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Author Topic: Bone marrow transplant cures hiv infection  (Read 23625 times)

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Offline SASA39

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Re: German transplant operation eradicates HIV
« Reply #50 on: December 01, 2008, 05:38:02 AM »
Thank you David
Oct.     `06.  CD4=58  ?    %       VL not perform. ?!?
25.Dec.`06.         203       14        VL= 0
29.May.`07.    broken device        VL=1363
20.June`07     broken device        VL=0
25.Dec `07  CD4=582                  VL=70
14.May `08  CD4=448
29.July `08                                  VL=0
26.Nov `08  CD4=674                    VL=179
16.Mar `09  CD4=554                    VL=0
19.Jan`10 CD4=715               
03.Mar`10                                    VL=0
24.Aug`10 CD4=524                     VL=0
04.Dec`10 CD4=626                     VL=0
15.Sep`11                                   VL=93
17.Nov`11                                   VL=0
05/26 .Jul`12 CD4=713                 VL=0
28.Nov`12 CD4=916                     VL=0
09.May`13                                 VL=0

Offline John2038

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Re: German transplant operation eradicates HIV
« Reply #51 on: December 01, 2008, 06:11:01 AM »
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.

Offline freewillie99

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Re: German transplant operation eradicates HIV
« Reply #52 on: December 01, 2008, 10:36:23 AM »
Thanks for the add, David.  Very interesting.
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Offline freewillie99

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Re: German transplant operation eradicates HIV
« Reply #53 on: December 04, 2008, 03:00:50 PM »
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   
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Offline NYCguy

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Re: German transplant operation eradicates HIV
« Reply #54 on: December 04, 2008, 03:43:51 PM »
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.
11/9/06 = #$%^&!
sometime early Dec 2006:
CD4 530 20%/VL >250,000 (&*$$%!!)
started Reyataz300mg/Norvir/Truvada 12-27-06.
1/30/07 CD4 540 30%/VL <400
4/07 CD4 600+ 33%/VL <50
6/9/07 CD4 720 37%/VL <50
10/15/07 CD4 891 (!) %? VL <50
1/2010 CD4 599 (37%) VL<50 (drop due to acute HCV)
9/2010 - looks like HCV is gone for good! And I'm finally drinking again, thank GOD
2013 - considering a switch to Stribild. but I love my Kidneys (but I hate farting all the time!)...
June 2013 - switched to Stribild.  so far so good...

Offline freewillie99

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Re: German transplant operation eradicates HIV
« Reply #55 on: December 04, 2008, 03:49:41 PM »
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
« Last Edit: December 04, 2008, 04:14:58 PM by freewillie99 »
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Offline NYCguy

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Re: German transplant operation eradicates HIV
« Reply #56 on: December 04, 2008, 04:35:10 PM »
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.
11/9/06 = #$%^&!
sometime early Dec 2006:
CD4 530 20%/VL >250,000 (&*$$%!!)
started Reyataz300mg/Norvir/Truvada 12-27-06.
1/30/07 CD4 540 30%/VL <400
4/07 CD4 600+ 33%/VL <50
6/9/07 CD4 720 37%/VL <50
10/15/07 CD4 891 (!) %? VL <50
1/2010 CD4 599 (37%) VL<50 (drop due to acute HCV)
9/2010 - looks like HCV is gone for good! And I'm finally drinking again, thank GOD
2013 - considering a switch to Stribild. but I love my Kidneys (but I hate farting all the time!)...
June 2013 - switched to Stribild.  so far so good...

Offline leit

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Re: German transplant operation eradicates HIV
« Reply #57 on: December 04, 2008, 08:17:18 PM »
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.
« Last Edit: December 05, 2008, 11:10:12 AM by leit »

Offline John2038

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Re: German transplant operation eradicates HIV
« Reply #58 on: December 06, 2008, 05:07:56 AM »
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

Offline freewillie99

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Re: German transplant operation eradicates HIV
« Reply #59 on: December 08, 2008, 01:17:06 PM »
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.
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Offline freewillie99

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Re: German transplant operation eradicates HIV
« Reply #60 on: February 12, 2009, 12:05:20 PM »
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.   
« Last Edit: February 12, 2009, 12:08:09 PM by freewillie99 »
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Offline tommy246

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Bone marrow transplant cures hiv infection
« Reply #61 on: April 28, 2009, 02:44:49 AM »
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.
« Last Edit: May 01, 2009, 08:15:46 AM by Ann »
jan 06 neg
dec 08 pos cd4 505 ,16%, 1,500vl
april 09 cd4 635 ,16%,60,000
july 09 ,cd4 545,17%,80,000
aug 09,hosptal 18days pneumonia cd190,225,000,15%
1 week later cd4 415 20%
nov 09 cd4 591 ,vl 59,000,14%,started atripla
dec 09  cd4 787, vl 266, 16%
march 2010  cd4 720 vl non detectable -20  20%
june 2010  cd4  680, 21%, ND

Offline Matts

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Re: English sunday express newspaper
« Reply #62 on: April 28, 2009, 05:25:46 AM »
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.
« Last Edit: April 28, 2009, 03:43:09 PM by Matts »
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Offline Ann

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Re: English sunday express newspaper
« Reply #63 on: April 28, 2009, 07:51:41 AM »
Tommy, you should read this thread on this subject:

   
German transplant operation eradicates HIV


Ann
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Offline freewillie99

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Re: English sunday express newspaper
« Reply #64 on: April 28, 2009, 07:57:03 AM »
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.
« Last Edit: April 28, 2009, 08:33:09 AM by freewillie99 »
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Offline Ann

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Re: English sunday express newspaper
« Reply #65 on: April 28, 2009, 08:01:22 AM »
 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.

