Gene Therapy Successfully Treats Teenage Boy with Sickle Cell Anemia

[Ygggdrasil]

*in one patient, for at least 15 months

Research published this week in the New England Journal of Medicine reports on a case of using gene therapy to potentially cure a teenage boy of sickle cell anemia, a genetic disease that impairs red blood cell function:

First, the researchers extracted a stem cell supply from their teen patient's bone marrow, before using chemotherapy to wipe out the remaining stem cells.

Then they used a modified virus to deliver an "anti-sickling" version of the beta globin gene into the stem cells they'd removed pre-chemo. The modified stem cells were infused back into the patient.

Over the next few months, the boy showed a growing number of new blood cells bearing the mark of the anti-sickling gene. The result was that roughly half of his hemoglobin was no longer abnormal.

http://www.chicagotribune.com/lifes...y-sickle-cell-health-0308-20170303-story.html

Of course, there are limitations to the study. They treated only one patient and have only monitored the patient for 15 months. Additional follow up will be required to determine whether the genetically modified blood stem cells will persist in the patient's body over many years. Furthermore, additional testing on many more patients will be required to establish the safety and efficacy of the treatment. In particular, the method of gene modification, lentiviral transduction, will insert the corrected β-globin gene randomly into the blood stem cells. This random insertion carries the risk of disrupting important genes in the blood cells to cause diseases like cancer. Newer, more precise gene editing methods like https://www.physicsforums.com/insights/dont-fear-https://www.physicsforums.com/insights/dont-fear-crispr-new-gene-editing-technologies-wont-lead-designer-babies/-new-gene-editing-technologies-wont-lead-designer-babies/ could minimize these risks in future trials.

The results are a very nice proof of principle for gene therapy, especially after some very tragic failures in the past. However, despite the success in this initial trial, much more work needs to be done before this method of gene therapy will be ready to enter routine clinical use.

Scientific publication: http://www.nejm.org/doi/full/10.1056/NEJMoa1609677#t=article
Popular press summary: http://www.chicagotribune.com/lifes...y-sickle-cell-health-0308-20170303-story.html

 

[Greg Bernhardt]

Newer, more precise gene editing methods like https://www.physicsforums.com/insights/dont-fear-https://www.physicsforums.com/insights/dont-fear-crispr-new-gene-editing-technologies-wont-lead-designer-babies/-new-gene-editing-technologies-wont-lead-designer-babies/ could minimize these risks in future trials.

Why didn't they use CRISPR?

 

[Ygggdrasil]

Not sure. This therapy probably had been in the works for many years before CRISPR was invented, so they probably just went forward with what they had been working on. Patent and licensing issues could have also been involved as the research was sponsored by a biotech company that hopes to commercialize the therapy.

 

[Ygggdrasil]

I came across an interesting article on a group developing a machine to automate much of the gene therapy process in order to make it more accessible to people in the third world:

Just last week, French scientists working with the U.S. biotech company BlueBird Bio described how they’d fixed the gene for sickle cell disease in a boy at a Paris hospital. It was yet another technical success. But no one asked how it would reach those who need it. Most cases of sickle cell disease—about 57 percent of the 300,000 new cases each year—are in Nigeria, the Democratic Republic of the Congo, or India.

In October, Adair demonstrated a new technology she thinks could democratize access to gene therapy. Tweaking a cell-processing device sold by German instrument maker Miltenyi, she mostly automated the process of preparing blood cells with a gene therapy for HIV that her center is also testing. Cells dripped in one end came out the other 30 hours later with little oversight needed. She even added wheels. Adair calls the mobile lab “gene therapy in a box.”

https://www.technologyreview.com/s/603762/this-lab-in-a-box-could-make-gene-therapy-less-elitist/

 

[Ygggdrasil]

This random insertion carries the risk of disrupting important genes in the blood cells to cause diseases like cancer.

Clinical trials of this treatment were halted after two patients treated by the therapy later developed cancer

A company has stopped its clinical studies of a promising gene therapy for the blood disorder sickle cell disease after two people who participated developed leukemia-like cancer. Bluebird bio is now investigating whether a virus it uses to deliver a therapeutic gene caused the cancers, reviving old concerns about the risks of this approach.

It’s also possible the cancers stemmed from chemotherapy the patients received to prepare their bodies for the gene’s delivery. “This is really a sad development whatever the cause,” says Donald Kohn of the University of California, Los Angeles, who has led gene therapy trials for sickle cell and other diseases.

https://www.sciencemag.org/news/202...ease-halted-after-two-patients-develop-cancer

Alternative methods of potentially curing sickle cell disease (using either an shRNA or CRISPR to silence the BCL11a transcription factor) were https://www.physicsforums.com/threads/progress-for-gene-therapy-and-https://www.physicsforums.com/insights/dont-fear-crispr-new-gene-editing-technologies-wont-lead-designer-babies/-against-blood-diseases.997005/. While the shRNA method might be subject to some similar concerns, the CRISPR-based method could potentially be safer (though https://www.physicsforums.com/threads/measuring-off-target-mutations-during-https://www.physicsforums.com/insights/dont-fear-crispr-new-gene-editing-technologies-wont-lead-designer-babies/-gene-editing.967151/ still remain a major safety concern for CRISPR).