Don't Say Cure: Questions for Jay Lalezari, MD

 Jay Lalezari, MD

Jay Lalezari is a longtime AIDS researcher from San Francisco. In “We Were Here,” a new film about the early days of the AIDS epidemic, he appears in a photo of the founders of UCSF's legendary Ward 86, the AIDS hospital ward that became a model for the world. These days, he runs dozens of clinical trials on HIV and hepatitis as Director of Quest Clinical Research in San Francisco.

Yesterday morning, February 28, Dr. Lalezari presented groundbreaking data from an AIDS eradication study at the Conference on Retroviruses and Opportunistic Infections (CROI) in Boston.

Sangamo Press Release

We will be blogging the Conference on Retroviruses and Opportunistic Infections, which is happening right now in Boston. But first, we want to post a Sangamo press release. Anyway, more later.


February 28, 2011

Sangamo BioSciences Announces Presentation of Positive Clinical Data From Novel ZFN Therapeutic Approach for the Treatment of HIV/AIDs at Conference for Retroviral and Opportunistic Infections

First Steps in Development of a 'Functional Cure' for HIV/AIDS: Demonstration of Successful Engraftment and Expansion of ZFN- CCR5-Modified T-Cell Product, SB-728-T, with Durable Improvement in Total CD4+ T-cell Counts and CD4:CD8 Ratios

RICHMOND, Calif., Feb. 28, 2011 /PRNewswire/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today the presentation of positive preliminary clinical data from its Phase 1 trial (SB-728-902). The trial is being conducted in immunologic non-responders, HIV-infected subjects who are currently on highly active antiretroviral therapy (HAART) and have undetectable levels of virus but suboptimal CD4+ T-cell counts. The study is designed to evaluate safety and clinical outcomes of Sangamo's zinc finger nuclease (ZFN)-generated CCR5-modified, autologous T-cell product (SB-728-T) for the treatment of HIV/AIDS. CCR5 is the major co-receptor used by HIV to infect cells of the immune system.

"These compelling data provide a mechanistic 'proof of concept' for this novel approach to HIV therapy which shows the most promise of any yet tested," stated Carl June M.D., Director of Translational Research at the Abramson Family Cancer Research Institute at the University of Pennsylvania School of Medicine, and an investigator in a second SB-728-T Phase 1 trial that is led by Pablo Tebas, M.D. at the University of Pennsylvania.

"From a single infusion of ZFN-modified cells, substantial and sustained increases in total CD4+ T-cell counts were observed in most subjects. This improvement is greater than we have seen in any previous adoptive T-cell approach. The data are consistent with CCR5-ZFN-modified T-cells being resistant to HIV infection and having a selective advantage in the presence of the virus — just as we saw in the preclinical studies. This is very encouraging as we continue to evaluate the drug in HIV-infected subjects with active infections."

Summary of Clinical Data

The data demonstrate that a single infusion of SB-728-T was well tolerated; the CCR5-modified cells successfully engrafted in all subjects and resulted in a durable improvement in total CD4+ T-cell counts in five of six of the subjects analyzed. In addition, five of the six subjects also exhibited sustained improvements in their CD4:CD8 T-cell ratio, which is an indicator of immunologic health. The ZFN-CCR5-modified cells also exhibited normal T-cell growth kinetics and trafficking and were observed to undergo selective expansion in the gut mucosa, a major reservoir of virus in the body, suggesting, as predicted, that the cells were resistant to HIV infection. These data represent the necessary first steps in the development of a "functional cure" for HIV/AIDS by providing a protected CD4+ T-cell population in these subjects that is resistant to HIV infection.

http://investor.sangamo.com/releasedetail.cfm?ReleaseID=553112

The clock is ticking.

On Friday, I was in downtown Philadelphia with my colleague Jose Demarco talking to the staff and clients of a local AIDS organization; we have a town meeting this Thursday.  I was explaining the case of the Berlin Patient and the follow up research taking place. People were fascinated, and a small crowd gathered around me. 

One man said, "My partner has that, (the CCR5 deletion that helped cure the Berlin Patient), and we're always trying to enroll in cure studies, but no one seems to be interested." I said that we are going to be collecting a list of people who want to participate in cure research. 

Then I pointed out that many researchers don't realize that people with AIDS still need a cure, since there are effective treatments. The group fell silent. They were stunned--They could not believe that researchers didn't know that they desperately want a cure.  Then there was a flurry of conversation and people wanted to know how they can send a message to researchers that people with AIDS need a cure.

We talked about what it's like to have HIV, even if you have access to AIDS meds. You could have an AIDS-related heart attack, or get lethal liver cancer or AIDS-related lymphoma that your body can't fight off. I have lost friends this way. A lot of people seem to be developing cognitive problems, including dementia. You can get facial wasting, or wasting through your whole body, or a hump on the back of your neck that tells the world you have AIDS. People seem to slide ominously from youth to old age.

Picture these people in the hundreds of thousands.

But the US is only a sliver of the global AIDS epidemic:  We are home to about 1/33 of the people with HIV in the world.  Of the roughly six million people who urgently need AIDS drugs right now, only 20%-30% have access to medication. The others are dying. And we may be at a high water mark for access to AIDS treatment--wealthy countries are cutting funding for AIDS treatment for people in developing countries. Getting treatment will be a struggle for them for the next 50 years, if they are successful. But without treatment now, they won't live to see a cure.

When you think about AIDS cure research, remember this: The clock is ticking. For people with AIDS in the US. And for the millions and millions of people in developing countries who are dying just like it's 1989. We need a cure.

Like the Berlin Patient, except in a mouse, and easier to do.

This is based on information from Jules Levin (www.NATAP.org), who tracks all things AIDS and research.

Basically a California researcher named Paula Cannon has demonstrated that in a mouse, if you treat human stem cells (yes, they're using a mouse that's been engineered to have a human immune system) with a new zinc finger technology, you can disrupt CCR5, which is something that HIV needs to infect cells. The healthy stem cells then reproduce and spread into many kinds of uninfected immune cells. And you don't need to do this to a ton of cells, because these new HIV-free cells you are creating spread quickly. Similar to the Berlin Patient, (he got a special stem cell transplant from someone whose immune system naturally lacked CCR5) but at least in this mouse experiment, a complete stem cell transplantation isn't necessary. Also, if it works in humans, it's a "one shot thing." OK now, we are cooking with gas. Article was in press (and possibly out of reach of most other researchers) for 9 months. Bolding is mine.