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Author Topic: Poz, but in a good way?  (Read 2526 times)

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Offline Assurbanipal

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Poz, but in a good way?
« on: November 06, 2009, 09:10:33 PM »
The AP is reporting a startling successful gene therapy trial in France, that used modified HIV to cure two boys of the "Lorenzo's Oil" brain disease.  Basically the scientists used HIV to infect the boys's bone marrow stem cells with a gene that would cure the disease, wiped out their existing bone marrow and transferred in the infected stem cells. 

The scientists used HIV because of its proven ability to attach to stem cells.




WASHINGTON – French scientists mixed gene therapy and bone marrow transplants in two boys to seemingly halt a brain disease that can kill by adolescence. The surprise ingredient: They disabled the HIV virus so it couldn't cause AIDS, and then used it to carry in the healthy new gene.

...
Bone marrow transplants can halt ALD by letting new myelin-forming stem cells take root. But it's difficult to find a matching marrow donor, and the transplant itself is very risky.

So what if stem cells from the boys' own bone marrow could be genetically corrected, eliminating the ALD mutation? To do that, Aubourg's team had to overcome a technical hurdle: Gene therapy works when scientists harness deliver a healthy new gene by attaching to a virus that can harmlessly infect cells. But none of today's so-called gene therapy "vectors" could penetrate enough of the stem cells needed for an ALD treatment to work.

Unlike most viruses, HIV can penetrate stem cells, and it sticks permanently. So Aubourg's team removed the genetic parts of HIV that make it dangerous, leaving basically a scaffolding to carry the new therapeutic gene.

Then they culled stem cells from two 7-year-old boys in the early stages of ALD, and mixed in the healthy gene. The boys underwent bone marrow-destroying chemotherapy and then had their genetically corrected stem cells reinserted.


http://news.yahoo.com/s/ap/20091105/ap_on_he_me/us_med_gene_therapy

More in the context of other recent advances in gene therapy here http://www.nytimes.com/2009/11/06/health/06gene.html?ref=health
5/06 VL 1M+, CD4 22, 5% , pneumonia, thrush -- O2 support 2 months, 6/06 +Kaletra/Truvada
9/06 VL 3959 CD4 297 13.5% 12/06 VL <400 CD4 350 15.2% +Pravachol
2007 VL<400, 70, 50 CD4 408-729 16.0% -19.7%
2008 VL UD CD4 468 - 538 16.7% - 24.6% Osteoporosis 11/08 doubled Pravachol, +Calcium/D
02/09 VL 100 CD4 616 23.7% 03/09 VL 130 5/09 VL 100 CD4 540 28.4% +Actonel (osteoporosis) 7/09 VL 130
8/09  new regimen Isentress/Epzicom 9/09 VL UD CD4 621 32.7% 11/09 VL UD CD4 607 26.4% swap Isentress for Prezista/Norvir 12/09 (liver and muscle issues) VL 50
2010 VL UD CD4 573-680 26.1% - 30.9% 12/10 VL 20
2011 VL UD-20 CD4 568-673 24.7%-30.6%
2012 VL UD swap Prezista/Norvir for Reyataz drop statin CD4 768-828 26.7%-30.7%

Offline sensual1973

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Re: Poz, but in a good way?
« Reply #1 on: November 07, 2009, 04:42:47 AM »
seems like Dr. Hutters procedure,i hope those 2 events (the german patient,and the two boys) prove that curing HIV is now possible,and it should be investigated and pushed forward to be implemented very quickly.
God grant me the serenity to accept the things i can not change.

Offline georgep77

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Re: Poz, but in a good way?
« Reply #2 on: November 07, 2009, 10:06:40 AM »
This news remind me of VIRxSYS,(VRX496).. that use the HIV virus as a lentiviral vector.

            Thanks Assur for the news & link        :D
Come on Sangamo,  Geovax,  Bionor immuno, ...Make us happy !!!
+ 2008

Offline J220

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Re: Poz, but in a good way?
« Reply #3 on: November 07, 2009, 12:58:46 PM »
seems like Dr. Hutters procedure,i hope those 2 events (the german patient,and the two boys) prove that curing HIV is now possible,and it should be investigated and pushed forward to be implemented very quickly.

