The 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?
Yes, it's a virus, specifically a lentivirus, which inserts its own genome into the cells DNA, including the therapeutic gene. Looks like they first extract bone marrow from a patient, apply the virus which adds the gene, then they put the "fixed" bone marrow cells back into the patient (probably after killing most existing bone marrow through some really unpleasant procedures). The re-inserted, treated cells then expand and begin making new cells that have inherited the fixed gene.
In general, gene therapy is probably most useful currently for diseases that affect the bone marrow (and the eyes), because these are two tissues where you can precisely deliver the virus. It's still challenging to control where the virus goes and which cells it infects if you just inject it straight into the bloodstream.
I'm confused how this would reduce disease progression compared to a much cheaper allo bone marrow transplant then if they are only modifying hematopoietic stem cells since a BMT is just doing the exact same thing except with someone else's non affected cells. BMTs are a horrific procedure though so this definitely has an advantage in that regard.
I would also have to imagine they would have to do myeloablative chemo or radiation to make sure the fixed cells propagate more than the diseased cell line.
Edit: read the study, they do give them the same chemo used for normal transplants.
Most recipients don't need to take immunosuppressants at all if they get PBSC or bone marrow transplants. Even if they do, it's short term. Additionally, the allo grafts need to be matched, which if you're non white is not a good success rate. 85%ish of whites get matched, that number gets depressingly low for minorites. On the US registry, only 1 in 400 donors get called. I happen to be one of those donors and a system where I'm not needed is a better one. The best part is no part.
>Previous studies have shown that 30% to 70% of all patients surviving beyond 100 days after HCT require treatment for chronic GHVD,2,4-6 often for more than 2 years.
Re: a better system is where you don't need donors:
Matching involves the now simple (if costly) task of comparing diplotypes at immune system loci involved in self recognition, like the MHC.
What's horrific to me is that matching by race is still a thing! These genes are under diversifying selection. That means that they often do not match the surrounding genetic background. That means that racially driven matching is bonkers.
I was getting at the article giving the impression this somehow cured the disease vs a BMT just slowing progression. I know the whole transplant thing sucks. I've had two transplants, thank you for being on the list :).
The article indicates they don't know. "it is not yet clear whether it will persist life-long, and extended follow-up is needed" - So they can be optimistic without knowing for sure because they don't have a bunch of kids they treated say ten years ago to check on. It seems like this might stick, they hope it will, they can't know yet.
One of my friends gave his wife a kidney which allowed her to get off dialysis, so yeah, thanks to anybody who is willing to do this for someone they don't even know.
Reading the paper [1], the genetically modified stem cells overexpress the ARSA enzyme. This seems to create a ‘bystander effect’ which increases the total body enzymatic activity above some critical threshold sufficient to arrest the disease process. Myeloid cells associated with neuronal structures are probably critical to this benefit. A standard bone marrow transplant doesn’t reach this threshold, and has demonstrated poor efficacy in early onset disease.
Definitely true GVHD sucks. The article gave me the impression that they were saying it was somehow superior at stopping the disease because it said this "stem cell transplants, have sometimes been used to slow the disorder's progression in infants,"
(fyi a decent amount of stem cell transplant survivors do not have to take immunosuppressants for life)
My 3-year-old niece got her eyes treated for some degenerative disease in the same way. It's amazing what science can do now, a few months earlier and she would have gone blind before her next birthday.
So is the idea here that the 'fixed' cells populate the body and form the basis of all future generations of cells that are produced in the bone marrow?
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.
In this specific case CRISPR-CAS9 was used to edit "hematopoietic stem and progenitor cells". This means all modified stem cells (sadly not 100% of them) will from now on produce cells with the gene bugfix applied.
This does not imply that germ line cells were changed and COULD mean the person could still have a high risk of making children with the original gene defect.
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.
In 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.
Because 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.
