Progress in stem cell therapy for HIV/AIDS

Last week the company Sangamo Biosciences announced good results from their HIV/AIDS trial in which they genetically altered patients' own T-cells. CIRM is following this trial closely, since it's the precursor to one being developed by a team of CIRM-funded researchers led by John Zaia at City of Hope that includes Sangamo.

According to Discover Magazine, the company reported last week:

The goal was to see if receiving these altered cells would let patients go off their anti-retroviral drugs. The results, reported at a recent conference in Chicago, were mixed—the cells didn’t always survive long in the fifteen people enrolled. But two patients saw their HIV levels drop 10-fold, and one patient who stopped his anti-retrovirals first saw a spike in virus levels but then had them decline to undetectable levels.

The work funded by CIRM is a next generation version of this trial. In both cases, Sangamo's technology is used to snip the DNA of cells taken from a patient's bone marrow. Those snips introduce a mutation in a gene called CCR5, which makes the protein that the HIV virus uses to enter a cell. No CCR5 gene means HIV can't infect the cells.

Doctors then reintroduce those cells into the patient. The idea is that the patient will then be resistant to the HIV in their bloodstream and eventually can go off drugs. In the recently reported study, the team altered the adult T-cells, which would supply a finite number of resistant T cells. The CIRM study will be altering the blood-forming stem cells, which give rise to T-cells, in hopes of creating a more permanent supply of HIV-resistant T-cells.

This video gives more information about the goal of the CIRM-funded team:


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CIRM HIV/AIDS disease team technology makes news

Richmond-based Sangamo BioSciences has been making a lot of news lately with their gene editing technology. Theirs is the technique being used in CIRM'S HIV Disease Team Award to John Zaia at The City of Hope (summarized in this San Francisco Business Journal story).

Sangamo's so-called zinc finger technology can recognize a specific location in the DNA, snip it out, and replace it with a different sequence. In the case of HIV, the molecular zinc scissors are being used to create a mutation in a small region of DNA in blood-forming stem cells.

Those cells altered in the lab lack a working copy of the protein CCR5, which the HIV virus uses to enter and destroy immune cells. The team then plans to transplant those altered stem cells into a person, where they create a new immune system that is resistant to HIV infection. Early results from this work in animals look promising and the team is hoping to be able to enter human clinical trials with the technique in the next few years.

This is one of two CIRM disease teams attempting to generate a stem cell-based therapy for HIV/AIDS. The other award, to Irvin Chen at UCLA, is using a different type of molecule to mutate the CCR5.

Ron Leuty of the San Francisco Business Journal had a story yesterday about Sangamo's prospects, which include a trial to treat pain associated with diabetes, called diabetic neuropathy. The technique is also being used in research to treat the blood-clotting disease hemophilia B and to create disease-in-a-dish models of heart disease. Reuty wrote about the heart disease work, being carried out by Sangamo and researchers at the Scripps Translational Science Institute:

Using induced pluripotent stem cells — adult stem cells manipulated to give them embryonic-like qualities — researchers will recreate cells that line the arteries. ...

"Genome editing allows us to do an experiment no one has ever tried — that is, if you change someone's genetics, can you make their cells revert away from acquiring a disease?" Samuel Levy, director of genomic sciences at the Scripps Translational Science Institute, said in a press release.

This video describes how the City of Hope team hopes to use the zinc finger technology in their proposed therapy for HIV.



You can also watch talks by City of Hope research John Zaia, CIRM board member and HIV patient advocate Jeff Sheehy, and HIV advocate Loren Leeds when they spoke to the CIRM governing board about the work.

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Celebrating National Cancer Research Month with a cancer stem cell round-up

In celebration of National Cancer Research Month, our colleagues at Sanford-Burnham Medical Research Institute have posted a series of blog entries about cancer research at their institute. The latest installment includes CIRM grantee Robert Wechsler-Reya, who moved to California from Duke University on a CIRM Research Leadership Award.

According to their blog:

Dr. Robert Wechsler-Reya, who directs the Tumor Development Program in Sanford-Burnham’s Cancer Center, has spent many years studying how “good” processes can also cause disease. He is particularly interested in how mechanisms that are normal in embryonic development can cause cancer when turned on in children and adults.

“We work on the relationship between development and cancer, particularly in the brain,” says Dr. Wechsler-Reya. “We’re interested in how normal stem cells and progenitor cells make decisions like when to divide, when to differentiate and what to differentiate into. We’re interested in how those decisions go wrong in cancer.”

To-date, CIRM has awarded more than $130 million to cancer research, including grantees working to understand the role of cancer stem cells in the disease and other teams working to develop therapies. Among our Disease Team projects, which have the goal of reaching clinical trials by 2014, CIRM funded two teams working on therapies for glioma (City of Hope and UCSF), two working on therapies for leukemia (Stanford and UCSD), and one working on solid tumors (UCLA).

Here are a few resources CIRM offers for people trying to get information about stem cells and cancer.

