Re: Why no "love" for SGMO? Because EL turned us into "lepers"
Your point about the question of need for re-treatment is well taken. Upon reflection I realize that I overstated the possibility of not needing re-treatment for other conditions.
I did neglect to consider that with the HIV treatments there is a strong positive selection for the modified cells. With most other treatments there probably won't be such an effect and the lack of that could potentially make a considerable difference in need for re-treatment. In addition, the degree of differentiation of treated cells at the time of replacement would probably make a huge difference to the frequency of re-treatment. What that will be remains to be seen and it might well vary with the condition. There is much to be worked out.
I quite agree with your IMHO excellent analysis of the decision to proceed from the first trial to the second trial of SB 509.
Where I feel that a better decision could have been made was both 1) in the selection of DN as the target for the clinical trials of SB509 (there were other indications and I suspect that some may have been less risky (i.e.: the metabolic pathway not so complex nor subject to so many influences) [but frankly have not studied that enough to be sure, so it's only really a guess] and 2) in the choice of SB 509 itself to do the first clinical trial on. My feeling is that a condition with a much simpler metabolic pathway would have been much better (even with a far smaller potential market) for strategic reasons: in order to avoid exactly what occurred: "the operation was a success but the patient died!": the ZFs worked and the proximate effect was achieved but there was no significant benefit to the patients shown. (Of course had SB 509 passed the trials I would have been wrong and EL would have been a hero. Life's like that. Hindsight is 20/20)
There is very little chance of such a problem with the mono genetic disorders, especially hemophilia: the cascade is extremely sensitive and we already know from many years experience that it is necessary only to achieve low percentages of normal levels of protein to have a pronounced therapeutic effect.
IMHO it is very clear that EL has taken lessons from SB 509 fully into account and is shifting direction accordingly. Considering the excellent job he's done of resisting/minimizing dilution, with the DAS and SIAL agreements, etc he's earned a "pass" for one mistake. No one's perfect.