General Updates | What may the future hold for the treatment of sickle cell disease?

I’d say that the holy grail is probably in vivo gene therapy. If we can develop a successful strategy to deliver gene therapy without the need for myeloablation and without the need for apheresis of the patient’s stem cells and transplantation of the stem cells back into the patient, that probably is going to be the most effective treatment, but concerns about cost and access will remain with in vivo gene therapy. So until then, we will need to continue to explore pharmacological approaches. Of course, we do have stem cell transplantation and other gene therapy approaches right now. But again, those remain unavailable to most people living with sickle cell disease worldwide. 

So when it comes to pharmacological approaches, I think that it’s unlikely that we will find a silver bullet, a single drug that successfully targets all complications and all pathogenic pathways. So I believe that treatment will be consisting of cocktails of multiple drugs used either in combination simultaneously or serially in patients, and that it will be biomarker-based with a precision medicine approach so that in any individual patient, we will know what pathogenic pathway is predominant at a certain time or in a certain patient. So does a patient have a higher hemolysis phenotype or does a patient have more hyperadhesion or is ischemia-reperfusion injury predominant in somebody as opposed to another person or are certain inflammatory markers to be targeted. So we know, for instance, we have monoclonal drugs, monoclonal antibodies that target specific cytokines, inflammatory cytokines. And so we should perhaps one day target specific cytokines with some drugs, while at the same time reducing polymerization with pyruvate kinase activators. So there are, I think it’s just going to be a combination approach, really. 

I believe that induction of fetal hemoglobin will remain an important strategy, and I believe that we will have drugs that are cleaner than hydroxyurea in this sense that they induce fetal hemoglobin. I still think that reducing hemolysis will remain beneficial, but I don’t think that either one of these approaches will probably be sufficient to completely reduce the rate of vaso-occlusive episodes. Right now, we know that either one of these approaches only reduce vaso-occlusive episodes by at most 50%. So to bridge that gap to 100%, I strongly suspect that we will need multiple pharmacological, multiple drugs to be used simultaneously or serially.

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