• Information about stem cells and glioma
• Information about stem cells and leukemia
• Information about stem cells and solid tumors

We also produced this video with CIRM grantee Catriona Jamieson at Moore's UCSD Cancer Center at the University of California, San Diego. Jamieson has a therapy in clinical trial for a pre-cancerous blood condition. The work that led to that trial was funded in part by a CIRM SEED grant.



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City of Hope performs 10,000th bone marrow transplant, works toward therapy for HIV/AIDS

Last week the City of Hope announced performing their 10,000th bone marrow transplant since 1976 when they were among the first centers to carry out the risky procedure. They said:

City of Hope performed its first successful bone marrow transplant in 1976 on a young college student from Indiana who was diagnosed with acute myeloid leukemia. His physician told him he should prepare himself for inevitable death. But his cousin, a physician in Los Angeles, knew that City of Hope was launching a bone marrow transplant program. The young student went to City of Hope to undergo a bone marrow transplant, and he has remained in remission for 35 years.

Bone marrow transplants are the original stem cell transplant because it’s the blood-forming stem cells in the bone marrow that are being transplanted from the donor and that rebuild the blood supply of the sick person. The procedure has dramatically increased survival rates for diseases such as leukemia, lymphoma and myeloma, and in one recent dramatic case also seems to have treated an AIDS patient.

This AIDS patient — widely known as the Berlin patient — received blood-forming stem cells from a person who was immune to HIV. Those cells rebuilt the patient’s blood system with cells that could resist the HIV virus. The announcement of that case was dramatic and exciting. However, there aren’t enough HIV-resistant people to provide transplants for all people infected with HIV. CIRM is funding two teams of researchers — including one at City of Hope — who are genetically engineering blood-forming stem cells to contain the mutation that seemingly cured the Berlin patient. A transplant with those cells could leave patients resistant to the infection and carry less risk because it's their own cells being modified. We should know in a few years whether the FDA considers the research ready to test in humans.

What’s interesting is that the City of Hope announcement about their 10,000th bone marrow transplant is being hailed by some as a victory for adult stem cells. Blood-forming stem cells have by now cured countless people of blood diseases, but they can’t cure diseases of the nerves, liver, pancreas or any organ other than blood. Mesenchymal stem cells, also found in bone marrow, have been tested as therapies in a number of diseases, and they seem to have improved symptoms in some diseases, but they have not been shown to replace damaged tissue or cure the disease.

Scientists have found tissue-specific stem cells in many organs and one day they might be used to treat disease -- and if they do there’s little doubt CIRM will have been involved in some way in that discovery. Some CIRM grantees are already working to develop new therapies with tissue-specific stem cells from brain. But until there’s a cure for every disease that has yet or could one day strike my loved ones, I think it’s too early to claim which stem cell type is best for all diseases.

This video about the City of Hope HIV/AIDS disease team features CIRM board member Jeff Sheehy:




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Stem cell therapy treats HIV, basis for two CIRM disease teams

There’s a lot of buzz today over a paper in the journal Blood declaring a man who has come to be known as the “Berlin patient” cured of HIV.

The same patient was featured in the New England Journal of Medicine in February 2009. A man infected with HIV needed a bone marrow transplant for his leukemia. The doctors gave him the transplant from a person who was naturally resistant to HIV infection. The donor’s bone marrow cells contained a mutated protein called CCR5, which is required for HIV to enter the cell. This follow-up work presents the results of numerous tests that failed to find evidence of remaining HIV infection.

In the paper, the authors write: "In conclusion, our results strongly suggest that cure of HIV has been achieved in this patient."

This story discusses an interview in a German publication in which the Berlin patient discusses the difficulties he faced during the course of the treatment. Although I don’t read German, the English summary of that interview makes it clear that bone marrow transplant is not an easy answer, and that making the transplantation more tolerable needs to be part of a future therapy.

The Berlin patient is the basis for two different CIRM disease teams. Although the therapy was a success, there aren’t enough donors who lack CCR5 to provide bone marrow for all people with HIV infection. Instead, the CIRM groups are removing the patient’s own bone marrow and attempting two different approaches at manipulating those cells to remove CCR5 function. They will then give the modified bone marrow back to the patients, hopefully providing a life-long resistance to HIV infection.

Here are summaries of the CIRM disease team awards at City of Hope and UCLA. We also have a video about the technique, featuring the lead researcher at City of Hope and HIV/AIDS advocate Jeff Sheehy, who serves on the CIRM governing board.



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HIV/AIDS video for World AIDS Day

World AIDS Day seems like a good time to revisit a video we made this year featuring CIRM board member Jeff Sheehy, who is a long-time advocate for HIV/AIDS research:



CIRM is funding two teams of researchers working on different approaches to treating HIV/AIDS (one at UCLA and one at City of Hope). Both involve replacing a person’s blood-forming system with cells that are resistant to infection.

For more background on the work, you can watch a Spotlight on HIV/AIDS by one of the disease team leaders, John Zaia of City of Hope.

All of these resources are available on our HIV/AIDS disease page, along with information about the grants we fund that target HIV/AIDS.

Here's hoping that on this day next year we'll be able to talk about progress being made by the two outstanding teams of researchers working to cure this devastating disease.

