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Author Topic: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach  (Read 143561 times)

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Offline geobee

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  • Posts: 266
Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #450 on: June 26, 2014, 12:19:08 PM »
I went in yesterday to Quest to get screened for the Sangamo trial.   As I mentioned before, they are using a laser to blast the wholes in the cells to let the ZFN get in there and do the work of modifying the cell.  So the process is apherisis, modify the cells, put them back in.  Because there are not using a virus as a vector, this should work better as one's body won't be producing ABs to the viral vector.

They have to do a tropism test.  30% of those come back as "no result" b/c there is not enough virus in the blood to obtain a sample.  If I come back as CCR5 only, then I'll be eligible for the trial, which won't be until October/Nov.

Other news:  The monoclonal AB trial is going well.  Most getting UD as long as they are taking it (weekly injection).  Also, CalImmune second arm should be starting soon.  The conditioning is going to be necessary to get the modified stem cells into the marrow.

Offline Jmarksto

  • Member
  • Posts: 468
Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #451 on: June 26, 2014, 04:28:03 PM »
Thanks for the update geobee, and wishing you the best on the test and trial - thank you.

Also, do the monoclonal AB's penetrate the reservoirs?

03/15/12 Negative
06/15/12 Positive
07/11/12 CD4 790          VL 4,000
08/06/12 CD4 816/38%   VL 49,300
08/20/12 Started Complera
11/06/12 CD4   819/41% VL 38
02/11/13 CD4   935/41% VL UD
06/06/13 CD4   816/41% VL UD
10/28/13 CD4 1131/45%  VL 25
02/25/14 CD4   792/37%  VL UD
07/09/14 CD4 1004/39%   VL UD

Offline geobee

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  • Posts: 266
Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #452 on: June 26, 2014, 08:10:25 PM »
I don't know if the AB's penetrate the reservoirs or not.  I'm guessing that they don't.  From what I read before, the virus comes back after you stop the AB treatment.

What a person at Quest did say as that the participants in the study had a favorable view of the injections which allowed them to not take daily meds.  For me, I'd rather take meds than inject myself.




Offline Jmarksto

  • Member
  • Posts: 468
Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #453 on: June 26, 2014, 10:22:57 PM »
Given that the ABs go directly to the blood stream I would expect fewer side effects (even minor ones).  I think I would prefer the injections - even if it was just to eliminate or adjust my lunch schedule a little more.  It would be nice to have the option anyway.

Thanks again for posting, interesting stuff!
03/15/12 Negative
06/15/12 Positive
07/11/12 CD4 790          VL 4,000
08/06/12 CD4 816/38%   VL 49,300
08/20/12 Started Complera
11/06/12 CD4   819/41% VL 38
02/11/13 CD4   935/41% VL UD
06/06/13 CD4   816/41% VL UD
10/28/13 CD4 1131/45%  VL 25
02/25/14 CD4   792/37%  VL UD
07/09/14 CD4 1004/39%   VL UD

Offline freewillie99

  • Member
  • Posts: 306
Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #454 on: July 23, 2014, 11:20:21 AM »
Another article from today's SFGate talking about the Sangamo and Calimmune stem cell trials and their potential to effect a functional cure.

http://www.sfgate.com/health/article/Stem-cell-therapy-could-lead-to-HIV-cure-5640362.php

Stem cell therapy could lead to HIV cure
Erin Allday
Published 5:02 am, Wednesday, July 23, 2014

Two teams of scientists with strong ties to the Bay Area are racing to develop a stem cell therapy that would provide a practical cure for people living with HIV infection, leaving them with an immune system capable of keeping them healthy without daily medication even as some virus remains circulating in their bloodstream.

Both groups of researchers are trying to capitalize on the DNA of so-called elite controllers - people who are naturally resistant to HIV due to a genetic mutation that prevents the virus from latching on to their immune cells. It was an elite controller who donated bone marrow to Timothy Brown, the "Berlin patient," who was the first in the world to be cured of HIV. Doctors attribute Brown's rebuilt HIV-resistant immune system to the genetic mutation in the bone marrow.