Yes, you’re right! A lentiviral vector is used to insert the working gene into the patient’s stem cells. Obviously this is a non-pathogenic version of the virus, so it’s ability to make you ill has been essentially “switched off”. However the ability for the virus to insert genetic information into the DNA of cells remains.
> 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).
I 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.”
I 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
I 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.
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.
It is super interesting! I was at a talk where a genetics company used the Smith-Waterman algorithm (1) to perform sequence alignment. Still I believe it took a long time (24 hours?) to perform the calculations. They were working on optimizing the code as doing so could mean a faster turnaround.
A 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".
We have a set of tools that let you determine biological structures (sometimes entirely, sometimes only partially).
We also have a set of tools to modify genes. Some viruses already do this, so we use them. Were also using CRISPR which is based on the machinery of bacteria.
So you use the modification tools to change genes and the analytical tools to prove you did it correctly.
Of course the level of complexity is way higher since your dealing with a living organism and the modification tools (and analytical tools) aren't perfect, so there is a ton of trial and error to do to correctly.
You 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.
You 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.
The 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.
My assertion is that the every change we do towards things like that might involve million results and since it's not a simple logical statement it's rather hard to verify/validate the outcome in a short term due to the nature of dynamic/complex systems.
Glad 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.
> 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.
People 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.
Anything 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.
It'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.
It's worth mentioning that the study in Ireland indicates that the treatment extends life by 14.49 QALYs (average "Total Life-years" moved from 8.92 to 22.74), which is a long way from a cure. If this is truly a cure, and the treated population lives a full life (life expectancy in Ireland is current 82 years, not 23), then this treatment will become cost effective without any change in the treatment or it's cost. The posted article agrees that this is the big open question.
> 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.
They can't possibly know that the drug extends life to "22.74" years, because it has only been approved for use for the last 3 years! This is like asking for 30 years of Kubernetes experience on a job application.
Even if the estimate is accurate, there is a massive qualitative difference between slowly dying horribly for 'x' years and living a normal life for 'y' years. You can't just subtract 'x' from 'y' and come up with a delta and compute based on that.
Reminds me of the studies that showed that Tamiflu is ineffective because it only reduced the duration of influenza symptoms by 1/2 a day on average. Yes, that's true, I've taken it myself and the symptoms continued for about the normal period of time. But it reduces the severity massively. It's like a light switch. The most severe flu suddenly turns into the mildest of mild cold-like symptoms in a matter of hours. But... that's hard to measure objectively, so it is not recommended because the according to a metric that doesn't matter it doesn't work.
The statistics and metrics in medical papers are woeful, which is why it's commonly accepted that 1/2 of all medical research is false.
> Even if the estimate is accurate, there is a massive qualitative difference between slowly dying horribly for 'x' years and living a normal life for 'y' years.
If only there was a measure that was adjusted for the quality of the year. Some sort of quality-adjusted life year.
Yes, it's not a perfect measure (how could any quantitative measure of a qualitative thing be perfect?).
> Even if the estimate is accurate, there is a massive qualitative difference between slowly dying horribly for 'x' years and living a normal life for 'y' years.
The difference in measured in QALYs - quality-adjusted life years. The study attempts to take that into account.
> They can't possibly know that the drug extends life to "22.74" years, because it has only been approved for use for the last 3 years! This is like asking for 30 years of Kubernetes experience on a job application.
Yes, exactly my point. The long-term effects of this treatment are what will make it worthwhile or not. Trying to extrapolate a few years to a full life does not make that an easy exercise.
Governments and non-profits already funded the development of gene therapy. Letting private companies charge money for it and then blocking people who need it from getting it is a policy decision.
In quality-adjusted life years (QALYs), there is an upper limit to the cost of any intervention because the most you can save from one intervention is one life. If the same money can be used to substantially improve the lives of 100 people with other interventions, then the cost-utility analysis may say a particular intervention is not effective.
You might not like the utilitarian approach but this is how the UK measures effectiveness.