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Patient advocates vital to stem cell research progress

Nature Medicine carried a piece Friday by CIRM governing board member Jeff Sheehy, writing about the importance of having a patient advocate voice in biomedical research. Sheehy, who is living with HIV, is a long-time advocate for HIV/AIDS research. He has been on the CIRM board since the beginning in November 2004, and is a vocal participant in CIRM working groups including the group that makes research funding recommendations to the full board (the Grants Working Group), for which he is vice-chair.

Sheehy writes:

The presence of vocal, engaged patient advocates has added an indispensable dimension to the proceedings. In measuring research quality, advocates tend to focus on a project's ability to benefit people—not just drive scientific curiosity—which keeps even basic biomedical research grounded in its ability to produce concrete health benefits.

CIRM’s governing board includes 12 patient advocates representing HIV/AIDS, MS, diabetes (type 1 and type 2), heart disease, spinal cord injury, cancer, Alzheimer’s disease, Parkinson’s disease and autism. Sheehy goes on to say:

... CIRM is made up of patient advocates from a wide spectrum of diseases and conditions who work together to advance therapies across the board. And contrary to critics' assertions, these advocates have not narrowly focused on their own diseases, but have uniformly advocated for the best approaches for moving basic research towards the clinic. They support each other.

Patient advocates serve a powerful role even if they aren’t directly involved in funding decisions. Don Reed has been a vocal supporter of stem cell research since his son Roman Reed suffered a spinal cord injury. He is sponsor of the Roman Reed Spinal Cord Injury Research Act that funds spinal cord research in California, founder and co-chair of Californians for Cures and blogger on his own site www.stemcellbattles.org and for the Huffington Post.

In a recent Huffington Post blog entry about the World Stem Cell Summit he wrote about the importance of patient advocates staying involved in stem cell research at a political level, in order to maintain the U.S. leadership in stem cell research:

But unless we in the patient advocacy community can encourage Congress to pass a stem cell research protection act the dream will have been stolen.

CIRM came about in part because of the passion and support of patient advocates like Sheehy and Reed, and they continue to be a crucial part of the success of CIRM and of the progress made in stem cell research.

Here's Sheehy advocating for a stem cell therapy for HIV/AIDS. CIRM has funded two disease teams (City of Hope and UCLA) focusing on developing therapies for the disease.

Artist inspired by HIV/AIDS therapies

Miracle of Hope I, Dave Putnam

The promise of a cure for HIV/AIDS has inspired activists, researchers and now artists. The image shown here, by Woodside, CA artist Dave Putnam, was donated to Stanford’s Positive Care Clinic in Atherton, CA. It’s one of three 36” by 48” images making up a new triptych depicting Putnam’s interpretation of the body’s triumph over HIV.

Stanford’s Scope blog describes the images:

The acrylics, which hang in the hallway of the clinic, show a cell that is permeated by multiple black dots. These represent the invasion of the HIV protease enzyme, which is essential to survival of the virus. Blue dots on the canvas are used to capture the image of the fighters – the protease inhibitors that stop cell growth. Gradually, the blue dots spread and overtake the nasty enzyme. In the last painting, a bright yellow canvas shines through, as the enzyme is destroyed (though remnants of the virus remain, as current therapies never completely eradicate it).

If the two CIRM-funded HIV disease teams at UCLA and City of Hope are successful, the disease would most resemble the final, less dramatic image. Both teams are trying to replace the person’s HIV-infected bloodstream with a new blood system that is resistant to the virus. This link provides more information about stem cell approaches to treating HIV/AIDS.




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Stem cells deliver anti-cancer therapy to treat glioma

Looks like the FDA agrees with our choice of grantees. They’ve approved a clinical trial based on work led by Karen Aboody (shown in photo) at City of Hope using neural stem cells to target and kill high-grade gliomas. She’s the leader of a CIRM disease team that we funded to develop a second generation version of this therapy.

The clinical trial will test a genetically altered human neural stem cell line with a known tendency to migrate toward tumors. Those cells contain an enzyme, which accumulates where those stem cells congregate in the neighborhood of the tumor. When the patient is given a relatively harmless chemical called 5-FC, the enzyme converts it to an active chemotherapy agent just at the location of the tumor.

In a press release, the City of Hope quotes Karen Aboody as saying:

"Using neural stem cells as delivery vehicles for therapy may allow us to target concentrated therapeutics specifically to tumor sites while reducing the undesirable side effects of current chemotherapy regimens, including toxicity to normally dividing bone marrow, gastrointestinal tract, skin and hair cells."

Bettina Steffen, M.D., who leads CIRM’s disease team program, says Aboody’s disease team project uses the same cell line that’s also used in the trial that just got FDA approval. That means when she’s ready to go to the FDA for her disease team work, there will be prior experience with the cell line. “Hitting all the hurdles to get the cell line approved is actually a huge deal, as this facilitates her path to the clinic with the CIRM-funded disease team program,“ Steffen says.

You can read more about stem cell approaches to treating glioma on CIRM's glioma facts page.

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