by the time we've gotten more data from those additional cases, the gene therapy, RNA interference and zinc finger field will have progressed enough that they'll end up being more viable options. One of the benefits of using a person's own stem cells is that you don't have to find a good genetically matched donor - a process that's already challenging when you're not also trying to find a donor who can't make CCR5. This is even more vital when you're talking about the majority of the people on the planet who have HIV, who are of African descent, and in whom there are no such donors.

Unfortunately, when you're talking about infusing a person with stem cells, whether they're from their own bodies or someone elses, you still currently have to kill off most of the existing stem cells so that the new ones will take root and flourish. That means even with gene therapy, we're still talking about a course of potentially lethal chemotherapy and/or radiation - at least at the present time.

As the researcher I spoke to for the report said, they're intensively looking for ways to kill off those stem cells without destroying a person's immune system in the process. They've made progress with targeted antibodies in mice, but they've still got a lot of work ahead of them.

As I said before, I remain ever hopeful, but if there's one thing we've learned in this epidemic, and a principle to which the forums and AIDSmeds is dedicated, it's to become informed about all the risks and rewards about treatment before making big decisions. That doesn't make us pessimists, just that we are taking responsibility for our bodies and our lives.

I think the same is true when considering the implications of the Berlin transplant. At the very worst, we may find that there is still HIV present in the gentleman who got the transplant and that the improvements were temporary. Even then we'll have learned things that will move AIDS research forward. There's a good chance that the outcome will be more favorable than that, and the advances this could help propel in HIV research will be even larger. I think that's a very hopeful view to take. It's probably a bit early to argue about whether it's appropriate for people to undergo toxic chemotherapy and risk death for a possible cure. Instead, lets hope that by the time the research catches up with this Berlin case and becomes a reasonable option for more than a handful of people, the risks won't have to be so high.

Respectfully,
David

[SASA39]

Thank you David

[John2038]

Thanks David.


Sorry to insist.

We do not have data (success rates) on chemo made on healthy people.

The answer to this question can change the risk perception we have on this approach.

My 2 cents (of course, might be wrong): Having a leukemia or any others OI/non-OIs is just worsening the situation. Transplant of homozygote CCR5 is just a nice to have.

[freewillie99]

Thanks for the add, David.  Very interesting.

[freewillie99]

Here's an interesting article published in February of this year by "Oncology Times" detailing a potential treatment devised by a group at Stanford Medical School to "clear" existing stem cells and create a niche where new transplanted stem cells can take hold and grow.  Unlike traditional stem cell transplantation which uses toxic radiation and chemotherapy (see: the German patient), this much more benign and far less toxic approach uses a monoclonal antibody, ACK2, to create the niche. 

Obviously this is in it's infancy; it hasn't been tested in humans yet.  However, with a little bit of imagination you can perhaps see where the combination of a person's modified stem cells lacking a CCR5 receptor and this approach might take us.

http://www.oncology-times.com/pt/re/oncotimes/fulltext.00130989-200802101-00017.htm;jsessionid=J4rRQGTDNMd57SDQmQcLTl1B7ytNL4SYLsTmhcZvcXh2L2zHQzLC!976670012!181195629!8091!-1   

[NYCguy]

I know it's been talked about elsewhere, but apropos CCR5 don't forget that Sangamo Pharma is developing a Zinc finger technique that would supposedly turn off the receptor permanently with a simple injection or series of injections.  MUCH easier than a transplant. 

Unfortunately they have been 'planning human trials in late 2007' for a while and no new news as far as I have seen.

[freewillie99]

Sangamo Pharma is developing a Zinc finger technique that would supposedly turn off the receptor permanently with a simple injection or series of injections.  MUCH easier than a transplant. 

Unfortunately they have been 'planning human trials in late 2007' for a while and no new news as far as I have seen.

Evidently you missed it.  Dr. Carl June and his team at Penn have organized a Phase 1 trial which will be starting shortly. 

http://www.youtube.com/watch?v=1Ah8lZ4sZFw

[NYCguy]

saw that right after I made my post.  Glad they are moving forward - Sangamo has finally updated their site to say they are filing an IND in 2008.  I'm skeptical as to what 'soon' means, however.  But June is a good guy with good rep.  I like the concept.

[leit]

Dear friends,

My feeling is that all our hopes concerning CCR5 depend on three points we're taking for granted:
1 - that HIV was eradicated from Dr. Hütter's patient
2 - at the very least, that he was clinically cured for good
3 - that the points above depend only on (acquired) CCR5delta32 homozygosity.

Unfortunately, neither point 1 or 2 have been demonstrated (and I fear it will never be possible to do that but only, at best, to demonstrate that one point, or both, is false).
But the most serious thing is that there are studies proofing not only that CCR5delta32 homozygosity isn't enough to protect from infection, but even that CCR5delta32 homozygous people percentage is virtually the same in the HIV-infected and uninfected (see, for instance, "Homozygous Delta32 deletion of the CCR-5 chemokine receptor gene in an HIV-1-infected patient").

I'd like to know your opinions.

