15 ms·
First UK child to receive gene therapy for fatal genetic disorder is now healthy
- ryzvonusef 4y ago> Libmeldy is made using stem cells that are derived from a patient's blood or bone marrow and can give rise to different types of blood cells, according to the European Medicines Agency(opens in new tab) (EMA). These stem cells carry the new, functional genes into the body, where they give rise to white blood cells that travel through the bloodstream. > In clinical trials, Libmeldy offered clear benefits to infantile and juvenile patients who hadn't yet developed MLD symptoms; these patients were able to break down sulfatides at normal rates and showed typical patterns of motor development, for example. The benefit of the therapy seemed to last several years, but at this point, "it is not yet clear whether it will persist life-long, and extended follow-up is needed," the EMA noted. > Libmeldy is approved for use in the European Union and U.K., although the U.K.'s drug price watchdog initially rejected the therapy due to its hefty list price of £2.8 million ($3.4 million at today's exchange rates), BBC News(opens in new tab) reported in 2022. The therapy's manufacturer, Orchard Therapeutics, then offered Libmeldy to the NHS at a significant discount. > The gene therapy has not yet been approved by the U.S. Food and Drug Administration(opens in new tab).
- dang 4y agoRelated (somewhat): First gene therapy for Tay-Sachs disease successfully given to two children - https://news.ycombinator.com/item?id=30408104 https://news.ycombinator.com/item?id=30408104 - Feb 2022 (77 comments)
- SamBam 4y agoThe article was skimpy on the details. Can someone explain how this part works? > The new gene therapy [...] works by inserting into the body working copies of the genes that are faulty in MLD, thus restoring the ability to break down sulfatides. How does the new copy of the gene get into every existing cell that needs it? A virus?
- amelius 4y agoAlso, when cells replicate, will the new ones automatically be of the edited type? Or is it not that simple?
- ethanwillis 4y agoIn general it depends. If you modified existing blood cells genotype then it wont persist indefinitely. You'd need to modify the bone marrow. But then some cell lines work like you posed in your question.
- MaryBall 4y agoBecause this therapy edits the stem cells that are found in the bone marrow, it essentially means that the disease is being fixed at the source. Bone marrow stem cells eventually turn into blood cells and immune cells. So if 100% of the cells have been edited, then the resulting cells they turn into will be the edited type.
- janeway 4y agoThat is the goal but not that simple. In most cases, the original disease-causing stem cells are effectively eliminated by the conditioning regimen (high-dose chemotherapy and/or radiation) used before the (autologous) transplantation, so they do not regenerate and cause further harm to the patient. However, in some cases, residual disease cells may survive the conditioning regimen and persist after transplantation, leading to disease relapse. This is more likely to occur in patients with aggressive or refractory disease or in those who receive a mismatched or haploidentical donor graft. To prevent disease relapse, post-transplantation maintenance therapy, such as immunosuppressive drugs or targeted therapies, may be used to eliminate residual disease cells. Additionally, close monitoring of the patient's blood counts and immune system function can help identify and manage any signs of disease relapse.
- herlitzj 4y agohttps://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02017-1/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6... This paper seems to have more details on the actual procedure Patients were treated and monitored according to the schedule described in the appendix (p 17) and as previously reported.16, 17 HSPCs harvested from bone marrow or mobilised peripheral blood (MPB) were transduced with clinical-grade lentiviral vector encoding human ARSA cDNA under the control of the human phosphoglycerate kinase gene promoter.
- jiggawatts 4y agohttps://en.m.wikipedia.org/wiki/Atidarsagene_autotemcel https://en.m.wikipedia.org/wiki/Atidarsagene_autotemcel > The National Centre for Pharmacoeconomics (NCPE) in Ireland recommends "that atidarsagene autotemcel not be considered for reimbursement unless cost effectiveness can be improved relative to existing treatment." Wow… instead of a lifesaving cure they recommend the treatment of the symptoms until the kid dies because it’s cheaper.
- sho_hn 4y agoPeople are often surprised by this, but healthcare and insurance systems assign an explicit numerical value to human lives and run with it all the time. https://en.wikipedia.org/wiki/Value_of_life https://en.wikipedia.org/wiki/Value_of_life
- bcrosby95 4y agoAnything dealing with human lives needs to assign a value to it. You don't want to spend $100 billion on something that's just gonna save 1 person. But spending $100 on something that's gonna save 1 person is something pretty much everyone is fine with. Somewhere in the middle is where most people disagree.
- eternauta3k 4y agoSaying yes to one person's expensive treatment is saying no to 4 people's cheap treatment.
