This is promising but needs publication and expert review.
Here's the actual company statement from today:
https://uniqure.gcs-web.com/news-releases/news-release-details/uniqure-announces-positive-topline-results-pivotal-phase-iii
https://www.cgtlive.com/view/huntington-disease-gene-therapy-nets-rmat-designation
The 2023 study is said to have 39 patients (BBC and their recent statement reports 29). The reported findings may be significant but seem small (e.g., low dose: 0.39 of 14.1 points). Earlier they reported composites from the Unified HD Rating Scale, which has the usual caveats for the behavioral and functional sub-measures (vs. the more reliable motor and cognitive). Today's statement instead focuses on the more objective measures instead of the composite.
Earlier, high-dose responders reportedly didn't just stabilize but got better -- unclear how. The more recent findings report that the disability still progressed, but slowed relative to "propensity-matched" controls. (Note 4 of 10 controls opted to join the trial after 12 months.)
Both mention improvement in NfL (neurofilament light chains), which is an objective but nonspecific (and highly variable) measure of the degree of neuronal decomposition. The statement quantifies this at ~8% -- unclear if this level is convincing.
For such an invasive treatment for a slowly progressing, relatively rare disease, they're probably gathering and publishing data as fast as possible. The short-term results seem good, and it will be good to see long-term results over time.
It's possible some effect seen is due e.g., to immune adjuvants or something else during the therapy, and I would want experts to review the propensity matching.
I would be concerned that the micro-RNA produced either also binds with epitopes from other messenger RNA or induces some immune response. Remember, there's no reversal agent or half-life elimination for such genetic treatments.
So: room for hope but also for caution.
Another virus that removes/breaks the inserted gene?
> AMT-130 consists of an AAV5 vector carrying an artificial micro-RNA specifically tailored to silence the huntingtin gene, leveraging our proprietary miQURE™ silencing technology. The therapeutic goal is to inhibit the production of the mutant protein (mHTT)
and the actual announcement: https://uniqure.gcs-web.com/news-releases/news-release-detai...
> 75% slowing of disease progression as measured by Unified Huntington’s Disease Rating Scale (p=0.003)
> 60% slowing of disease progression as measured by Total Functional Capacity (p=0.033)
> 88% slowing of disease progression as measured by Symbol Digit Modalities Test (p=0.057)
> 113% slowing of disease progression as measured by Stroop Word Reading Test (p=0.0021)
> 59% slowing of disease progression as measured by Total Motor Score (p=0.1741)
But I am still reluctant. It's phase 1/2 (ie exploratory) and the phase 3 is the hard part that takes many years. Also it's disease slowing not stopping.
Typical gene therapeutic approaches probably wont work, e.g. Cas9 (you'd need two cuts to delete the sequence), Base editors (cant delete sequence), prime editing (deletion is too large for standard prime editing).
You'd either need a template based system such as homologous recombination (too inefficient) or something like twin-prime editing, but good luck getting that to work on repeat sequence.
There are several episodes of House M.D. that deal with this. Hadleys, one of the doctors, mom had Huntingtons and house hounds her to get tested. She doesn't want to get tested. Really great set of episodes.
I can completely understand how knowing/not knowing would change how you approach life.
I don't ask to strictly bring up politics, but instead to try and address the broad lack of understanding of how medical breakthroughs like this are made.
It's not done just by drug companies. The article says:
> UniQure says it will apply for a licence in the US in the first quarter of 2026 with the aim of launching the drug later that year.
That's true, but that doesn't talk about the tens to hundreds of research papers that have been published over likely decades to make this discovery a reality. And it doesn't talk about how much public money went into this discovery.
Many people reading this article probably have a vague idea that more than just this company was involved, but I feel it is not at all clear to the vast majority of people, since the vast majority of people are not involved in biomedical research.
I wish there was an easy way to figure out how many dollars, how many grants, how many researchers, went into achieving this breakthrough. And that the media would put that into news articles like this. Trace all the citations back a few orders, and I bet you'll find a massive number of NIH and NIHR grants.