[John2038]

Exploring Gene Therapy To Fight AIDS

The apparent success of a case in which German doctors cured a man of AIDS using a bone marrow transplant comes as no surprise to Gerhard Bauer, a UC Davis stem cell researcher. Bauer has been working for more than 10 years on a similar cure for AIDS based on replacing the devastated immune system of an HIV-infected patient with stem cells that have been engineered to resist human immunodeficiency syndrome.

Bauer plans to present the preliminary results of his latest research at the 50th annual meeting of the American Society for Hematology in San Francisco on Sunday, December 6, 2008, from 6 to 8 p.m. at the Moscone Center. He and his UC Davis research team will present a poster detailing the development of a mouse model that allows pre-clinical testing of their new gene-therapy protocol, which they hope will pave the way for human clinical trials within five years.

"The case in Germany was a natural gene-therapy experiment," explained Bauer, an assistant professor of hematology and oncology and director of a good manufacturing practice (GMP) laboratory now under construction in the new UC Davis Institute for Regenerative Cures in Sacramento. "We are working on a similar approach to genetically engineer a patient's own stem cells in a way that mimics this natural immunity. The German case offers further proof that genetic engineering provides a pathway to success, and gene therapy offers real hope as a cure for AIDS."

Last month, German doctors reported that they had cured a 42-year-old of acquired immune deficiency syndrome, or AIDS. The patient, an American living in Berlin, also had leukemia, which is best treated by a bone marrow transplant. Thinking they might be able to cure the man of both diseases, the physicians gave him a bone marrow transplant from a person with natural immunity to HIV. The patient has now lived for 20 months since the transplant without any detectable traces of HIV.

To establish similar immunity in HIV patients, the UC Davis team manipulated human skin cells to give these cells many of the same properties as stem cells. These transformed cells, called induced pluripotent stem (IPS) cells, are capable of differentiating into, among other cell types, hematopoietic stem cells, which are normally found in bone marrow and are responsible for producing the various types of immune cells.

"If we can replace normal immune cells with HIV-resistant ones, we can cure AIDS," Bauer said.

Bauer and stem cell program research associate Joseph Anderson have developed several anti-HIV genes that they plan to insert into IPS cells using standard gene-therapy techniques and viral vectors (viruses that efficiently insert the genes they carry into host cells). These engineered IPS cells could then be differentiated into bone marrow stem cells and introduced into the patient using a procedure similar to a bone marrow transplant.

"The hope is that one day we will use a patient's own skin cells to develop the engineered IPS cells to avoid possible rejection," said Bauer, who worked on clinical HIV gene therapy trials at Childrens Hospital Los Angeles before coming to UC Davis. "As in the German case, the end result would be an immune system that produces HIV-resistant immune cells."

In theory, the experimental treatment would result in an immune system that remains functional, even in the face of an HIV infection, but would halt or slow the progression toward AIDS.

"The anti-HIV genes take advantage of how HIV works," added Anderson, who is now writing a paper about the investigation. "The virus targets cells that are descendants of hemopoeitic stem cells."

During the first stages of infection, HIV targets macrophage cells, gaining entrance into the cell by binding to a receptor called CCR5 on the cell's surface. Later in the infection it targets CD4+ T cells, binding to the CXCR4 receptor on the surface of these cells and bringing on full-blown AIDS.

What researchers discovered is that there is a natural mutation in less than 1 percent of Caucasians that results in a lack of CCR5 receptors on any of their cells.

"We also found that these people are naturally resistant to HIV," said Bauer. "So, more than 10 years ago, we began our work creating a gene that would knock down expression of CCR5 and other key receptors and interfere with other routes of HIV infection."

For IPS-based anti-HIV gene therapy to become reality, UC Davis researchers must first conduct safety and efficacy trials. Researchers have created a mouse model that replicates a normally functioning human immune system.

"We can now move forward and test the safety of the viral vectors, as well as the ability of anti-HIV genes to inhibit HIV infection," noted Anderson. "The humanized mouse model is an important step toward bringing this possible cure to patients."

Bauer and Anderson are hoping to demonstrate in their mouse model that HIV-infection cannot occur following their gene therapy treatment, providing the needed confidence in safety before embarking on clinical trials. This work and studies on the clinical use of IPS cells, Bauer predicts, will lead to a cure for AIDS.

"A real cure will come when we can replace all the hematopoietic stem cells with HIV resistant stem cells. What is so exciting is that we're clearly on the path of doing just that," said Bauer.

Source

[freewillie99]

Cool article from a few months ago about researchers at Cal Davis (one of which is quoted in the article above, Gerhard Bauer) demonstrating the safety of taking adult blood-forming cells found in bone marrow (known as hematopoietic stem cells) from a person who needs treatment, genetically modifying the cells  and then re-inserting the cells back into the same person.  Very cool.

http://www.ascrnetwork.org/component/content/article/40-may-2008/131-uc-davis-stem-cell-researchers-demonstrate-safety-of-gene-therapy-using-adult-stem-cells.html

UC DAVIS STEM CELL RESEARCHERS DEMONSTRATE SAFETY OF GENE THERAPY USING ADULT STEM CELLS
         
May 6, 2008

(SACRAMENTO, Calif.) — A new study by UC Davis researchers provides evidence that methods using human bone marrow-derived stem cells to deliver gene therapy to cure diseases of the blood, bone marrow and certain types of cancer do not cause the development of tumors or leukemia. The study was published online in the May 6, 2008, issue of Molecular Therapy.

