7 ms·
There are a lot of unexplored consequences of potentially editing out a gene as important as PCSK9. Some of the compounds it is making are essential to brain an
by billiam 5y ago
There are a lot of unexplored consequences of potentially editing out a gene as important as PCSK9. Some of the compounds it is making are essential to brain and liver development. They'll have to study that for years.
- ellimilial 5y agoQuite possible. Nobody wants another hERG fiasco.
- whymauri 5y agoDid someone try editing out hERG?!
- ellimilial 5y agoA fair amount of drugs inhibiting it had to be recalled after https://pubmed.ncbi.nlm.nih.gov/16554806 https://pubmed.ncbi.nlm.nih.gov/16554806 and subsequent regulators actions.
- whymauri 5y agoOh, OK -- right hERG inhibition liability is a candidate killer. It's just since the topic was gene editing, I thought someone had experimented with editing hERG somehow which had me really confused.
- tibbydudeza 5y agoether-a-go-go-related ... LOL
- 9dev 5y agoTIL gogo dancers are probably named after a legendary rock club named „Whiskey A Go Go“, which inspired the name of a gene that causes the legs of anesthetized flies to shake similar to once-popular dance moves in said club. Fascinating.
- SV_BubbleTime 5y agoI am aware of the potential promises and discoveries.... and I still think “stahhp” when it comes to gene editing primates. We’ve made it thus far, let’s just not open the box before we really know what’s in it.
- Turing_Machine 5y agoSomeone with cystic fibrosis (or the parents of a child with CF) might well disagree, though.
- SV_BubbleTime 5y agoYep. I agree. It’s a luxury for me personally, but... I do assume there are people with things this could solve that also understand the risks and lean on the side of greater sacrifice/altruism. Here is the thing, this is probably moot. The genie is probably already out of the bottle.
- teachingassist 5y agoAnd they might well not disagree. I doubt that an average person with CF would want testing on primates to be done in their name. Justifying your ethical position by name-checking a disability group is kind of gross, especially given that animal testing is not a mechanism which typically results in improved treatment.
- bigcorp-slave 5y agoHi, not using a throwaway so you know I’m sincere. As someone with a serious and currently incurable disability, I would support testing on one hundred billion non-human primates if it gave me a 5% chance of a cure. I’m sure you’ll find people who don’t feel that way. But I can’t overstate enough how horrible it is to go from being a functional adult with all the joys and sorrows that brings to being a much less functional person in pain every day. That is reality for millions of people. I don’t feel that what GP did was gross. I think it reflects reality for people who suffer on a daily basis, and whose loved ones do.
- carbocation 5y agoThere is at least one example of a healthy adult who is compound heterozygous for loss of function in PCSK9 [1]. Also note that in the study linked in the main post, the gene itself is being base edited in the liver, not globally. 1 = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1559532/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1559532/
- 101001001001 5y agoWe don’t have the ability to measure health yet. People who are by all metrics healthy fall over dead all the time, or have inflammatory/autoimmune problems that get written off as psychosomatic. There are a lot of things that are considered normal today that will later be recognized as diseases.
- carbocation 5y agoWith that perspective, how does one ever go about developing a vaccine or a drug therapy?
- 101001001001 5y agoI don’t understand your question. How do people make vaccines and drugs? By the way, I would like to point out that your ilk have killed a great many people. For decades you have cracked people over the head with the idea that cholesterol is a health outcome and that saturated fat is bad for you. It turns out that cholesterol is a heuristic and that it’s been read wrong to boot. And it turns out saturated fat isn’t just not bad for you, it’s an important part of a healthy diet. https://www.sciencedirect.com/science/article/pii/S0735109720356874 https://www.sciencedirect.com/science/article/pii/S073510972... Dr. Shawn Baker and Dr. Paul Saladino ate nothing but red meat and saturated animal fat for two years and they had CAC scores of zero. There is testimony that someone’s CAC score went down after cutting out sugar and adding beef tallow. Can you blame me for resenting the medical establishment?
- carbocation 5y ago
- elihu 5y agoI'm not an expert so maybe someone can give a better response, but I've understood CRISPR as something that doesn't necessarily edit all the targeted cells, just some proportion of them. So, maybe if one doesn't want to eliminate the production of a compound entirely, one sets the dose low enough to to only edit the genes of, say, half the targeted cells. If I'm interpreting the article correctly, though, it sounds like in their trials they think they may have edited nearly all the targeted cells.
- f6v 5y ago> one sets the dose low enough to to only edit the genes of, say, half the targeted cells Using the single-cell sequencing we’ve learned that disease is sometimes driven by a very small sub-population of cells(e.g. cancer treatment resistance). There’s no way of knowing how the organism will respond to a perturbation even in 1% of the cells.
- refurb 5y agoThere are people with defective PCSK9 genes that appear entirely healthy except for having very low cholesterol. I mean, that's how they discovered the PCSK9 class of drugs.