If the cost isn’t reflective of real resource/labor consumption, but instead is a rent on IP (which is partially repaying some fixed R&D investment), it’s not so simple.
Let’s suppose a drug company is setting their price to maximize revenue.
Suppose they make the following projections:
They determine that if the treatment price is $10 million above the actual cost of providing the treatment, 5 people will buy it. $50 million total profit.
If the price is set so the profit per treatment is $1 million, 100 people will use it. $100 million total profit.
If the profit per treatment is $100k, 800 people will use it. $80 million total profit.
If the company isn’t factoring in the value of a life saved, they will pick the $1 million price point. If ethicists then just run with that price, they may come to the conclusion that the treatment isn’t cost-effective. However, they are relying on data that’s an output of a process with conflicting values, and that pollutes the result of their calculation. Garbage in, garbage out. The 700 people who didn’t get treated lose out for a pretty bad reason.
We could imagine a policy where the drug companies are mandated to maximize lives saved when setting prices. One might argue that companies won’t develop as many drugs if profits can’t be maximized. We could adjust the policy to subsidize companies for income lost when setting lower prices. Ie. if the drug company picks the $100k price point to save 700 more lives, the government gives them $20M compensation so they can profit like they would have at the $1M price point. That way society spends the same amount of money on this drug, but more lives get saved. I’m sure there’s a lot of challenges in designing a program like that, but the opportunity to save lives makes it seem worthwhile to attempt.
I do like the utilitarian approach, I just think sometimes you need to look outside the box of do A or don’t do A. If the only options were pay for the treatment or don’t, then Ireland might be making the right call by not paying for it.
Ireland could simply let a local company violate the drug patents. A country like the UK could impose conditions such as profit caps on pharmaceutical companies who base their work on publicly funded research. We could reduce the length of drug patents. There are many, many options besides “role over and let pharma companies charge $4 million/treatment when it costs them $1 million.”
From the article: "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."
So it does seem like they've already discounted it heavily.
Do you know that they ended up at a “profiteering” price point, or are you just assuming? And you do have to pay the team of researchers to go on a speculative hunt for a cure for a super low incidence disease, if you want them to do it again in the future. If you then turn around and seize the results, you’re not encouraging them to take the risk next time.
They really aren't that rare, and the reason we don't help all of them is not because of a utilitarian decision not to spend money on public healthcare. If you can get your humanitarianism to move that money from corn subsidies and fighter jets to health spending, more power to you.
3,100 cases a year in all of Europe, and 3,600 cases a year in the entire US. That's pretty damn rare really. And it's a genetic condition, which means we should be working to eradicate the problem entirely by screening parents and gene editing ideally making it both rare and increasingly rare from here out.
This isn't actually true. There are thousands of underfunded causes right now, from rare disease research to homeless treatment programs to education of disabled kids.
If you're spending $4 million on this you're either raising taxes again (and government expenditure is already roughly 50% of gdp in most developed European countries, cant go much higher without destroying the thing thats making the taxes) or you're not rehabilitating 5 homeless people, educating 5 special needs kids and discovering a potential new treatment for 1 rare disease.
What sort of regulation? Make it cheaper by x% per year or we stop using it? Doesn't sound that dissimilar to "make it cheaper than the total cost of the current treatment or we won't use it".
And then instead of reading "that atidarsagene autotemcel not be considered for reimbursement unless cost effectiveness can be improved relative to existing treatment" today, we would have read something like "current regulatory environment precludes research and development expenditures into atidarsagene autotemcel" in some biopharm prospectus a decade ago.
You can't have it both ways and preventing people from making money means, not surprisingly, they will be very hesitant to spend money researching those areas.
This is something people say over and over, I’m not sure of the source.
Even if it were true, turning a discovery into a distributable, replicable, intervention is the opposite of a trivial task.
And yes, our lovely regulatory environment makes it enormously expensive to study drugs and treatment and to get them approved. Who knows how many lives have been lost by this.