"The results of our decade-long study of adult human stem cell transplantation shows that there is little risk of adverse events caused by gene transfer, and that adult human stem cells do not pose a cancer risk when implanted into different organs," said Jan Nolta, senior author of the study and director of the UC Davis Stem Cell Program.


Nolta and her colleagues tested the safety of gene transfer into bone marrow stem cells from human donors in more than 600 mice. None of the transplanted mice developed leukemia or solid tumors caused by the gene therapy treatment, during the evaluation period of up to 18 months.

"These data are critical for advancing stem cell research leading toward therapies," Nolta said. "We've shown that adult stem cells follow natural cues to reach target locations, they function normally when they get there and do not exhibit the unchecked cell growth that is the hallmark of cancer."

Gene therapy trials using human bone marrow cells began in the early 1990s and have since included roughly 1,000 patients worldwide. In 2000, a leukemia-like condition emerged in three participants in a clinical trial in France, halting the trial and calling into question the safety of the method. Researchers suspected that the gene transferred in this trial gave the transplanted cells an enhanced growth capacity that led to the cancers.

"After those studies in France, the gene therapy community felt that further biosafety testing was warranted," explained Gerhard Bauer, lead author of the study and an assistant professor of hematology and oncology. "Due to the significantly large number of study animals, our investigation further illuminates the safety of gene therapy using hematopoietic stem cells. It allows us to rest easier with the knowledge that if we insert corrective genes into human bone marrow stem cells and administer those cells to human patients, we are providing a relatively safe therapy."

Today, gene therapy using the adult blood-forming cells found in bone marrow (known as hematopoietic stem cells) is normally done in an autologous transplant setting. The therapy involves taking hematopoietic stem cells from a person who needs treatment, genetically modifying the cells — perhaps by adding a missing gene — and then re-inserting the cells back into the same person. This treatment eliminates the complications of graft-versus-host disease or host rejection that can occur in allogeneic transplants (therapy where the cell donor is different from the recipient).

In the current study, 630 immunodeficient mice received mesenchymal stem cells from one human bone marrow donor and hematopoietic stem cells from another. Mesenchymal stem cells are a type of cell found in bone marrow that support the function of hematopoietic stem cells, and can give rise to bone, cartilage, fat, and muscle. Genes were inserted into the hematopoietic stem cells using one of two viral vectors — either a retrovirus or a lentivirus — before they were transplanted into the mice, along with genetically modified mesenchymal stem cells.

Of the mice used in the long-term study, four developed human leukemia. None of those mice, however, were found to have vector DNA present in the malignant cells.

"This is evidence of a natural tendency for human bone marrow stem cells to develop leukemia in long-term studies, not that the leukemia was caused by the genetic modification," Bauer explained. "It's a good statistical control for our method."

Bauer noted that while the current study results are important for use with adult stem cells, they are not applicable to human embryonic stem cells, which have completely different properties.

"Our experiments did not involve human embryonic stem cells, so we have a lot of stringent work to do to ensure that those types of stem cells can be used safely for human clinical trials," said Bauer. "It certainly is possible, and we are working hard to establish safe and effective human embryonic stem cell-based cures for patients as well."

Nolta and Bauer have worked on eighteen cell and gene therapy clinical therapy trials during their 12 years as colleagues, including stem cell gene therapy trials for adenosine deaminase deficiency, also known as the "Bubble Boy Disease," and stem cell gene therapy for HIV, with colleagues from Children's Hospital Los Angeles, who are also co-authors on the current report.

Bauer is the director of UC Davis' Good Manufacturing Practice (GMP) laboratory in Sacramento. Upon its completion, UC Davis will be one of the few universities with a large GMP facility where scientists will work in an ultra-clean environment to derive cellular products that, after certification and extensive testing, will be used to treat patients. The California Institute for Regenerative Medicine (CIRM) has recommended funding for this new facility to help bring a wide range of stem cell therapy cures to patients throughout California.

According to Nolta, the results of the current study will allow UC Davis to move forward with increased certainty as it prepares for clinical trials.

"We are ready to further develop and test this safe approach to creating effective therapies, and are also using the same model to test the safety of embryonic stem cell-based therapies to fulfill the promise of regenerative medicine." she said.

This work was supported by the National Institutes of Health through the National Heart, Lung and Blood Institute/National Institutes of Diabetes and Digestive and Kidney Diseases; The John Connell Gene Therapy Foundation; a Career Development Award from the Children's Hospital of Los Angeles Research Institute, and UC Davis Stem Cell Program start-up funding.

