A long time ago, in a galaxy far far away, ‘visionary’ scientists like Francis Collins thought ‘genetic diseases’ were coming to an end. Because they believed in ‘OGOD’, ‘one gene, one disease’ (lol, *blink*), they were sure identifying ‘disease’ genes would… somehow… give us the ability to cure said diseases.
Unfortunately, even ignoring the technical issues weve had with gene therapy, OGOD isnt exactly how genetic diseases work. Yes, some are caused by one dysfunctional gene, like X-linked ALD I wrote about earlier, but many more are caused by a constellation of genes, environmental stressors on those genes, infectious agents colliding with malfunctioning genes at just the right time…
I dont want you all to get the impression that treating/curing genetic diseases is going to be as ‘easy’ as the previous post made it out to be.
This is the case with a form of blindness– Lebers congenital amaurosis (LCA). People born with this disease progressively go blind in infancy-childhood. There are numerous forms of LCA caused by a combination of 13 genes. Where do you start when youre trying to treat a multifactorial disease? Take small steps. Simplify it.
So they started there:
This gene therapy trial is absolutely nothing like the one I described earlier.
The first one was more elegant– grabbing the positive attributes of three viruses, putting them together for your end goal.
This study is less ‘elegant’ and more ‘brute force’.
They packaged a functional copy of RPE65 into an adeno-associated virus. AAV is a weird little bugger– its not a retrovirus, but it has the capability of inserting its double-stranded DNA genome into our genome. Unlike retroviruses, which insert randomly, AAV actually has this one spot it can insert, in chromosome 19! One spot! And its by accident, virus dont wanna be there. BUT, this virological quirk is something we can capitalize on for gene therapy!
While this insertional quirk has its advantages (the DNA is not going to insert into a tumor suppressor, or activate an oncogene), it also has its disadvantages. The virus dont wanna do it. Insertion is an accident. So to get this virus to work for gene therapy, you have to use A LOT OF VIRUS to increase the odds that this improbably event.
So researchers injected 1.5×1010 to 1.5×1011 viruses directly into one eye of 12 LCA patients 1-2 years ago.
All can now see better in dim light, have an increased visual field, their pupils respond to bright light.
Seven of the 12 have increased visual acuity.
And all of the kids involved… None of them could navigate a small obstacle course scientists set up for them pre-treatment. One video is this cute little boy, nervously twisting his shirt, and just standing there. He was afraid to take one step on the course. He couldnt see anything.
Yeah, after treatment, all the kids could navigate it. That scared kid? Brazenly flies through the course in a minute. No hesitation. And acting like a dopey 10 year old boy.
I teared up watching the transformation, I dunno how the researchers werent bawling.
Its gonna be awesome when gene therapy develops from scientists nervously twisting their lab coats, taking small steps, to us blazing through more complex gene networks without batting an eyelash.