1. Biology is hard, unimaginably harder than writing a piece of software, for example.
2. The way research is funded is horribly inefficient and in serious need of an overhaul. I'm all for pouring more money into research, but too much research takes place in bloated universities and too little money trickles down to the scientist doing the actual work.
This is so true. The principal investigator model creates huge research groups that are terribly inefficient. Instead of having a small set of agile researchers, it promotes research groups with tons of middle managers and charlatans. Pure rent seekers. I say this after being a researcher in a few of the best universities in the world. It's pretty hopeless.
Feel free to drop me an email if needed. Contact information is in my profile.
As a brief summary, I think keeping research groups small and most funding internal does solve lots of problems. I think you want to avoid at all costs having a principal investigator that publishes 50 papers per year and supervises 20 students simultaneously. Which means he is actually doing none of these things. Just stamping his signature everywhere, and doing a bit of politics to raise funds.
Howard Hughes Medical Institute conducted a long investigation on how to do good research prior to starting Janelia Campus. They looked into very successful institutions (AT&T Labs, LMB, CSHL, etc) and drew some equivalent conclusions to what I stated above [1].
Hoping for you too. It's in my mom's side of my family. I'm fortunate that my mom didn't inherit, but it's a large family so many loved ones weren't so lucky. That's why I studied biochemistry and neuroscience and got a PhD in drug discovery. Unfortunately my adolescent passion met the realities of real world of biomedical research, and now I work at FAANG. I still hold out hope that others will find a treatment someday for people like you and my family.
Wife has a CAG of 45. We're nearby a city center that is part of the trial and it seems like she's met all the criteria to be included so we're hopeful. Not looking forward to the monthly or bi-monthly lumbar punctures but maybe it will postpone some of her symptoms from getting worse.
Huntington sucks. A neighbour of mine got it a long time ago, and in the beginning he just got slightly weird, then his wife left and got custody, then the delusions started setting in and before he really got any help he had killed himself.
2) how would you guarantee that nearly 100% of the target cells get it. The disease is a dominant condition, and by virtue of its putative mechanism a minority of untreated cells could still trigger the problem (though presumably onset might be delayed)
3) I would worry that if you do the CRISPR cut in the wrong place, or at the wrong time, you could instead make the tandem repeats even longer which would make the progression of the disease faster.
4) Outright deletion of the gene is -- who knows. AFAIK all humans have some, low number of tandem repeats and the disease emerges when you have a lot of tandem repeats. IIRC the mouse tandem repeat KO gene model has no side effects but stuff like alzheimer's AB being protective of certain viral brain infections is coming out, so maybe there's some function there? And lab mice aren't really exposed to too many pathogens.
Not an expert, so experts please correct me if I'm wrong:
* CRISPR doesn't do all of the time what you want it to do. It is quite error prone. What's done usually is that you apply it to multiple cells, check each of them, and take the ones where it worked out. Usually only a fraction has the changes that you wanted.
* Many multicellular organisms like humans grow from a single cell called zygote. Furthermore, very early embryos consist of a ball of blastomeres that each, if you isolate them and put them into the right conditions, can form a full organism.
* So the most practical way right now of editing genome of mice or humans is to hijack that stage, to use either multiple zygotes or blastomeres (not an expert, not sure which of the two is actually used) and apply CRISPR to them, then take the successful results and gestate them.
* In mice as well as other animals like zebrafish, this kind of editing is pretty routine already. But in humans, it's never been done except for one Chinese scientist. We don't know at all whether there are any adverse effects of the therapy, something we overlooked, etc.
* Also, the gene can be identified prenatally in a sense that you sequence the genes of an embryo still in the womb but that is only possible at a much later developmental stage than the blastomere stage so your options of editing aren't better than the options you have in a living human.
* There is another option that doesn't involve CRISPR: If your parent has a healthy copy of the gene and a non-healthy one, one can perform IVF multiple times, take one blastomere each from the ball of blastomeres, test them for the bad gene, and gestate the embryos that have only healthy copies of the gene. If every at-risk patient gets such a therapy, this approach is enough to deal with Huntington's disease and many other genetic diseases but it limits you in animal or plant breeding to mendelian genetics, basically making your life harder than it could be if you want to combine multiple beneficial traits. Here, CRISPR based approaches give you a big benefit, as long as you can deal with the anti-GMO crowd.
https://www.medpagetoday.com/neurology/generalneurology/7711...
It's not a cure, but shows the potential to significantly slow, and possible halt (in some), its onset and advancement.
Same therapeutic approach as Spinraza
https://www.nytimes.com/2016/12/30/business/spinraza-price.h...