Well, the two boys were not hiv infected, so this cannot be used as another proof that hiv can be cured by using them as examples. But as far as the potential for gene therapy yes, it is promising.
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline Sweet_C

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Re: Poz, but in a good way?
« Reply #4 on: November 08, 2009, 12:05:48 PM »
Well, at least HIV is good for something.   :-\
Tested positive on September 11, 2008

Offline veritas

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Re: Poz, but in a good way?
« Reply #5 on: November 08, 2009, 01:16:33 PM »

J220,

I believe this is just the beginning for using HIV in studying other diseases due to the virus unigue effect upon the immune system and it's ability to protect itself from same. Now if they can only find the key to control it.

v

Offline sensual1973

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Re: Poz, but in a good way?
« Reply #6 on: November 08, 2009, 01:45:13 PM »
DESTROY it is a better word Veritas
God grant me the serenity to accept the things i can not change.

Offline Assurbanipal

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Re: Poz, but in a good way?
« Reply #7 on: November 08, 2009, 03:46:21 PM »
Well, at least HIV is good for something.   :-\

Yes.  I think the emotional context of this is at least as important for me as the research implications. In fact, I started to post it in the Living with forum, but couldn't figure out how to describe my (inchoate) reaction.  But if it becomes the basis for cures of other diseases it will certainly affect how HIV is received in the culture.

HIV has killed millions of people, many in horrible deaths.  Yet if even it could become a "vector" of hope for other diseases. . .
5/06 VL 1M+, CD4 22, 5% , pneumonia, thrush -- O2 support 2 months, 6/06 +Kaletra/Truvada
9/06 VL 3959 CD4 297 13.5% 12/06 VL <400 CD4 350 15.2% +Pravachol
2007 VL<400, 70, 50 CD4 408-729 16.0% -19.7%
2008 VL UD CD4 468 - 538 16.7% - 24.6% Osteoporosis 11/08 doubled Pravachol, +Calcium/D
02/09 VL 100 CD4 616 23.7% 03/09 VL 130 5/09 VL 100 CD4 540 28.4% +Actonel (osteoporosis) 7/09 VL 130
8/09  new regimen Isentress/Epzicom 9/09 VL UD CD4 621 32.7% 11/09 VL UD CD4 607 26.4% swap Isentress for Prezista/Norvir 12/09 (liver and muscle issues) VL 50
2010 VL UD CD4 573-680 26.1% - 30.9% 12/10 VL 20
2011 VL UD-20 CD4 568-673 24.7%-30.6%
2012 VL UD swap Prezista/Norvir for Reyataz drop statin CD4 768-828 26.7%-30.7%

Offline Inchlingblue

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Re: Poz, but in a good way?
« Reply #8 on: November 09, 2009, 09:13:49 AM »
The title of this thread is misleading because when HIV is used as a vector in gene therapy it is disabled and not infectious, so there is no way that the person can become poz this way.

Here is a nice overview explaining why HIV makes such a good vector in gene therapy:

What are lentiviral vectors?

Lentiviral vectors are a type of retrovirus that can infect both dividing and nondividing cells because their preintegration complex (virus “shell”) can get through the intact membrane of the nucleus of the target cell.  Lentiviruses can be used to provide highly effective gene therapy as lentiviruses can change the expression of their target cell's gene for up to six months.  They can be used for nondividing or terminally differentiated cells such as neurons, macrophages, hematopoietic stem cells, retinal photoreceptors, and muscle and liver cells, cell types for which previous gene therapy methods could not be used.  HIV is a very effective lentiviral vector because it has evolved to infect and express its genes in human helper T cells and other macrophages.  The only cells lentiviruses cannot gain access to are quiescent cells (in the G0 state) because this blocks the reverse transcription step (Amado and Chen, 1999).  To understand how HIV is a good vector for gene therapy, we must understand the structure of HIV and how it functions and infects its host.

Why HIV is a good vector for gene therapy?
   
The preintegration complex of the human immunodeficient virus (HIV), which allows the vector assess inside human cells, dividing or non-diving, is composed of the enzyme integrase, the product of the vpr gene (an accessory gene), and a protein encoded by the gag gene (an essential structural gene) called matrix.  This matrix protein contains a localization sequence which is recognized by the import machinery of the nucleus of a cell.  The virus is surrounded by a lipid bilayer with protruding membrane proteins.  One of these proteins, gp120, is recognized by the host helper T cell CD4 receptor protein.   Then HIV binds to a secondary receptor (CCR5 or CXCR4) and triggers a membrane fusion-mechanism with the gp41 transmembrane protein.  This allows the virus asses to the cell interior and the virus content is released into the cytoplasm of the cell (Adler, Gifford, and Sumner; Schmidt, The HIV Page).  Once inside of the cell in the cytoplasm, the matrix protein of the HIV contains a localization sequence that is recognized by the nuclear import machinery, which docks the complex at a nuclear membrane pore.  This enables the preintegration complex of the HIV lentiviral vector to pass into the nucleus (Amado and Chen, 1999).


