Is there research for a cure going on right now?

Jun 24, 2015

SC: This is of course the ultimate goal. While many of the new treatments have made great strides in normalizing the lives of patients with HAE the hope is to find a pathway to cure the disease.

There has been a case reported where a 7 year old boy with Evan’s syndrome and concomitant HAE type I had normalization of C1 inhibitor levels and resolution of his swelling after undergoing an allogeneic cord blood stem cell transplant.

BZ: Not to interrupt, but I am sure that Sandra will explain the risk to benefit balance issue here.

SC: Certainly. Stem cell or bone marrow transplantation carries too many risks to be justified for the treatment of HAE. In this case, however, the treatment was justified by the refractory course of the Evan’s syndrome — which is an autoimmunopathy characterized by autoimmune thrombocytopenia and autoimmune hemolytic anemia. This young boy had suffered a severe intracranial hemorrhage and required an emergency splenectomy prompting the decision to perform the bone marrow transplantation.

For us, the importance of the case is that it shows that it is possible to normalize the C1 inhibitor level and cure the disease using hemopoietic cells.

BZ: I agree with your interpretation. We’ve always thought that the liver is the main source of C1 inhibitor, but this case at least raises the possibility that hemopoietic cells can make sufficient C1 inhibitor to normalize the plasma levels. To be fair, I’ve also heard about at least one other case in which an HAE patient received a bone marrow transplant, but did not experience remission of his HAE (not published). Regenerative medicine is a really new field, and there’s a lot we don’t understand about stem cells. I wonder whether it may be necessary to transplant a very particular type of stem cell in order to correct the defect?

SC: Yes, that could be true. I expect that we will be able eventually to identify the specific stem cell or progenitor cell that is required to correct C1 inhibitor levels in HAE patients. Once we know how to identify these cells, we would want a safe way to use the cells to treat patients. Have there been any new developments in this area?

BZ: Absolutely. This has been an exciting area. Tremendous progress is being made in a technique called gene editing. This technique allows investigators to correct specific mutations. It could be possible to isolate this particular stem cell from the blood of an HAE patient, correct the mutation in the laboratory using this technology, then give the patient back his or her own corrected stem cell.

SC: You and I have been interested in studying ways to increase the secretion of C1 inhibitor. Could that be a way to achieve a cure?

BZ: I hope so. As you know, patients with HAE make both normal C1 inhibitor protein and an abnormal or mutant C1 inhibitor protein. Our studies suggest that the mutant protein can interfere with the secretion of the normal protein at least in some HAE patients. Our studies suggest that correcting this interference has the potential of eliminating swelling attacks. Stay tuned.

SC: Yes, I look forward to the solution of ‘the gain of toxic function’ as you have termed it. I always look at it as ‘cellular constipation’ in terms of not secreting the C1 inhibitor. Despite the labels, progress is the key. I look forward to your views on our next ‘question of the week’ and all things HAE as always….

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