There is unfortunately not more massive, bipartisan public outcry in the US over defunding the essential basic research the NIH does... and it's not new to the current administration, since it was attempted to be done back in 2017, too [1].
Scientists need better messaging or else we're going to stop having breakthroughs like this... and the breakthroughs are already going to slow down thanks to things like the $783 million in cuts to NIH grants that the US SCOTUS authorized in August [2].
1. https://pmc.ncbi.nlm.nih.gov/articles/PMC5468112/
2. https://www.scotusblog.com/2025/08/supreme-court-allows-trum...
But, glad to see other Countries funding their research. I wonder in face of one of the largest blunders made by the US, are they increasing funds ?
Folk singer Woody Guthrie wrote the song “old man trump” about fred trump (donny’s dad), while suffering from huntingtons and living in a building owned by fred.
Good science is not political. Politicians making it so are idiots at best and evil at worst. See also "Hanlon's Razor"
Have they never heard of genetic diagnostics? For example with a combination of preimplantation generic testing and in-vitro fertilization you can prevent passing on known genetic mutations to the next generation.
Anyway, they’re just describing the heritability of the disease there.
I hope that we can work towards such a society.
(And of course this research is still worth doing to help the population who already have the illness)
Keep in mind that this isn't a so-called "incompatible with life" genetic issue. People with the defective gene can live asymptomatically into middle age. I've lost multiple family members to HD, and have multiple living with HD today. I would give just about anything to spare them from the effects of the disease. But should we decide, moments into a human being's life, that because they carry this gene, it invalidates their entire existence?
We should indeed keep an eye out for the defunding of medical research but as even a few quick numbers from the NIH (at least speaking for the US) show, it hasn't generally been getting less funding year over year right up to the latest numbers. All the opposite actually. Increases in funding have shrunk slightly, but that's not the same as defunding.
Similar stats apply almost globally in any relevant public funding context. After all, if there's one thing that everyone wants, from rich to poor, powerful or weak, it's to hedge against bad health and a shorter lifespan by whatever means available, and especially if those means involve throwing money that isn't even yours personally at something with publicity.. Even the most selfish politicians can usually get that through the fog of their self-interest.
A misleading data point. This group of people were treated so poorly by the state that something had to be done. I don’t think this is setting a benchmark.
https://haemophilia.org.uk/public-inquiry/the-infected-blood...
I will also say I know the team who wrote the guidelines for use of these therapies. I believe they were mostly finished before the infected blood scandal became a big story. Politics didn't come into it.
I’m in NZ an our system is closely related to the NHS. The funding is where politics comes in and that’s not usually happening at a clinical level, it’s deeply political.
I believe this is the clinical trial they are reporting on: https://clinicaltrials.gov/study/NCT04120493
This trial also appears be open at UCSF...
The risk is that someone else sensationalises the story on your behalf and you don’t get to temper expectations with facts. I think the British researchers did that quite well in the BBC interview yesterday.
I wish the media outlets would mention the fact that at least one of the scientists in this post is an immigrant in the UK. (in this case I’m not sure 1st or 2nd gen)
In the current climate of anti-immigrantion rhetoric around the world, simple things like that might help a little with the perception of immigrants as freeloaders.
Just a thought.
Are we going to rename Polio to The Bill & Melinda Gates Foundation?
And here my government is actively working to suppress mRNA therapies because of fucking politics. Fuck them.
I don't know the details of why AAV5 in particular is their vector of choice in this case, but for whatever reason thats what they've gone with. AFAIK there are no viral or other vectors that consistently infect all brain tissue when injected/ingested, so maybe that's just the best option available. Anyways, it seems that in order to get it to the actual brain tissue that is damaged by the huntington protein (all of it? One particular area?), the best way is to inject it where it needs to go. If you could just pump it into the CSF that would perhaps make things a little bit more tolerable, seeing as you could then just do a spinal tap and inject it that way, but apparently that doesn't work. Or maybe a generalized AAV5 infection has more side effect then targeted injections. Just speculating here.
