Haemophilia A trial results 'mind-blowing'

hemophilia a is a disease caused largely by deficiencies in one specific protein. massive technological breakthroughs in recent years have enabled scientists to deliver genes to human cells to consistently, accurately and sustainably produce specific proteins. so treating diseases like hemophilia a has become tractable

however, autoimmune diseases are much more complex and there is no single protein or molecule that causes the diseases. in type 1, people have been trying to discover 1) the "triggering" event and 2) the autoantigens that cause the disease for years, and it looks like there is no "silver bullet". current drug technology can target only one, or sometimes two, disease-causing molecules, so for a disease where many molecules each play a small part, we dont have the answer yet

there are a few promising type 1 companies (semma, viacyte, others) trying to turn stem cells into insulin producing cells, but those cells are often rejected by the bodys immune system. some other companies are increasing the number of "regulatory T cells", basically T cells that inhibit autoimmunity (caladrius, celgene / delinia, parvus, lilly / nektar); these have shown promise but it isnt likely theyd be curative, as they just stop the autoimmune attack but cant regenerate beta cells that are already lost

if youre interested in type 1 research, diatribe is a great website that aggregates the latest science and presents it in a way that is easy for non-scientists, specifically patients and their families, to understand https://diatribe.org/

We'd likely live in a very different world had it been prevented or curtailed, though it's hard to know what specifically would be different, as even the existence or non-existence of a single person could be pivotal in history.

viruses are useful because they have evolved to insert foreign DNA into host cells. nothing humans can conceivably engineer has come close yet to the ability of viruses to do this

however viruses have also evolved a lot of bad qualities that cause disease. AAV is nice because 1) it is not known to cause disease, 2) only causes a mild immune response (so the body doesnt reject it before it does its work) and 3) is replication defective, so it wont reproduce uncontrollably in your body

all that said, viral vectors are far from perfect. the biggest issue is that you can usually only inject them once. after one injection, the immune system learns to recognize the virus as foreign, and upon subsequent administrations it will kill the virus before it can transfect cells. also, there is some risk that the viral genome can integrate with the host genome in ways that arent ideal.

from what i understand, the liver and the eye are really the only easily targeted specific tissues. the viruses are naturally carried to the liver, and the physiology of the eye enables viruses to get into cells there easily. getting viruses just to the brain, or heart, or pancreas, is much more challenging

aav technology has been around for a while, but there have been many false starts. back in the late 90s there were copmanies delivering genes into the brain with AAVs to treat parkinsons and alzheimers, and the genes got integrated and expressed by the right cells. however, the diseases were too complex for just one gene to cure them. in many ways, the advances in biology are enabling us to find what diseases are "right" for gene therapy, althoguh vector tech has improved as well