4 ms·

Not quite on topic, but I do believe a way needs to be found to make development of targeted therapies feasible for these ultra rare genetic disorders. The curr

by zmmmmm 5y ago

Not quite on topic, but I do believe a way needs to be found to make development of targeted therapies feasible for these ultra rare genetic disorders. The current model seems to be that they go through the standard clinical drug development pathway which is never going to be economically feasible for something applicable to such small cohorts of patients. The best I can see is to invest very heavily in the common methods underlying how the therapies get created - gene editing, knockout / interference etc. The better these work, the less risk there is that a drug is going to fail at clinical trials. It means, a lot more basic research as well as applied research to translate the findings. Then we need to work on smoothing the clinical trials pathway as much as possible so that if a method is operating from proven principles it doesn't have to jump every single hurdle as if it is completely novel. Obviously, there are huge risks here if it goes wrong. But on the other hand, we can look at the cancer space and see that patients get very ready access to experimental drugs there, and overall it is enormously beneficial to overall progress. Rare disease sits somewhere in the middle - people are not (usually) dying but their life quality is so heavily compromised that there ought to be some allowance for a more accelerated access to trial drugs than if we are talking about routine medical use.

Thebroser 5y ago
The thing about these developmental conditions is that in theory there a lot of different treatment modalities that can be pursued at the embryonic level that could address these conditions (viral or non viral gene therapy, CRISPR based base deletions/insertions of the correct allele, etc.). However, once embryonic development has occurred and these conditions have manifested, it would be very difficult to alleviate them. Note that this is very different from something like sickle cell anemia. As a metaphor, think of the human body as a brick house. Using state of the art biotech to treat sickle cell anemia would be like trying to replace a leaky pipe hidden under concrete in the house. Yes it may be difficult but it is doable as it’s a fairy isolated issue. Trying to fix developmental diseases like KS would be like trying to replace every inch of the mortar in the brick house. It would be painstakingly difficult to do it right without the whole house collapsing. In summary, the tech you are referencing is basically limited to pre-developmental organisms, it needs decades or centuries to go before we may feasibly perform large scale genetic engineering that can undo post-developmental physiology. Next, we have to understand that there are serious ethical considerations on treatments that target embryos. Biology is still very much a black box field. It is near impossible trying to factor in all the parameters in this problem space, especially when you are altering genes at a highly regulated stage of human development. Millions of model organisms like mice and non human primates are used to test therapies, but would we be willing to do the same to human embryos at such a large scale? I would hardly imagine an IRB approving research like this in my lifetime in the U.S.

by zmmmmm 5y ago

Thebroser 5y ago

The thing about these developmental conditions is that in theory there a lot of different treatment modalities that can be pursued at the embryonic level that could address these conditions (viral or non viral gene therapy, CRISPR based base deletions/insertions of the correct allele, etc.). However, once embryonic development has occurred and these conditions have manifested, it would be very difficult to alleviate them. Note that this is very different from something like sickle cell anemia. As a metaphor, think of the human body as a brick house. Using state of the art biotech to treat sickle cell anemia would be like trying to replace a leaky pipe hidden under concrete in the house. Yes it may be difficult but it is doable as it’s a fairy isolated issue. Trying to fix developmental diseases like KS would be like trying to replace every inch of the mortar in the brick house. It would be painstakingly difficult to do it right without the whole house collapsing. In summary, the tech you are referencing is basically limited to pre-developmental organisms, it needs decades or centuries to go before we may feasibly perform large scale genetic engineering that can undo post-developmental physiology. Next, we have to understand that there are serious ethical considerations on treatments that target embryos. Biology is still very much a black box field. It is near impossible trying to factor in all the parameters in this problem space, especially when you are altering genes at a highly regulated stage of human development. Millions of model organisms like mice and non human primates are used to test therapies, but would we be willing to do the same to human embryos at such a large scale? I would hardly imagine an IRB approving research like this in my lifetime in the U.S.