Bone marrow transplants are not an effective cure for HIV for the general population because they're risky and expensive. But stem cells, drawn from a patient's own bone marrow and altered to be HIV-resistant, may be able to do the job using the same premise.

"If you could make a person's immune system mutated in a way that HIV could not infect it, then you may be able to cure the HIV," said Dr. John Zaia, a virologist with the Beckman Research Institute near Los Angeles, who's working with Sangamo Biosciences in Richmond on a technique to engineer and transplant stem cells. "That's the premise anyway," he said. "And it's based on that one case in the Berlin, that one transplant."

The teams at the forefront of stem cell HIV therapy are led by Sangamo and Calimmune, a San Diego company that is testing its treatment in patients in Los Angeles and San Francisco.

Calimmune was the first to start human clinical trials, in July 2013, and last month reported that the first group of patients was doing well enough that they were ready to begin treating a second group. Sangamo expects to start clinical trials as early as this fall.

Both groups are being funded in part by the California Institute for Regenerative Medicine, the state's stem cell agency.

The research is based on the discovery in the mid-1990s of a specific genetic mutation that blocks a protein called CCR5. The protein is found on the surface of some cells where it acts as a receptor, allowing HIV to attach and ultimately fuse with the cell. Without CCR5, it's much more difficult, although not impossible, for the virus to infect a cell.

Genetic mutation

In elite controllers, the CCR5 receptor is mutated in such a way that HIV cannot latch onto it. Scientists believe that only about 1 percent of people worldwide have the CCR5 genetic mutation.

Nearly 10 years ago, when Timothy Brown needed a bone marrow transplant to treat his newly diagnosed leukemia, his doctor in Berlin decided to attempt an experiment, and chose a donor who was known to be an elite controller.

Bone marrow contains stem cells that stay active during a person's lifetime, constantly replenishing the cells that make up their blood and immune system. In a bone marrow transplant, stem cells from the donor replace the patient's own stem cells and build a new immune system.

Brown had been HIV-positive since about 1995, and his doctor wondered if replacing his immune system with cells from a donor who was naturally resistant would kill the virus and cure the leukemia at the same time. It worked.

But bone marrow transplants are risky procedures - patients can die from rejection of the donor cells or from infection while their immune system is rebuilt from scratch. They're also expensive and require lengthy recovery. And it's impractical to collect donor tissue only from the rare individuals who are elite controllers.

So bone marrow transplants aren't considered a worthwhile treatment for everyone who has HIV, especially since antiretroviral drugs are so effective.

Instead, scientists believe that they can draw stem cells from the bone marrow of patients infected with HIV, and genetically engineer those cells so that they have the mutated CCR5 receptor. Then, the same cells can be transplanted back into patients, where they will supply the immune system with cells that are HIV-resistant.

'Warrior cells'

"By actually treating the patient's own cells and giving them back, you're essentially helping to engineer an immune system that becomes long-term protective against HIV," said Dr. Louis Breton, chief executive of Calimmune. "The stem cells give the patient a group of highly protected warrior cells to do the job that we want our immune system to do, which is to kill off any disease and virus."

In theory, once the stem cells are implanted in the patients again, they'll be able to indefinitely replenish the immune system, and no further transplants or other treatments would be necessary.

Because scientists don't plan to destroy the patients' old immune system before transplanting the engineered stem cells, patients would continue to make cells that are vulnerable to HIV.

But the hope is that enough of the HIV-resistant cells will be produced that the body will be able to mount an immune response to fight the virus and keep it in check - providing what's called a "functional" cure, in which the virus remains but doesn't cause damage.

"Obviously eradication of all viral strains in the system would be extraordinary," Breton said. "This step we're taking is essentially a one-time treatment instead of lifetime."

The same premise could someday help scientists build a vaccine against HIV. But for now, the two teams of scientists are focused on a specific group of patients - those who aren't doing well on antiretroviral therapy and are at risk of their infection developing into AIDS.