- tialaramex 4y agoIt's not that simple. Economically it's an investment. Twenty years ago I had Hodgkins Lymphoma. Obviously the NHS fixed that. This was doubtless quite expensive, it needed a team of experts, expensive chemicals and radiotherapy machinery. But, if they don't they're out a young productive software engineer because Hodgkins kills people, even assuming you're so callous your response is to just immediately put me down like a dog so as to reduce the cost of palliative care or diverting resources from relatives - Whereas since they fixed it that's maybe 30-40 years of economic productivity and ensuing tax income they're getting. Now, obviously not every such intervention is literally profitable in a financial sense, but I chose my case because even boiled down to simply money this actually can make sense anyway. If you agree it made sense to fix me (and I don't see why you wouldn't) then beyond that it's only about value judgements.
- mmaunder 4y agoI wonder if a similar approach can be used for Von Hippel Landau. “ Mutations in the VHL gene cause von Hippel-Lindau syndrome. The VHL gene is a tumor suppressor gene, which means it keeps cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in this gene prevent production of the VHL protein or lead to the production of an abnormal version of the protein. An altered or missing VHL protein cannot effectively regulate cell survival and division. As a result, cells grow and divide uncontrollably to form the tumors and cysts that are characteristic of von Hippel-Lindau syndrome.” https://medlineplus.gov/genetics/condition/von-hippel-lindau-syndrome/ https://medlineplus.gov/genetics/condition/von-hippel-lindau...
- wbl 4y agoI am not an expert but you would need much more transformation. Missing enzyme in white blood cell is simple: any unreached cells are not a problem. Defective protein in all cells is hard.
- chrisgd 4y agoI think CAR-T and cell / gene therapy is going to cure a lot of these orphan diseases with enough time. They really seem like miracles. Carl June winning a Nobel needs to be a bet on DraftKings. We have seen 10 years of remission with some ALLs in children
- arpanetus 4y agoyou can't just simply state that he's healthy without actually seeing his lifespan
- sobeston 4y agoYou claim to be healthy, yet you have not died yet. Curious.
- mike741 4y agowhere did they claim to be healthy?
- smt88 4y agoYou can be healthy now and developer cancer next year. They're looking at whether this child shows signs of illness, and he doesn't. That's the same definition of healthy that we use for everyone else.
- perlgeek 4y agoThe headline claims the child is healthy, but the article itself says > Roughly six months out from treatment, "Teddi is a happy and healthy toddler showing no signs of the devastating disease she was born with," the NHS statement reads. and later > In clinical trials, Libmeldy offered clear benefits to infantile and juvenile patients who hadn't yet developed MLD symptoms; these patients were able to break down sulfatides at normal rates and showed typical patterns of motor development, for example. The benefit of the therapy seemed to last several years, but at this point, "it is not yet clear whether it will persist life-long, and extended follow-up is needed," the EMA noted. Which is much more nuanced.
- refurb 4y agoYou cant but you can place a very high probability on it. With genetic diseases often the difference between healthy and not is a single enzyme is missing. If you can prove the enzyme level is restored and all the downstream effects match healthy individuals, youve basically restored them to what healthy people are. Durability of the change is the big issue. Some gene therapies wane over time. And of course if damage had occurred before the gene therapy, that may never go away.
- fnordpiglet 4y agoI for one welcome our new genetically modified UK child overlord.
- wheelerof4te 4y agoHow exactly do you edit a gene? Like, it is very, very small thing. How do you even measure it, let alone replace it?
- xen2xen1 4y agoViruses do that an astounding number of times a day, every day, don't they? And this treatment uses a virus.
- yCombLinks 4y agoA virus that we've modified to deliver the genetic payload we want inserted at a specific point in this child's DNA. It's not "give this child a random virus we have laying around, that'll fix her".
- yazaddaruvala 4y agoKeywords to search for "CRISPR Cas9"
- bglazer 4y agoBiochemistry is wild! Measuring is an absolutely fascinating procedure. The predominant method is called sequencing by synthesis. Illumina is the company that basically rules the market for this technology, they have some decent explanatory videos if you’re interested. The first steps are to isolate DNA, then break it into small bits, replicate those small pieces thousands of times, and then anchor these to a glass slide. Then flow a solution over the slide with the individual DNA bases (ATCG) that have been modified to fluoresce when illuminated with a certain wavelength of light. These fluorescently labeled nucleotides get assembled one by one into strands that match the small fragments from the DNA sample. Each time the fluorescent DNA bases are added a laser is shined on the glass slide and a very sensitive microscope camera reads how many strands shone at the frequency that corresponds to A T C and G. This tells you which base just got added to which strand. Repeat a couple hundred times and you have a huge number of sequences of ATCG’s corresponding to each short strand of DNA in the sample. The problem now is assembling these short sequences into a full genome. Basically, the puzzle is finding the arrangement of short sequences that maximizes the overlap between them and their agreement with a reference genome. It’s a pretty interesting problem that (I believe) is classically solved with dynamic programming, although I don’t know the most recent methods. I really don’t think it’s well enough appreciated how integral computation is to DNA sequencing. Signal processing in the camera, assembling the genome fragments, determining whether a mutation exists, and all the subsequent analysis to give biological meaning to a sequence. Edit: editing is a whole other, extremely complicated procedure. In fact, direct editing isn’t really possible now. Instead we can basically just delete and insert.
