Promising start to CIRM-funded trial for life-threatening blood disorder

Aristotle

At CIRM we are always happy to highlight success stories, particularly when they involve research we are funding. But we are also mindful of the need not to overstate a finding. To quote the Greek philosopher Aristotle (who doesn’t often make an appearance on this blog), “one swallow does not a summer make”. In other words, one good result doesn’t mean you have proven something works.  But it might mean that you are on the right track. And that’s why we are welcoming the news about a clinical trial we are funding with Sangamo Therapeutics.  

The trial is for the treatment of beta-thalassemia, (beta-thal) a severe form of anemia caused by a genetic mutation. People with beta-thal require life-long blood transfusions because they have low levels of hemoglobin, a protein needed to help the blood carry oxygen around the body. Those low levels of oxygen can cause anemia, fatigue, weakness and, in severe cases, can lead to organ damage and even death. The life expectancy for people with the more severe forms of the condition is only 30-50 years.

In this clinical trial the Sangamo team takes a patient’s own blood stem cells and, using a gene-editing technology called zinc finger nuclease (ZFN), inserts a working copy of the defective hemoglobin gene. These modified cells are given back to the patient, hopefully generating a new, healthy, blood supply which potentially will eliminate the need for chronic blood transfusions.

Yesterday, Sangamo announced that the first patient treated in this clinical trial seems to be doing rather well.

The therapy, called ST-400, was given to a patient who has the most severe form of beta-thal. In the two years before this treatment the patient was getting a blood transfusion every other week. While the treatment initially caused an allergic reaction, the patient quickly rebounded and in the seven weeks afterwards:

  • Demonstrated evidence of being able to produce new blood cells including platelets and white blood cells
  • Showed that the genetic edits made by ST-400 were found in new blood cells
  • Hemoglobin levels – the amount of oxygen carried in the blood – improved.

In the first few weeks after the therapy the patient needed some blood transfusions but in the next five weeks didn’t need any.

Obviously, this is encouraging. But it’s also just one patient. We don’t yet know if this will continue to help this individual let alone help any others. A point Dr. Angela Smith, one of the lead researchers on the project, made in a news release:

“While these data are very early and will require confirmation in additional patients as well as longer follow-up to draw any clinical conclusion, they are promising. The detection of indels in peripheral blood with increasing fetal hemoglobin at seven weeks is suggestive of successful gene editing in this transfusion-dependent beta thalassemia patient. These initial results are especially encouraging given the patient’s β0/ β0 genotype, a patient population which has proved to be difficult-to-treat and where there is high unmet medical need.” It’s a first step. But a promising one. And that’s always a great way to start.

One thought on “Promising start to CIRM-funded trial for life-threatening blood disorder

  1. What Sangamo actually did was knockout the enhancer region of the BCL11a gene in order to upregulate fetal hemoglobin… Fetal hemoglobin is the main oxygen transport protein in the human fetus and it’s production continues in newborns for a few months before getting switched off in favor of producing adult hemoglobin. In healthy people that’s great. But in those with beta-thalassemia or sickle cell that’s when the problems begin.

    So Sangamo edited the patient’s own stem cells, deleting the gene which had turned off fetal hemoglobin production, thereby enabling the body to once again produce fetal hemoglobin.

    As part of the treatment the patient’s bone marrow was wiped out to make space for the edited stem cells. That’s why the patient needed a few blood transfusions to tide him or her over until the edited stem cells started producing enough fetal hemoglobin to end transfusions.

    It’s remarkable because this is a patient with beta thalassemia major, the most severe form of the disease.

    So far Sangamo’s treatment looks to be a lifesaver. The patient’s fetal hemoglobin level has risen to 31% of total hemoglobin. At such levels the treatment would very likely cure sickle cell anemia too.

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