When people talk about for example university research driving technology, I think the practicalities of the real world … aka business aka living in 4dimensional reality … are inaccessible to them. They elide all these pesky details which represent like 98% of what it takes to actually do anything.
The problem is, as always, with allocation of resources. If you are running NHS budgets and these treatments cost £1M each(we don't know what price was agreed in the end, but let's say it's £1M per treatment), that's £1.6 billion to treat 1600 kids. £1.6 billion is a lot of money that can save a lot of more than 1600 people if used for other therapies. It's a horrible choice to make of course, but it's the reality of it. Yes of course the government and the country has enough money to afford it - but NHS is given a fixed budget.
No, it would be rationed if you had 100 ambulances and only decided to use 50 for some reason - that's what rationing is. The service is currently at full capacity, but the capacity could always be increased.
> Wow… instead of a lifesaving cure they recommend the treatment of the symptoms until the kid dies because it’s cheaper.
That's the same sort of ethical calculus that goes into deciding the distribution of any life-saving resources.
We can always spend more (resources/social capital) to save more lives/years of life. How do you decide where that line gets drawn?
Most medical systems decide it by looking at the cost of treatment (Dollars, organs, risks), and quantifying years of quality life gained. If you'd like that bar raised, increase the tax rate/insurance costs.
'Save every life at any cost' is not compatible with a world where you have decide whether your budget goes on a low-ROI, or a high-ROI intervention. 'First come-first-serve' is not compatible with a world where you are optimizing for overall positive outcomes.
Do you have any alternative guiding principle for where money in the healthcare system should be spent?
Compromises always have to be made because the world does not have infinite resources. Unfortunate, but true.
One way to allocate resources between all our competing needs is by using money.
You can come up with other systems of allocation, however all systems will be unfair and arbitrary in surprising ways. There is always a need to choose between ugly choice A and ugly choice B, because our resources are constrained.
And this in turn leads people to be against national health care as they are worried that the government will be the one making the decision that it is cheaper to let people die rather then treat them.
In the US, medical insurers are not allowed to deny coverage for chronic or genetic conditions due to the Genetic information Nondiscrimination Act of 2008 (GINA) and the Affordable Care Act of 2010 (Obamacare). Some treatments may require proof of medical necessity, or require that providers and patients try lower cost options first (step therapy).
Rules for life insurers are different and in some circumstances they may deny coverage.
Yes, someone somewhere will be making this decision. It could be insurance, a doctor, nurse, hospital administrator, or family member, or even the affected individual.
People tend to react differently when the learn it's a government bureaucrat making decisions on healthcare. However, people will also howl when they find out it the decision from a cruel penny pinching CEO. These are really difficult problems. How much is too much to save a life?
Such power is already vested in undemocratically governed private insurance companies, no? I can’t imagine any health insurance plan would have covered this treatment.
Private insurers regularly decide to let people die rather than treat them. Plenty of people also just die because private insurers refuse to cover them because of their inability to afford insurance at all.
As opposed to insurance companies making the decision that it is cheaper to let people die than potentially adversely affect shareholder value by treating them?
You have X amount of dollars. You can spend Y percent on healthcare. How do you spend Y to have the greatest benefit? Save 1 patients with a $300,000 gene therapy, or save 1,000 patients with effective treatment for their diabetes.
Until we have unlimited resources, that trade off will always be made.
The fact that there's a time=money=lives equivalency is kinda unintuitive at first glance, but when you think about it for a bit it will become obvious.
That's such a reductive, dismissive take on the issue it's actually offensive towards everyone in this country trying to make the healthcare system work. The government isn't ran by some cartoon villains, and the resources at NHS's disposal are finite - I certainly don't envy anyone whose job it is to make sure they are allocated in the most efficient way that also saves the most lives.
<< The government isn't ran by some cartoon villains
I will make a short quip here. All cartoon villains I saw appear to be fairly capable administrators. If government was ran by one of those, we would likely see an improvement. I am not sure who is in charge anymore, but I can agree with you that it is not cartoon villains.