About UC Davis Stem Cell Research
UC Davis has more than 125 basic, translational, and clinical faculty members working together on a variety of adult and embryonic stem cell investigations in both Davis and Sacramento. The university is currently renovating a 100,000 square foot stem cell research facility on its campus in Sacramento, where researchers will have access to state-of-the-art laboratories and cell manufacturing and testing rooms. That project, along with its Translational Human Embryonic Stem Cell Shared Research Facility in Davis complements the university's Clinical and Translational Science Center, which is supported by the National Institutes of Health (NIH). In 2005, the NIH awarded $6 million to fund a Center of Excellence in Translational Human Stem Cell Research on the Davis campus. One of only two such centers in the nation, it is focused on exploring stem and progenitor cell therapies for the treatment of childhood diseases. The California Institute for Regenerative Medicine (CIRM) has awarded more than $14 million to researchers at UC Davis, to develop stem cell cures. The programs are designed to expedite the translation and integration of scientific research into discoveries and treatments that benefit society.

[freewillie99]

He's baaaack...

The New England Journal of Medicine published an article about the famed "German Patient" yesterday.  Because I don't subscribe to the NEJM, here's an overview off CNN:

http://www.cnn.com/2009/HEALTH/02/11/health.hiv.stemcell/index.html

Man appears free of HIV after stem cell transplant

STORY HIGHLIGHTS
American patient in Germany without signs of HIV and not on antiretroviral medicine
Man underwent stem cell transplant to treat his leukemia, not HIV
Procedure isn't feasible for majority of HIV patients, because transplant is dangerous

By Jacquelyne Froeber
 
A 42-year-old HIV patient with leukemia appears to have no detectable HIV in his blood and no symptoms after a stem cell transplant from a donor carrying a gene mutation that confers natural resistance to the virus that causes AIDS, according to a report published Wednesday in the New England Journal of Medicine.

The patient underwent a stem cell transplant and since, has not tested positive for HIV in his blood.

"The patient is fine," said Dr. Gero Hutter of Charite Universitatsmedizin Berlin in Germany. "Today, two years after his transplantation, he is still without any signs of HIV disease and without antiretroviral medication."

The case was first reported in November, and the new report is the first official publication of the case in a medical journal. Hutter and a team of medical professionals performed the stem cell transplant on the patient, an American living in Germany, to treat the man's leukemia, not the HIV itself.

However, the team deliberately chose a compatible donor who has a naturally occurring gene mutation that confers resistance to HIV. The mutation cripples a receptor known as CCR5, which is normally found on the surface of T cells, the type of immune system cells attacked by HIV.

The mutation is known as CCR5 delta32 and is found in 1 percent to 3 percent of white populations of European descent.

HIV uses the CCR5 as a co-receptor (in addition to CD4 receptors) to latch on to and ultimately destroy immune system cells. Since the virus can't gain a foothold on cells that lack CCR5, people who have the mutation have natural protection. (There are other, less common HIV strains that use different co-receptors.)

People who inherit one copy of CCR5 delta32 take longer to get sick or develop AIDS if infected with HIV. People with two copies (one from each parent) may not become infected at all. The stem cell donor had two copies.

While promising, the treatment is unlikely to help the vast majority of people infected with HIV, said Dr. Jay Levy, a professor at the University of California San Francisco, who wrote an editorial accompanying the study. A stem cell transplant is too extreme and too dangerous to be used as a routine treatment, he said.

"About a third of the people die [during such transplants], so it's just too much of a risk," Levy said. To perform a stem cell transplant, doctors intentionally destroy a patient's immune system, leaving the patient vulnerable to infection, and then reintroduce a donor's stem cells (which are from either bone marrow or blood) in an effort to establish a new, healthy immune system.

Levy also said it's unlikely that the transplant truly cured the patient in this study. HIV can infect many other types of cells and may be hiding out in the patient's body to resurface at a later time, he said.

"This type of virus can infect macrophages (another type of white blood cell that expresses CCR5) and other cells, like the brain cells, and it could live a lifetime. But if it can't spread, you never see it-- but it's there and it could do some damage," he said. "It's not the kind of approach that you could say, 'I've cured you.' I've eliminated the virus from your body."

Before undergoing the transplant, the patient was also found to be infected with low levels of a type of HIV known as X4, which does not use the CCR5 receptor to infect cells. So it would seem that this virus would still be able to grow and damage immune cells in his body. However, following the transplant, signs of leukemia and HIV were absent.

"There is no really conclusive explanation why we didn't observe any rebound of HIV," Hutter said. "This finding is very surprising."

Hutter noted that one year ago, the patient had a relapse of leukemia and a second transplant from the same donor. The patient experienced complications from the procedure, including temporary liver problems and kidney failure, but they were not unusual and may occur in HIV-negative patients, he said.

Researchers including Hutter agree that the technique should not be used to treat HIV alone. "Some people may say, 'I want to do it,'" said Levy. A more logical -- and potentially safer -- approach would be to develop some type of CCR5-disabling gene therapy or treatment that could be directly injected into the body, said Levy.

Less invasive options to alter CCR5 could be on the horizon within the next five years, said Levy. "It's definitely the wave of the future," he said. "As we continue to follow this one patient, we will learn a lot."

One drug that's currently on the market that blocks CCR5 is called maraviroc (Selzentry). It was first approved in 2007 and is used in combination with other antiretroviral drugs.

In 2007, an estimated 2 million people died from AIDS, and 2.7 million people contracted HIV. More than 15 million women are infected worldwide. HIV/AIDS can be transmitted through sexual intercourse, sharing needles, pregnancy, breast-feeding, and/or blood transfusions with an infected person. Health.com:What should I do if the condom breaks?