The Sangamo and Calimmune teams have different strategies for engineering their stem cells and transplanting them back into patients. But the basic premise is the same, and the teams are nearly neck-and-neck in their research.

Calimmune was the first to put the stem cells into patients. Sangamo hasn't begun clinical trials with stem cells yet, but earlier this year it reported some success from a study involving transplanted T-cells - a type of immune cell that is destroyed by HIV. The T-cells were genetically engineered to resist HIV, using a technique that Sangamo will apply to stem cells in upcoming trials.

Scientists familiar with the research said they're encouraged both by the premise of the stem cell work and the results that have been produced so far. But even if both teams are successful, the treatment won't be practical on a global scale until it's made much simpler, said Dr. Warner Greene, director of the Gladstone Institute of Virology and Immunology in San Francisco.

Ideal therapy

Ideally, doctors would like to see a therapy in which patients are given a single injection that causes their stem cells to be re-engineered in the body, without having to be removed and treated in a lab. If the ongoing research proves successful in causing a functional cure, Greene said, the next step would be developing a procedure that's much more efficient.

"A lot of the stem cell work involves transplants. As proof of principle, that's great, but when it comes to treating tens of millions of people, it's just not going to work," Greene said. "We always have to have in mind a scalable solution. We must avoid therapies that are only useful to 100 rich people in the world."

San Francisco resident Michael Petrelis said he understands the need to remain wary of any promise of a cure - HIV is complicated, and there may never be a single treatment or therapy that works for everyone to wipe out the disease. But he said hope is something that helps keep him going.

"In addition to my AIDS cocktail, one of the things that's helped keep me alive is my hope for a cure," said Petrelis, 55, who has lived with HIV for more than a decade. "I'm optimistic that I can survive long enough to take advantage of stem cell research or something else.

"A lot of times, the researchers and even people with AIDS say we shouldn't use that 'C' word," he said. "And I'm of the thinking that yes, we should. We have to."
Beware Romanians bearing strange gifts

Offline greenbean

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  • Posts: 20
Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #455 on: July 24, 2014, 02:25:54 AM »
One patient remains off therapy with control viral load for over a year
and another one for 34 weeks.

I think this approach will eventually work. It is just a matter how they can get enough resistant CD4 cells (20-30% is pretty good. the more the better of course).

Hope for the best.

Offline dico

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  • Posts: 72
Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #456 on: July 24, 2014, 04:40:44 PM »
In previous studies, mathematical models have shown that we need at least 50% of our peripheral blood to be changed in order to have a long term remission.

They can change at best 20 to 30% of the PBMC so it won't lead to a cure.

Offline geobee

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  • Posts: 266
Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #457 on: July 24, 2014, 06:19:16 PM »
Quest let me know that I've passed the first round of qualifications for the trial.  One day I may find out for myself whether this works or not!  (Once I start the trial, I'm embargoed from telling the results until it's over).

Offline greenbean

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  • Posts: 20
Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #458 on: July 24, 2014, 08:52:10 PM »
In previous studies, mathematical models have shown that we need at least 50% of our peripheral blood to be changed in order to have a long term remission.

They can change at best 20 to 30% of the PBMC so it won't lead to a cure.

Which study shows that at least 50% is needed? If the study doesn't consider ccr5 mutation even 100% is useless like the Boston patients. Btw both two sangamo patients have experienced longer remission despite having only around 20% cells modified. my feeling is that modifying stem cell is the ultimate cure :)

Also. With the ability to retreat. Mathematically they can achieve over 50% modification with multiple treatments

Offline greenbean

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  • Posts: 20
Re: Zinc Finger Proteins Put Personalized HIV Therapy Within Reach
« Reply #459 on: July 24, 2014, 08:56:08 PM »
Quest let me know that I've passed the first round of qualifications for the trial.  One day I may find out for myself whether this works or not!  (Once I start the trial, I'm embargoed from telling the results until it's over).

Glad to hear that!!! I pray that you will get benefits from it. Hopefully one day I can be in the trial too. Especially the stem cell one

 


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