I think a full time caregiver of someone incapacitated should have the power to vote on their behalf. This is a big chunk of society, yet seemingly invisible to politicians. Perhaps, if people with disabilities and illnesses couldn't be just ignored as "non voters" they would be more of a priority.
But....they can? You can give someone else the power to vote on your behalf if you cannot do it yourself. Unless you mean that if someone is literally unable to make any decisions by themselves their caretaker should be able to vote on their behalf how they think this person would vote? That doesn't strike me as a very reasonable system, you can't know how someone would vote unless they tell you, and to assume you can or should know is irresponsible.
Yeah I can see there are many sides, as a society we an interest in keeping elections fair, with one person one vote being a good maxim.
But consider the case of a parent of a child with profound disabilities, that child is now an adult of voting age. Wouldn't a person with disabilities have an interest win voting out a candidate / party who constantly rails against providing funding for disabled services? Why should anyone be disenfranchised because of their disability? Its still one person one vote, just in this special case two adults two votes.
>>Wouldn't a person with disabilities have an interest win voting out a candidate / party who constantly rails against providing funding for disabled services?
Sure, but the point is, you don't know this - you can only reasonably guess. And to make a vote on behalf of another person, by effectively guessing what they might want, does not sit right with me.
In Europe they have these things called planes, it's like a tube you enter and sit for a few hours and once exit you are in a driving distance to American hospitals where you can pay and receive the same treatment as everyone else without nationalised healthcare.
What's more, Europe also has these private hospitals which aren't connected to the national healthcare system and which will provide you with top level care if you are willing to pay, no travel to US necessary. Private health insurance (gasp!) is also a thing, should you want to partake in that system.
Europe consists of many countries, and one of them is more than happy to take 9% / 5% of your income in exchange for one quite crappy public health care system - think whenever you need to see a specialist, you have to pay with your own money anyway (or wait months, years to get an appointment). If you want private health insurance, you have to fund the super expensive good for nothing public one anyway.
In the UK I earn a decent wage (well more than 80% of people in the UK), and last year I paid less than £3k / $3.5k for healthcare which covered me, my wife, my 2 children. It also covers my 70+ year old mother and my 90+ year old grandmother who don't earn enough to pay income tax.
80% of people pay far less than I do.
What type of health insurance can I buy in the US for $290 a month to cover a family with no co-pays.
>>you have to fund the super expensive good for nothing public one anyway.
My father had battled cancer in Polish oncology hospitals and has received nothing but top tier treatment wherever he went. What's more, NFZ completely funded the treatment with then-experimental Glivec for him, which was billed at around 200k zł/year(in US, a year of Glivec treatment is around $100k). In the course of 8 years of cancer he had to stop working due to the ilness, and yet was still fully covered and received the same treatment as always.
So no, it's not "expensive but good for nothing". It's not expensive compared to private treatment, and it's extremely good if you have a major ilness. I agree that routine treatment and appointments are in shambles, but that's universally true pretty much everywhere in Europe right now, the waiting times in countries with public healthcare systems have inflated into infinity due to a combination of factors. But even in Poland, I wouldn't dare to not pay into the system - it's too good not to pay for it(and I do, in fact, pay for it).
I'm sorry, I have been lucky to only have limited experience with the system to date and it did not make a good impression. I take it back but I still think that 5 - 9 % of income before tax for healthcare is outrageous.
> but that's universally true pretty much everywhere in Europe right now, the waiting times in countries with public healthcare systems have inflated into infinity due to a combination of factor
I have heard that's not the case in Germany and the private appointments are almost not a thing. I could be wrong though.
It's relevant because sure you can get a private insurance but you are already spending 5% of your income before tax on the public one and can't opt out from it. Like that's too much expenditure already to think about private health insurance.