- TulliusCicero 4y ago> Teddi and her sister Nala, age 3, were both diagnosed with MLD in April 2022, according to the NHS. Unfortunately, Nala was not eligible for Libmeldy because she'd already developed symptoms of the disorder. Holy shit. My god, I'm just thinking of the parents. "Sorry, we can only save one of your kids." "You can't give Nala the treatment?" "Well, we could. We won't, though." I'm sure there are good reasons, but Jesus, that's harsh.
- deleted 4y ago[deleted]
- smt88 4y agoApparently MLD is not in the standard genetic screening panel that these parents would (probably) have been offered. I guess that's one reason for every couple to do genetic counseling if they can.
- ec109685 4y agoIt sounds like it’s not effective if it’s given too late.
- toast0 4y ago> In clinical trials, Libmeldy offered clear benefits to infantile and juvenile patients who hadn't yet developed MLD symptoms Does that mean clincal trials didn't show a benefit for patients who had already developed symptoms? Does it mean it wasn't studied in patients who had already developed symptoms? I don't think it's unreasonable that the NHS won't spend large amounts of other people's money on a treatment that hasn't been studied or wasn't found to be effective.
- perlgeek 4y ago> Does that mean clincal trials didn't show a benefit for patients who had already developed symptoms? Does it mean it wasn't studied in patients who had already developed symptoms? It likely wasn't studied. It's a pretty new treatment, so the vendors start with clinical trials for use cases where the clearest/greatest impact is expected, and maybe later on move to related use cases.
- 627467 4y agoUnrelated: how is it legal for sites to highjack the back button in this way?
- dragold 4y agoNice
- antihero 4y agoFor now
- moremetadata 4y agoThats a new stealth weapon for the global population to watch out for now, knowing how things work in this country.
- Geezus-42 4y agoPlease elaborate.
- moremetadata 4y agoEverything is a double edge sword.
- hypertele-Xii 4y agoThat's the opposite of elaboration.
- moremetadata 4y agoBut thats the response you are getting from me.
- xialvjun 4y ago[flagged]
- Nasrudith 4y agoSaid "stealth weapon" has been running wild for millennia. Our DNA has long been messed with by the environment, well before we knew what DNA or a virus were. The difference is now it is possible to have DNA altering viruses which aren't "almost certainly guaranteed to only do bad things to you".
- moremetadata 4y agoMan has been trying to harness the power of nature for millennia. King Cnut demonstrated it with the tide.
- tw1984 4y agoWe are truly living in a very interesting time. AI is already "smarter" than a big chunk of the population, Musk's company is expected to land human onto the mars soon, gene therapy is able to cure rare diseases that was unthinkable just a few decades ago, a certain type of colon cancer was 100% cured in a trial. Just shockingly amazing!
- raffraffraff 4y agoYup! We're still fucked with climate change though. That one isn't fixable.
- yreg 4y agoIt is fixable, but it will be expensive and we will pay the (much bigger) price at the latest point possible. 'Only' the mass extinction of species part isn't fixable without clarketech.
- concordDance 4y agoDepends on what you mean. Geoengineering can stop global warming if necessary, but bringing back a destroyed ecosystem is effectively impossible.
- heavyset_go 4y ago> Musk's company is expected to land human onto the mars soon I wouldn't make any bets based on Musk's posturing about Mars.
- concordDance 4y agoAdjust for Elon Time. In general if Elon says it'll be done in two years time you can be confident it will take at least 3 years. Average of 4, but possibly more than 10
- c7DJTLrn 4y agoGlad this girl could get the treatment she needed. But I have to question spending millions of pounds on a single dose of a drug at a time when nurses aren't getting payrises in line with inflation and citizens are dying because there's huge waiting list backlogs. Pretty much everybody I know has given up trying to get healthcare if they need it. Of course, it shouldn't have to be either/or. Unfortunately, the institution (NHS) has been driven into the ground and we're all paying taxes for practically nothing in return.
- andromaton 4y agoI think genetic engineering will help countless people. I wonder if the competition will be rogue AI vs genetically improved humanity.