"For HIV patients, this report is an important flicker of hope that antiretroviral therapy like HAART [highly active antiretroviral therapy] is not the endpoint of medical research," Hutter said.   

[tommy246]

Two days ago there was a full page talking about the well known german discovery that treated the lukemia patient 3 years ago with a bone marrow transplant and saying he is cured of aids.
They hope by making stem cells in the lab from people with natural defence to hiv(3%) that in five years time we could start curing people.It also said that it would probably be immpossible to treat the whole world and that it would probably be given to people that are drug resistant.
I dont know how much to read into this news but it was in the paper so just thought i would post it.

[Matts]

Daily Express: http://www.express.co.uk/printer/view/97157/

Thank You,Interesting news, not much published about this so far, only this one in german: "New attempts at the Charité" Link

It seems they want to repeat the surgery more often in the future, also with patients without leukemia.

[Ann]

Tommy, you should read this thread on this subject:

   
German transplant operation eradicates HIV

Ann

[freewillie99]

This continues to be one of the most exciting fronts in the battle for a cure.  Hopefully at some point someone will figure out a more benign way to achieve ablation (clearing) of existing bone marrow pre-transplant.  Heavy duty chemo and radiation treatments aren't exactly walks in the park.

edit:

Here's an example of what researchers are working on to more benignly clear bone marrow / hematopoietic stem cells:

"COPYRIGHT 2007 Science Service, Inc.

A bone marrow transplant preceded by destruction of one's own bone marrow with radiation or chemotherapy is a bleak prospect for a leukemia patient. Although the procedure can be lifesaving, it carries toxicity risks and weakens the patient. That's why people with autoimmune diseases rarely get a marrow transplant--even though it's potentially curative.

Scientists have now devised a synthetic antibody called ACK2 that targets a protein displayed on the surface of marrow cells and destroys them without radiation or chemo. These marrow cells, also called hematopoietic stem cells, can develop into various immune cells. In autoimmune diseases, some of them run amok and orchestrate tissue damage.

When researchers gave ACK2 to mice, it wiped out roughly 98 percent of the animals' marrow cells with few side effects. After the ACK2 had cleared from the animals' blood, the researchers gave them healthy donor marrow cells, which developed into a nondefective immune system.

Immunologist Agnieszka Czechowiez of Stanford University School of Medicine and her colleagues found that treating mice with ACK2 left prominent niches in bone marrow where replacement cells could grow. She doesn't envision ACK2 as a treatment for leukemia patients since it doesn't specifically target cancer cells. But it might benefit people with noncancerous immune disorders such as type 1 diabetes, multiple sclerosis, or sickle cell disease, Czechowicz says. --N.S.

COPYRIGHT 2007 Science Service, Inc.

[Ann]

 Heavy duty chemo and radiation treatments aren't exactly walks in the park.

Absolutely. That's why I wanted Tommy to read that other thread - these aspects of this potential cure are discussed there.

Ann

[freewillie99]

these aspects of this potential cure are discussed there.

Ann

It's a very informative thread, no doubt.  The guy who started it seems to be on top of things

[Inchlingblue]

One thing I liked about this piece in the Sunday Express is that they went into a little more detail about the condition of the patient now. Everything else I read reported that he is free of virus etc but I kept wondering if he is OK otherwise, in terms of his general health and here they say he is:

“We are convinced this treatment works. The patient we treated three years ago is perfectly healthy and we are sure the HIV virus has gone and will not come back. But we will want to carry out trials on other patients.
“Our patient is doing very well and is completely clear of the virus and living a normal life.”


One thing I don't get about the article, because it sounds contradictory to me is that they say:

But experts hope that it will be possible to take the bone marrow from a few donors and grow an inexhaustible supply of stem cells in the laboratory.

And then they say:

“It won’t be for everyone because of the limitation on the number of donors in the population who have this natural resistance to HIV.

If you can grow an "inexhaustible supply" then why should there be limitations as far as number of donors?

 

[Matts]

You are right, the Sunday Express is a bit unclear.
“It won’t be for everyone because of the limitation on the number of donors in the population who have this natural resistance to HIV." I think this is the opinion of Professor John Goldman of London’s Hammersmith Hospital, but the newspaper doesn't tell who are the experts who want to "grow  an inexhaustible supply of stem cells in the laboratory".hmm

But the american patient is fine and he is working again; and Dr. Huetter's surgery possibly won't be a single case, as told so far. Good news

"AIDS treatment
New attempts at the Charité"  BZ 18.April 2009 (autotranslated)


The first cured AIDS patient was a sensation. Now terminate the Charité doctors to new surgeries.

This man wants to bring them. He ha salready healed AIDS. Now he wants to do it again. In series.
Eckhard Thiel, the Director of the medical clinic with Hematology and Oncology, the Charité.
 
He and his colleagues treated a 42-years old in November. He was almost dead, when he came to Benjamin Franklin Hospital. And became the first cured AIDS patient. "We had with the healing a greater success." We must now strengthen ", says Thiel and announces new operations - new healing attempts.