Indeed. In the UK at least there are a number of private hospitals largely marketed towards international customers where it'd be cheaper for American to come for treatment in many instances compared to getting treatment in the US.
Of course we are, that’s how a mole was removed when someone was playing harp for me.
So, depending on where you are, private healthcare means the government pays their share and you pay the rest through an insurance or directly. Again depending on where you are the insured is often provided by your employer, so if you happen to get ill you can have your treatment in a luxury.
Its sticker price is actually $3.8 million. At that price, it could be administered to every child in the UK with the disease at about the cost of 1 year of the UK's defense budget.
Now you're trading off against the defence of Ukraine (for example). How many Ukrainian soldiers lives is this child's life worth?
I think a big problem is you don't currently realise just how many different worthy causes are currently underfunded. At a guess you could probably spend a couple of trillion a year in the UK before you've exhausted most of the nice things that could be done. There are sooooo many good things to do and only so many person hours (which is what money pays for mostly) to do them.
If you did scrap the defence budget then the money shouldn't go on treating these kids but instead should be invested in the surgery backlogs, ambulance wait times and the justice system trial backlog.
The thing that tires me about this old chestnut is that it’s just a shell game and not actually a substantive idea. “Just take money from somewhere else.” It’s akin to saying that we will use the latest AI technology and machine learning to make our value proposition work. It sounds satisfying but it says nothing.
There is no free lunch but money is not a constraint. Physical resources are a hard constraint. Labour is a hard constraint. Money is not.
Inflation caused by excess money supply (NB: not inflation caused by excess money velocity) cannot survive taxation. Taxation destroys money supply.
It’s no more (or less) complicated than any of the thousands of other fiscal decisions a government makes every year.
There’s a fallacy alluded to in the statement “it’s a very complicated problem” - the allusion is to one of inaction being a safer default choice but nothing about inaction in the face of a complex problem guarantees against making things worse
By qualifying with “complex” problem i mean a problem that’s as complex as choosing what to fund in a national budget. A problem for which no answer can be proven correct. A problem which can only be addressed by taking a considered view on risk. A problem with unresolvable uncertainties.
The real constraint is indeed what that money buys, e.g the aforementioned person hours.
And if you print money and inflate then the price of goods rises. So sure, you might only pay a bit more for the treatment but now fruits are more expensive and your population gets slightly more unhealthy.
So you are actually proposing to raise taxes. The problems is that everyone hate that, and will avoid paying taxes and/or vote for the opposition party.
It depends - in the specific scenario of an incredibly expensive drug for small numbers of patients (and other problems with similar dynamics) then tax might not be the best solution. But in other cases yes.
In this particular case the returns would go to successful investors - not historically a money user class prone to causing inflation (quite the opposite). In this case you may find that you don’t need any intervention - they might take their winnings and go speculate on more investments (great!). It may be that conditions are such that they don’t presently fancy investing, perhaps you could offer them inflation tracking risk free gilts/tbills to park in for now. However you would need to be ready for their choice to go on an inflationary non productive consumption spree. In which case - directed taxation should be applied.
It's probably cheaper if you're buying it in that sort of quantity. Three million quid on this, three million quid on that, three million quid over there, soon you're talking about a lot of money.
If you buy 1600 doses of it at a time they're going to sharpen the pencil for you.
> 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.
The treatment works on the child without symptoms because in most cases neurological affections are irreversible. Since the child had not developed them, the therapy would essentially fix the body before it caused them.
In the case of the child who already shows neurological symptoms, the treatment can help stop the progression of the disease, but most likely not reverse the already existing damage. However, there are already treatments approved to help stop the progression of the disease, including enzyme replacement therapy (provide the enzyme in charge of degrading the sustrate through the bloodstream every so often).
Some would argue that if treatments with similar outcomes already exist and are approved, it could be unethical to test this experimental treatment on a patient (I disagree).
> 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.
> 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.
Apparently 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.
Said "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".
We 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.
> 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?