LINK:

http://biology.kenyon.edu/slonc/gene-web/Lentiviral/Lentivi2.html

Offline J220

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Re: Poz, but in a good way?
« Reply #9 on: November 09, 2009, 10:24:03 AM »
The title of this thread is misleading because when HIV is used as a vector in gene therapy it is disabled and not infectious, so there is no way that the person can become poz this way.

Excellent point.

As ecstatic as I am that scientists are using hiv's mechanism as a way of treating other conditions....how does that help us?

Sorry, not in a good mood this morning....the hell wth it.
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline Cerrid

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  • only as good as your last haircut
Re: Poz, but in a good way?
« Reply #10 on: November 09, 2009, 12:45:45 PM »
So Aubourg's team removed the genetic parts of HIV that make it dangerous, leaving basically a scaffolding to carry the new therapeutic gene.

If the "scaffolding" still contains gp120 and all the other junk dangling from the HIV shell, then it's possible that the body produces antibodies against it - so technically speaking, the boys could become poz: an antibody test would turn out positive. But since HIV is stripped from its reproductive power, they would be non-infectious and their immune system would not be damaged. It's a small price for an ALD cure, I guess.
"Boredom is always counterrevolutionary. Always." (Guy Debord)

Offline Assurbanipal

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Re: Poz, but in a good way?
« Reply #11 on: November 09, 2009, 02:36:47 PM »
If the "scaffolding" still contains gp120 and all the other junk dangling from the HIV shell, then it's possible that the body produces antibodies against it - so technically speaking, the boys could become poz: an antibody test would turn out positive. But since HIV is stripped from its reproductive power, they would be non-infectious and their immune system would not be damaged. It's a small price for an ALD cure, I guess.

Precisely
5/06 VL 1M+, CD4 22, 5% , pneumonia, thrush -- O2 support 2 months, 6/06 +Kaletra/Truvada
9/06 VL 3959 CD4 297 13.5% 12/06 VL <400 CD4 350 15.2% +Pravachol
2007 VL<400, 70, 50 CD4 408-729 16.0% -19.7%
2008 VL UD CD4 468 - 538 16.7% - 24.6% Osteoporosis 11/08 doubled Pravachol, +Calcium/D
02/09 VL 100 CD4 616 23.7% 03/09 VL 130 5/09 VL 100 CD4 540 28.4% +Actonel (osteoporosis) 7/09 VL 130
8/09  new regimen Isentress/Epzicom 9/09 VL UD CD4 621 32.7% 11/09 VL UD CD4 607 26.4% swap Isentress for Prezista/Norvir 12/09 (liver and muscle issues) VL 50
2010 VL UD CD4 573-680 26.1% - 30.9% 12/10 VL 20
2011 VL UD-20 CD4 568-673 24.7%-30.6%
2012 VL UD swap Prezista/Norvir for Reyataz drop statin CD4 768-828 26.7%-30.7%

Offline Inchlingblue

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Re: Poz, but in a good way?
« Reply #12 on: November 13, 2009, 12:33:25 PM »

As ecstatic as I am that scientists are using hiv's mechanism as a way of treating other conditions....how does that help us?
 

You're right that there is no direct benefit for those of us with HIV but scientific research of one thing can often have indirect benefits on something else. When considering the use of HIV as a vector in gene therapy, this is great for those of us with HIV because it will mean that HIV will be studied even closer and much more will be learned about HIV, which could lead to better treatments and even a cure. And the money for this research will be money earmarked for gene therapy of other diseases so it won't impact research dollars allocated to HIV, it's a win-win.

Just recently scientists in Germany were studying HIV for use as a vector in gene therapy and they stumbled upon important information regarding areas of the genome that HIV avoids. This information could have an impact on HIV treatment and on controlling HIV.

At DKFZ, Associate Professor (PD) Dr. Stephanie Laufs and Dr. Frank Giordano are trying to find out whether AIDS viruses can be used as gene delivery vehicles in gene therapy. Therefore, it is crucial for them to know where exactly HIV integrates into the genetic material of the host cell. This is a critical step in gene therapy, because depending on the position, this process can result in permanent activation of oncogenes or other damage. Therefore, the researchers took a very close look by starting an analysis of more than 46,000 known integration sites of HIV-based gene delivery vehicles that were determined in various gene therapy studies or are available in gene databases.

Continued. . .

LINK:

http://www.sciencedaily.com/releases/2009/11/091112103413.htm

 


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