It is to expect that more patients be treated by our method. Still 2009. In Heidelberg, Freiburg, also in Berlin. It is possible, that the HI virus starves to death in the cells in these patients that they are then cured. The plan is to set. ""

33 Million people worldwide suffer  the HIV virus. A disease, get more people every day in Berlin. The Prof. Dr. Dr. Mut of the Charité promises: "A clinic such as my or the Virchow hospital could to make a operation safe every week."

Using a mood of nature as the healing method 

Ten years contributed Thiels first patient the virus in. An American. He suffered leukemia. The Charité doctors made a bone marrow transplant against cancer in the blood and cured equal with AIDS. Over two years is now without proven HI virus in his blood. He works again. Was already in November again in his advertising agency. The doctors could watch as life returned into him.

The miracle method of Thiels Charité pros. It uses a mood of nature. The physician search for a donor, who is immune thanks to a Genmutation against HIV. This Blockierer DNA occurs only once under 100 people when Europeans. It ensures that the dangerous virus can't go into human cells.

Thiel: "after successful surgery many hundred requests arrived from all overthe world, people from all countries, South America, India, Russia is reported who wanted to make a bone marrow transplant." The questions don't stop

 Meeting of top physicians in Berlin
Now he makes new hope. More operations for more patients. On the great breakthrough. A top meeting of international stem cell experts in Berlin takes place on Monday. Objective: not more only leukemia suffering patients, but also other HIV patients, should new therapy heal, if the drugs no longer help. In Germany there are still ethical concerns.

in America run already attempts to Thiel. "Ifour method proves,comes the next step", he says.the permission that such operations also with us without leukemia can be made may take up to one year. We are discussing how tests can be. ""

[hahaha]

"AIDS treatment
New attempts at the Charité"  BZ 18.April 2009 (autotranslated)

The first cured AIDS patient was a sensation. Now terminate the Charité doctors to new surgeries.

This man wants to bring them. He ha salready healed AIDS. Now he wants to do it again. In series.
Eckhard Thiel, the Director of the medical clinic with Hematology and Oncology, the Charité.
 

I am wondering, since his announcement of this patient status, is he still the "one and only one" doctor who would perform this experiment again?    I ask this question is because I personally would like to give a try as well.  But so far as I know from the news, it seems no one is repeating the same experiment.   Is it because of the law? or because the pairing is difficult to find?  Or simply because "some Dr. has done the experiment, so I won't do it?" 

I beliieve a method to be proof effecive needs more than one case for confirmation.   But it seems hard to find any further information on "other" Doctors.  Does anyone have a clue about it?

[Ann]

But so far as I know from the news, it seems no one is repeating the same experiment.   Is it because of the law? or because the pairing is difficult to find?  Or simply because "some Dr. has done the experiment, so I won't do it?" 

As far as I am aware, it's probably because of all the obstacles in the way. It's not a simple thing to do at all and the health-risks are great. Did you read the other thread I linked to? It's discussed there.

Ann

[Inchlingblue]

I am wondering, since his announcement of this patient status, is he still the "one and only one" doctor who would perform this experiment again?    I ask this question is because I personally would like to give a try as well.  But so far as I know from the news, it seems no one is repeating the same experiment.   Is it because of the law? or because the pairing is difficult to find?  Or simply because "some Dr. has done the experiment, so I won't do it?" 

I beliieve a method to be proof effecive needs more than one case for confirmation.   But it seems hard to find any further information on "other" Doctors.  Does anyone have a clue about it?

Based on the article that Matts reprinted above it sounds like they are gearing up to try this on other patients with just HIV and not leukemia in about a year (after they secure the proper permissions to proceed). You can maybe contact them by email or something. The automatic translation is awkward but that's how I read it:

Meeting of top physicians in Berlin
Now he makes new hope. More operations for more patients. On the great breakthrough. A top meeting of international stem cell experts in Berlin takes place on Monday. Objective: not more only leukemia suffering patients, but also other HIV patients, should new therapy heal, if the drugs no longer help. In Germany there are still ethical concerns.

in America run already attempts to Thiel. "If our method proves,comes the next step", he says.the permission that such operations also with us without leukemia can be made may take up to one year. We are discussing how tests can be. ""


As difficult as it must be on one's body to destroy the bone marrow (the chances of survival are 30%), I agree with you that it's very tempting. This American patient in Berlin who had it was, I suppose, lucky to survive at all, let alone emerge from it cured of both his HIV and his leukemia, talk about hitting a double jackpot@!  You have to consider that he was already a very sick man when he underwent this procedure, close to dying according to some of the accounts I've read.

You would think that if the procedure is done on someone who is overall in much better health than this guy was when he had it done, their chances would be better. One prominent doctor was quoted as saying he'd rather take HAART for the rest of his life than have this done, but then again, he's HIV- and can't speak from direct experience having HIV.

I think the important "take home" message with all of this is that the success of the Berlin patient has served as proof of concept that this is do-able and achievable. It should now be fully explored as a real option for ridding the body of HIV.  Once that ball starts rolling, it is bound to be perfected and fine-tuned. There are ways to do this without completely destroying bone marrow and there are also ways, using gene therapy, to implement the Delta 32 mutation without the use of donors. The important thing is that this continues to be explored and researched and experimented on until a safe and effective version of this procedure is found.