>It means the decline you would normally expect in one year would take four years after treatment, giving patients decades of "good quality life", Prof Sarah Tabrizi told BBC News.
>The first symptoms of Huntington's disease tend to appear in your 30s or 40s and is normally fatal within two decades – opening the possibility that earlier treatment could prevent symptoms from ever emerging.
My understanding is There's also studies of "duh!" Things, so theres a paper to cite instead of an assumption.
Sure, but it's really sad that scientists need to justify their funding to the public - they already spend so much time justifying it to the NIH and others for funding.
So many people have had their careers jeopardized by finding pulled mid-project. I am really concerned about our research pipeline, because my post-doc friends are all applying to jobs outside the US now.
A spokesperson from (say) NINDS really ought to be shouting to anyone who will listen about how excited they are to see their <many year>, <many dollar> investment in Huntington's pay off.
I'd love it if they highlighted some of the especially "weird" studies that went into this to demonstrate how important fundamental research is and how it goes in unexpected directions.
The (mostly American) public pays their salaries; it's not that odd. The public elect the government (mostly the US government) that distributes the funds. The US voter in general has just got tired of living in the "worst place in the world" while also funding the majority of the world's science and health breakthroughs, I think.
How common a disease is doesn't have much to do with treatment efforts. Cystic Fibrosis has practically been cured by Big Pharma and only ~40,000 people in the entire US have it.
I just would like to say that it's not capitalism that decides if money is invested in a disease or another but just the individuals operating freely in the market. On the other hand Capitalism has been actually the main driver for the massive investments that enable the expensive research in biomedical topics.
It’s unfortunately normal that conditions with very low prevalence, receive less private investment than diseases that affect millions of people. That’s not because of a moral failing of capitalism, but a result of free market and the free decision of the population on where to allocate their resources. Imposing anything else on people would actually be the real moral failing, because what is the right allocation of resources between technological development, investments about hunger, medical development or just leisure? Let each individual decide for themselves and of course feel free to convince anyone to invest in what you consider priority.
So I think the fairest system is the one where individuals remain free to choose how to invest their time and money, while society as a whole can still decide, for example through philanthropy, to give extra support to areas some areas like rare diseases.
Said that, if you know of any organization supporting HD research that deserves any type of donation please let us know here so we can support it voluntarily.
As an aside because I'm pedantic about the language, apostrophes are never used to show pluralism.
Biology is tough in that you can't just "reason" your way to success; it often really does require trying something to see if an approach works.
Very few detractors in the west have any issues with highly qualified immigrants occupying scientific or research roles. Being opportunistic with which kind of immigrants one offers as Good is partly what's aggravating the issue. It's a radical kind of dismissiveness and denialism which is provoking people and ignoring their issues.
The broad western detraction against immigration at the moment is targeted at specific waves of mass immigration with specific compositions that have specific effects on the places those immigrants have landed.
People are primarily concerned about the ability of state, social and corporate institutions to absorb immigrants at this pace and scale without significant zero-sum effects. And, in addition, the significant amount of state support segments of those populations (eg., esp. asylum seekers) have to receive at a time when gov. are under inflationary pressures, debt pressures, etc. and cannot service their own welfare obligations.
Going, "oh but we get good cancer research from immigration!" is so dismissive to these concerns, that the backfire against this messaging is one of the major contributors to people's disaffection.
The idea that people need to be told that there are people who want to immigrate that are in our national interest to absorb, is just plainly absurd. This is uncontroversial and obvious.
> Very few detractors in the west have any issues with highly qualified immigrants occupying scientific or research roles. Being opportunistic with which kind of immigrants [...].
I'm not a detractor of any individual immigrant, certainly not a very skilled one. But I am dumbfounded when I hear people say how wonderful immigration is "for the economy", "for the health system", etc., because we can lure all these bright people over from poor countries with offers they can't get at home.