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Offline freewillie99

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Re: English sunday express newspaper
« Reply #66 on: April 28, 2009, 08:13:19 AM »
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 :)
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Offline Inchlingblue

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Re: English sunday express newspaper
« Reply #67 on: April 28, 2009, 02:31:09 PM »
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?

 
« Last Edit: April 28, 2009, 04:19:24 PM by Inchlingblue »

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Re: English sunday express newspaper
« Reply #68 on: April 28, 2009, 03:41:55 PM »
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. ""
« Last Edit: April 28, 2009, 03:44:24 PM by Matts »
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Offline hahaha

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Re: English sunday express newspaper
« Reply #69 on: April 29, 2009, 02:25:37 AM »

"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?
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Offline Ann

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Re: English sunday express newspaper
« Reply #70 on: April 29, 2009, 07:22:49 AM »

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
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"...health will finally be seen not as a blessing to be wished for, but as a human right to be fought for." Kofi Annan

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HIV is certainly character-building. It's made me see all of the shallow things we cling to, like ego and vanity. Of course, I'd rather have a few more T-cells and a little less character. Randy Shilts

Offline Inchlingblue

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Re: English sunday express newspaper
« Reply #71 on: April 29, 2009, 12:09:19 PM »
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.
« Last Edit: April 29, 2009, 12:23:58 PM by Inchlingblue »

Offline freewillie99

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Re: English sunday express newspaper
« Reply #72 on: April 30, 2009, 01:33:27 PM »
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. 
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Offline Matts

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Re: English sunday express newspaper
« Reply #73 on: April 30, 2009, 03:10:06 PM »
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.
« Last Edit: April 30, 2009, 03:28:05 PM by Matts »
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Offline Inchlingblue

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Re: English sunday express newspaper
« Reply #74 on: April 30, 2009, 04:11:07 PM »
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.

Offline Inchlingblue

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Re: English sunday express newspaper
« Reply #75 on: April 30, 2009, 04:35:28 PM »
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

Offline Ann

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Re: Bone marrow transplant cures hiv infection
« Reply #76 on: May 01, 2009, 08:16:55 AM »
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
« Last Edit: May 01, 2009, 08:18:36 AM by Ann »
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HIV is certainly character-building. It's made me see all of the shallow things we cling to, like ego and vanity. Of course, I'd rather have a few more T-cells and a little less character. Randy Shilts

Offline freewillie99

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Re: Bone marrow transplant cures hiv infection
« Reply #77 on: May 01, 2009, 10:42:12 AM »
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.
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Offline Inchlingblue

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Re: English sunday express newspaper
« Reply #78 on: May 01, 2009, 02:43:33 PM »
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!

Offline freewillie99

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Re: English sunday express newspaper
« Reply #79 on: May 01, 2009, 03:47:12 PM »
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
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Offline Inchlingblue

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Re: Bone marrow transplant cures hiv infection
« Reply #80 on: May 01, 2009, 05:41:19 PM »
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.
« Last Edit: May 02, 2009, 04:12:51 PM by Inchlingblue »

Offline veritas

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Re: Bone marrow transplant cures hiv infection
« Reply #81 on: May 02, 2009, 03:42:11 PM »

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

Offline freewillie99

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Re: Bone marrow transplant cures hiv infection
« Reply #82 on: May 02, 2009, 08:30:52 PM »

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.
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Offline freewillie99

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Re: Bone marrow transplant cures hiv infection
« Reply #83 on: May 02, 2009, 08:37:57 PM »
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.
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Offline bocker3

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Re: Bone marrow transplant cures hiv infection
« Reply #84 on: May 04, 2009, 09:05:38 PM »
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.

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Offline freewillie99

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Re: Bone marrow transplant cures hiv infection
« Reply #85 on: May 05, 2009, 09:12:30 AM »
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.
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Offline freewillie99

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Re: Bone marrow transplant cures hiv infection
« Reply #86 on: May 05, 2009, 10:30:42 AM »
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
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Offline bocker3

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Re: Bone marrow transplant cures hiv infection
« Reply #87 on: May 05, 2009, 05:26:39 PM »
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
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Offline trellium

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Re: Bone marrow transplant cures hiv infection
« Reply #88 on: May 06, 2009, 11:44:00 AM »

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."

Offline freewillie99

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Re: Bone marrow transplant cures hiv infection
« Reply #89 on: May 08, 2009, 10:21:33 AM »
Obviously getting a bone marrow transplant using current standards is brutal.  Let's hope that a more benign method of ablation is devised.
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