I do agree with you, though, I also would be very tempted to be a guinea pig for this.

[freewillie99]

As difficult as it must be on one's body to destroy the bone marrow (the chances of survival are 30%)

You need to amend this percentage.  70% of bone marrow transplant recipients don't die.  This is wildly inaccurate. 

[Matts]

This continues to be one of the most exciting fronts in the battle for a cure.  Hopefully at some point someone will figure out a more benign way to achieve ablation (clearing) of existing bone marrow pre-transplant.  Heavy duty chemo and radiation treatments aren't exactly walks in the park.

This so true. If this problem could be solved, I am sure we would have a solution for widespread use.

"Philip Gregory (Sangomo Biosciences, Zinc Finger Nucleases) says that in the long term, it might be even more effective to extract and modify a different type of cell, called CD34 cells. Since they are stem cells, they can become every type of white blood cell, so this would eventually make the patient's entire immune system resistant to HIV, which would be closer to the German leukaemia patient's experience.

However, Gregory points out that engineering stem cells, rather than CD4 cells, raises the dilemma of whether to make room for the altered stem cells by destroying the patient's existing bone marrow cells, which is what happened in the patient in Germany."
Source: Newscientist Link

"Building an HIV-Proof Immune System: New HIV Gene Therapy Trials" Natap 2007: Link

Unfortunately it seems to be quite useless  to modify only CD4 or Cd34 without ablation and  reinjecting them into the body  (Johnson& Johnson OZ1, current Sangamo ZNF trial, VIRxSYS). But if there would be a safe and easy way of (partial) myeoablation in the future, (maybe antibody  ACK2, as Freewillie 99 posted), then a real success could be possible.

BTW, I found the last comment of the Newscientist article interesting. It was written by Christopher Bremner, Main Shareholder of Benitec Australia. He invested some Mio.$ and stated: "  Dr Rossi and Benitec , the discoverer of RNAi have treated 5 Aids Lymphoma and Lukaemia patients with autologous bone marrow transplantantion with T cell genetically modified to be immune to AIDS , one year on the patients who were terminal prior to treatment are all cancer and AIDS free. HIV Viral titers are zero."

Ok, I wait for the next Press Release, if this is really true. This City of Hope Project is promising, because they use  three different ways to Block HIV, not only CCR5.

[Inchlingblue]

You need to amend this percentage.  70% of bone marrow transplant recipients don't die.  This is wildly inaccurate. 

Yes, I meant to say the other way around, the treatment kills roughly 30%. Thanks for pointing it out.

[Inchlingblue]

I came across this piece about the procedure done on the Berlin patient which I wanted to share because, at least from all the articles on the subject that I've seen, this gives one of the most complete rundowns of what was actually done to the patient.

For example, I didn't know that he already had one copy of the CCR5 mutation as part of his own DNA and that he actually received two separate bone marrow transplants (from the same donor) because his leukemia had relapsed 11 months after the first transplant.

LINK:

http://www.nhs.uk/news/2009/02February/Pages/HIVGeneTreatment.aspx

[Ann]

Tommy, I edited your original post in this thread simply to change the thread title to one that more accurately describes the thread's topic. The title is the ONLY thing I altered in your post. Hope you don't mind.

I'm also tempted to merge this thread with the original. Thoughts?


Ann

[freewillie99]

I'm also tempted to merge this thread with the original. Thoughts?

You're talking about the German Patient thread?  Probably not a bad idea as this thread is essentially a continuation of that story.

[Inchlingblue]

BTW, I found the last comment of the Newscientist article interesting. It was written by Christopher Bremner, Main Shareholder of Benitec Australia. He invested some Mio.$ and stated: "  Dr Rossi and Benitec , the discoverer of RNAi have treated 5 Aids Lymphoma and Lukaemia patients with autologous bone marrow transplantantion with T cell genetically modified to be immune to AIDS , one year on the patients who were terminal prior to treatment are all cancer and AIDS free. HIV Viral titers are zero."

Matts: Maybe I missed it but I can't find a link to the Newscientist article that you mention above, do you have a link? Thanks!

[freewillie99]

Matts: Maybe I missed it but I can't find a link to the Newscientist article that you mention above, do you have a link? Thanks!

Here ya go:

http://www.newscientist.com/article/mg20126964.400-gene-therapy-promises-oneshot-treatment-for-hiv.html

[Inchlingblue]

That was an excellent article, thanks Freewillie

EDIT:

Even though I loved the article I just realized it's not the same one that Matts had mentioned, which he said was written by Christopher Bremner and this one was written by Andy Coghlan.

[veritas]

Free,

As you know, I have been following anti-ps closely and I believe that anti-ps is a pathway to "the holy grail". BUT, let me tell you I don't care where the cure comes from as long as it comes. This research looks promising ( I do admit that I think I would shy away from a bone marrow transplant) . If they can develop the therapy minus the transplant ,I'm in.

Nice article.

v

[freewillie99]

Even though I loved the article I just realized it's not the same one that Matts had mentioned, which he said was written by Christopher Bremner and this one was written by Andy Coghlan.