Like... Mozambique needs good doctors and nurses too. Sudan needs good engineers. Syria needs entrepreneurs.
I don't begrudge the immigrant one bit for moving to get more money or a better life or whatever it is that motivates them, and they sure do contribute to the place they move to. But harvesting the best and brightest minds from poor countries on an industrial scale isn't something that sits too well for me at all. The merits and effects could be debated and disagreed, but it certainly requires much deeper thought than just the greed driven "good for my economy, good for my healthcare, good for me" type quips.
I actually think of it as neocolonialism. The most valuable resource in this day and age is people, and wealthy countries are plundering the human capital from the poor ones like they did with resources in previous centuries. Throwing a bit of charity at them whenever the next outbreak or famine or civil war rolls around doesn't make up for it.
Over a longer view, accepting a construction worker now, because his daughter might cure cancer later, might be an advantageous bargain.
"It's a radical kind of dismissiveness" People keep telling me I'm wrong in the wrong way, if they were nicer I'd consider their opinions. This is an irrational position to stake out, it should go without saying.
"The broad western detraction against immigration at the moment is targeted at specific waves of mass immigration with specific compositions that have specific effects on the places those immigrants have landed."
This is such a laborious way to say "poor, brown or both". Do you get tired of dancing around like this?
"People are primarily concerned about the ability of state, social and corporate institutions"
If you were actually "concerned", you'd advocate for punishing institutions that use cheap (or 'free' if you steal their passport) immigrant labor, rather than targeting those that arrived to fill those positions. Do you have an understanding of why this never happens?
It goes without saying that much of the 'specific immigrant labor' you despise is used to fill the welfare obligations related to care-taking that you are also deeply concerned about.
"dismissive to these concerns" I was assured that 'tone policing' was the domain of the 'woke', yet here it is a second time in the same comment.
"uncontroversial and obvious." You might want to speak to your fellow travelers about which are 'good' immigrants and which are 'bad'. It suffices to say that if they agree in general, but disagree about which group is good, then it is not actually 'uncontroversial'.
Let people draw all the inferences they want about the origins of the scientists involved, but a hamfisted paragraph about a.b scientist being an immigrant from y country does not have a place here.
There has been a strong push back against illegal-immigration in the west. The media has completely reframed the discussion to "How can they be opposed to immigration" because if they said "how can they be opposed to illegal-immigration" their argument would fall apart pretty quickly.
No one with a brain is arguing that immigration doesn't provide tremendous value.
Isn't this also disingenuous? A significant proportion of the groups against immigration are against any immigration and have been floating trial balloons for "remigration" for non-white citizens.
Knowing I could become sympathetic at any point made me more conservative in my career. Once that happened I would have less than five years of earning left. As a kid I wanted to start a business [1], but that was always too risky. Instead I’m the guy who actually considers the employer life insurance options because there’s no way anybody will insure me on my own. I’ve worked at a couple of late stage startups, but I’ve never been part of the early days where payroll is on the line every month.
This could have been mooted by a genetic test at any point. My wife, brother and mother thought I shouldn’t get tested. They’re the ones who know me the best, so their unanimity was influential. But it was my decision all along and I own it.
[0] In hindsight the fact that I never actually acted on a violent impulse should have been reassuring instead of worrying)
[1] what a nerd
We are rapidly and increasingly falling behind at least two other nations in terms of science and health breakthroughs.
The things that make the US seem like the worst place in the world are mostly a result of political gridlock, which is advantageous (in the short term) for a small group of people who thrive under the status quo, who do everything possible with their outsized power to manipulate the electorate to keep it that way, out of cowardice.
The US voter in general has been horribly misinformed, misled and manipulated into supporting things that are both against their own personal interest and against the greater good for the country as a whole.
I don't know how to fix this, but I personally don't think making grand proclamations about how great we are/were while pointing blame fingers around to obfuscate the more obvious reasons for the average citizen's discontent is a smart or ethical way to approach the situation.
Perhaps you are, but I'm not convinced. What's the metric?
> The things that make the US seem like the worst place in the world are mostly a result of political gridlock, which is advantageous (in the short term) for a small group of people who thrive under the status quo, who do everything possible with their outsized power to manipulate the electorate to keep it that way, out of cowardice.
The political lines are clear. You can see endless interviews with kids on college campuses who've been indoctrinated to believe the silliest things. That America is the worst, most racist and sexist place in the whole world.
> The US voter in general has been horribly misinformed, misled and manipulated into supporting things that are both against their own personal interest and against the greater good for the country as a whole.
This seems a tad myopic itself. While I agree people are being misled, I would count both you and I as "people" in that regard, and equally not knowing what's best for everyone. If we did, we could just be the only two voters and it would all be perfect.
> I don't know how to fix this, but I personally don't think making grand proclamations about how great we are/were while pointing blame fingers around to obfuscate the more obvious reasons for the average citizen's discontent is a smart or ethical way to approach the situation.
No idea what this means, as there were no grand proclamations previously mentioned.
I think part of the problem is America can do huge numbers of things right, and carry quite a lot of the advances that help the whole world on its taxpayers' backs, but still be mostly criticised and teased as a country from the citizens of other, generally older, now less high achieving countries. Who only acknowledge those massive, ground-breaking contributions when they are withdrawn and can be used to complain about the USA.
This is not a conclusion I would make without trying to make an anti-immigrant argument.
Rabies?
The brain is slightly elastic, so you'd want to advance a needle glacially slowly (microns/second) into it so it ends up at the right position. The injection itself is also done slowly (microliters/minute) so you don't cause pressure damage.
They might also do some intraoperative imaging (some ORs have MRI or CT machines), which slows things down, and of course there's tons of cleaning and repair work afterward.
Consider that the disease typically manifests in your 30s — does this mean it would begin 4x later (and thus basically never manifest), or that your 15 year progressive decline from ~35-50 would take 4x longer (giving you a normal lifespan, albeit perhaps with some limitations in your later years)?
However, what I want doesn't really matter. It's a democracy, and half of a country will not be ignored. You either listen and find some way to give them what they want in the least objectionable way; or they will take what they want, and take revenge on you for your obstinacy. They will do to you what you insist on doing to them: not listening to you at all as they enact the most extreme form of policies which they agree with.
You speak as if your views express those of a powerful majority who will impose them on your detractors. This a dangerous power fantasy. The castle has been ransacked, the draw bridge is down, and you've no army left.
You either draw up terms of surrender, or they will be drawn up for you.
Well, no, not that either. You're making the same mistake from the other side. The side you say has "no army left" also is half the country. And that half of a country will not be ignored either.
Both sides demand to be listened to, but neither side is willing to compromise or to admit defeat, even temporarily.
So I expect that power will continue to swap back and forth, that when in power both sides will do their best to implement their plans, and when they are out of power they will suffer the other side's vengeance for their obstinacy. I don't see it improving soon. I suspect we'll see at least another two election cycles of this viciousness.
At the moment though, i think there's lots of people speaking as if it were 2022 and all of that ammunition has now been expended and the stores are bare
Mind your p's and q's.
Source: Chicago Manual of Style, 14th edition, section 6.82. Also see section 6.77: Tim had had enough of her "maybe's."
If we're trying to figure out what the most benefit for each taxpayer dollar is, then a rare disease won't win out over, say, cancer research.
Someone may consider researching a rare disease as "waste," even though to everyone including the previous poster who is a widow because of HD, it is far from a waste.
When there is not much of a profit motive to do something - whether going to the moon or fighting a rare disease - public money is the best way to do it. And even throwing a fairly small percentage at it can create big achievements.
And that's one reason I'd like to see how much money and time went into this. We might be surprised that it's fairly small in the grand scheme of biomedical research costs!
in Dutch they are for some words, e.g., 1 ski, 2 ski's. i have no idea how that arose historically.