It actually is the same article.  Matts was referring to a comment (it should be right at the end) allegedly written by Dr. Christopher Bremner, the major stakeholder in Benitec.  Given the poor spelling and grammar in the comment, I seriously doubt it was him.

[freewillie99]

Free,

As you know, I have been following anti-ps closely and I believe that anti-ps is a pathway to "the holy grail". BUT, let me tell you I don't care where the cure comes from as long as it comes. This research looks promising ( I do admit that I think I would shy away from a bone marrow transplant) . If they can develop the therapy minus the transplant ,I'm in.

Nice article.

v

It's really not the bone marrow transplant that's the issue per se, it's the heavy duty chemo and radiation that's required in order to achieve ablation (clearing) of the existing bone marrow prior to the actual transplantation.  If and when they figure out a more benign method to do this that doesn't have such a high mortality rate and negative effects attached to it, it's going to be interesting to see what happens with this type of therapy.

[bocker3]

It's really not the bone marrow transplant that's the issue per se, it's the heavy duty chemo and radiation that's required in order to achieve ablation (clearing) of the existing bone marrow prior to the actual transplantation.  If and when they figure out a more benign method to do this that doesn't have such a high mortality rate and negative effects attached to it, it's going to be interesting to see what happens with this type of therapy.

It's also the failure of the transplant to "take", leaving you with no marrow and therefore no way to make blood cells (immune or otherwise).

Even if all of these "negative effects" are overcome -- where will we be able to get millions of marrow donors??  I've seen many marrow extractions -- it is an exceedingly unpleasant endeavor for the donor.

M

[freewillie99]

It's also the failure of the transplant to "take", leaving you with no marrow and therefore no way to make blood cells (immune or otherwise).

Even if all of these "negative effects" are overcome -- where will we be able to get millions of marrow donors??  I've seen many marrow extractions -- it is an exceedingly unpleasant endeavor for the donor.

M

Bocker:

Interesting.  How often does the transplant not "take", and if it doesn't, does the patient simply die?  I was under the impression that bone marrow transplants, as unpleasant and serious a procedure as they might be, were fairly common with some type cancer patients.

As for the "millions of marrow donors", absolutely.  Given the minute percentage of people with the mutation required for HIV immunity, this of course is completely impractical.  However, it seems I've read about the ability to modify and manipulate hematopoietic stems cells so that they possess this immunity.  Assuming this is possible, in your opinion wouldn't this overcome the need to find a compatible donor with HIV shunning mutations?

Thanks.  Appreciate the insight from someone in the medical field.

[freewillie99]

Here's a cool YouTube that shows how Zinc Finger Nucleases (ZFN) can be used to modify the genome.

http://www.youtube.com/watch?v=1Ah8lZ4sZFw

[bocker3]

Bocker:

Interesting.  How often does the transplant not "take", and if it doesn't, does the patient simply die?  I was under the impression that bone marrow transplants, as unpleasant and serious a procedure as they might be, were fairly common with some type cancer patients.

As for the "millions of marrow donors", absolutely.  Given the minute percentage of people with the mutation required for HIV immunity, this of course is completely impractical.  However, it seems I've read about the ability to modify and manipulate hematopoietic stems cells so that they possess this immunity.  Assuming this is possible, in your opinion wouldn't this overcome the need to find a compatible donor with HIV shunning mutations?

Thanks.  Appreciate the insight from someone in the medical field.

I'm not sure how often a donation doesn't take off hand, but even if rare, it's probably a risk that is too great for most.  Remember, while you may be eliminating the "host's" immune system (for the most part), and therefore minimizing the host "rejecting" the graft -- you are putting someone else's "cellular immune system" into the host and you run the risk of this immune system rejecting the host.  The whole idea of doing this type of BM transplant for anyone who is not in a "last resort" type of setting is troubling.
Even if they are able to find a way to "manipulate" stem cells (this could negate the need for millions of donors, although the stem cells do have to come from somewhere), the prospect of wiping out all of someone's marrow (and all that this ultimately means....) when it is not truly and life or death matter is the crux of the problem here.  I, for one, prefer my odds of living on drugs vs. taking that sort of risk with my life.

Now -- before anyone goes crazy on me -- I'm not saying this shouldn't be explored, but I think there will be great difficulty in finding "volunteers" for further "tests".

Mike

[trellium]

Interesting.  How often does the transplant not "take", and if it doesn't, does the patient simply die?  I was under the impression that bone marrow transplants, as unpleasant and serious a procedure as they might be, were fairly common with some type cancer patients.

Check out Graft-versus-host disease (GVHD)
http://www.nlm.nih.gov/medlineplus/ency/article/001309.htm

"Acute GVHD starts within the first 3 months after transplant. Chronic GVHD starts more than 3 months after transplant, and can last for 3 years or longer.

Rates of GVHD vary from between 30-40% among related donors and recipients to 60-80% between unrelated donors and recipients. The greater the mismatch between donor and recipient, the greater the risk of GVHD. After a bone marrow transplant, the recipient usually takes drugs that suppress the immune system, which helps reduce the chances (or severity) of GVHD."

[freewillie99]

Obviously getting a bone marrow transplant using current standards is brutal.  Let's hope that a more benign method of ablation is devised.