Huntington's disease treated for first time

2025-09-2411:37698119www.bbc.com

One of the most devastating diseases finally has a treatment that can slow its progression and transform lives, tearful doctors tell BBC.

James GallagherHealth and science correspondent

BBC/Fergus Walsh Two scientists, Professors Ed Wild and Sarah Tabrizi, are pictured from the shoulders up. They are both smiling and wearing white lab coats. Prof Wild on the left has a tightly cropped beard. Prof Tabrizi on the right has long wavy hair. They are clearly in a laboratory with scientific equipment on shelves in the background.BBC/Fergus Walsh

Professors Ed Wild and Sarah Tabrizi led the UK part of the trial

One of the cruellest and most devastating diseases – Huntington's – has been successfully treated for the first time, say doctors.

The disease runs through families, relentlessly kills brain cells and resembles a combination of dementia, Parkinson's and motor neurone disease.

An emotional research team became tearful as they described how data shows the disease was slowed by 75% in patients.

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 new treatment is a type of gene therapy given during 12 to 18 hours of delicate brain surgery.

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.

Prof Tabrizi, director of the University College London Huntington's Disease Centre, described the results as "spectacular".

"We never in our wildest dreams would have expected a 75% slowing of clinical progression," she said.

None of the patients who have been treated are being identified, but one was medically retired and has returned to work. Others in the trial are still walking despite being expected to need a wheelchair.

Treatment is likely to be very expensive. However, this is a moment of real hope in a disease that hits people in their prime and devastates families.

BBC/Fergus Walsh Jack May-Davis is smiling and is wearing a pale blue shirt. He is standing on a street with green hedges and a row of cars blurred in the backgroundBBC/Fergus Walsh

Jack May-Davis has the gene that causes Huntington's disease

Huntington's runs through Jack May-Davis' family. He has the faulty gene that causes the disease, as did his dad, Fred, and his grandmother, Joyce.

Jack said it was "really awful and horrible" watching his dad's inexorable decline.

The first symptoms appeared in Fred's late 30s, including changes in behaviour and the way he moved. He eventually needed 24/7 palliative care before he died at the age of 54, in 2016.

Jack is 30, a barrister's clerk, newly engaged to Chloe and has taken part in research at UCL to turn his diagnosis into a positive.

But he'd always known he was destined to share his father's fate, until today.

Now he says the "absolutely incredible" breakthrough has left him "overwhelmed" and able to look to a future that "seems a little bit brighter, it does allow me to think my life could be that much longer".

May-Davis family An old family photograph of Fred resting his head on his hand with a young Jack in his lapMay-Davis family

A young Jack with his father, Fred, who died of Huntington's disease.

Huntington's disease is caused by an error in part of our DNA called the huntingtin gene.

If one of your parents has Huntington's disease, there's a 50% chance that you will inherit the altered gene and will eventually develop Huntington's too.

This mutation turns a normal protein needed in the brain – called the huntingtin protein – into a killer of neurons.

The goal of the treatment is to reduce levels of this toxic protein permanently, in a single dose.

The therapy uses cutting edge genetic medicine combining gene therapy and gene silencing technologies.

Graphical illustration of how the therapy works separated into four tiles. The first shows a spindly brain cell with a zoomed-in section showing a DNA double helix in blue with a red section denoting the mutated DNA and the build up of toxic protein, also red, inside the brain cell. Tile 2 shows two neurons and hexagonal viruses with a purple line in the middle. Tile 3 shows a close-up of the neurons from before with the viruses inside and releasing their purple squiggly line. Tile 4 goes back to the same zoomed-in view of a neuron, but this time the purple squiggles are sticking to the previous genetic code so there is less toxic protein being made, represented by it being shaded out.

It starts with a safe virus that has been altered to contain a specially designed sequence of DNA.

This is infused deep into the brain using real-time MRI scanning to guide a microcatheter to two brain regions - the caudate nucleus and the putamen. This takes 12 to 18 hours of neurosurgery.

The virus then acts like a microscopic postman – delivering the new piece of DNA inside brain cells, where it becomes active.

This turns the neurons into a factory for making the therapy to avert their own death.

The cells produce a small fragment of genetic material (called microRNA) that is designed to intercept and disable the instructions (called messenger RNA) being sent from the cells' DNA for building mutant huntingtin.

This results in lower levels of mutant huntingtin in the brain.

UCLH The images show two cross sections of the human brain in black and white side- by-side. You can see the semi-circular outline of the skull. Inside is the folded brain matter. The key difference between the two images is the greater amount of dark space on the right demonstrating where brain tissue has died.UCLH

Two brain scans side-by-side. The one on the left is healthy, the one on the right shows loss of brain matter as neurons die in Huntington's disease.

Results from the trial - which involved 29 patients - have been released in a statement by the company uniQure, but have not yet been published in full for review by other specialists.

The data showed that three years after surgery there was an average 75% slowing of the disease based on a measure which combines cognition, motor function and the ability to manage in daily life.

The data also shows the treatment is saving brain cells. Levels of neurofilaments in spinal fluid – a clear sign of brain cells dying – should have increased by a third if the disease continued to progress, but was actually lower than at the start of the trial.

"This is the result we've been waiting for," said Prof Ed Wild, consultant neurologist at the National Hospital for Neurology and Neurosurgery at UCLH.

"There was every chance that we would never see a result like this, so to be living in a world where we know this is not only possible, but the actual magnitude of the effect is breathtaking, it's very difficult to fully encapsulate the emotion."

He said he was "a bit teary" thinking about the impact it could have on families.

The treatment was considered safe, although some patients did develop inflammation from the virus that caused headaches and confusion that either resolved or needed steroid treatment.

Prof Wild anticipates the therapy "should last for life" because brain cells are not replaced by the body in the same manner as blood, bone and skin are constantly renewed.

Approximately 75,000 people have Huntington's disease in the UK, US and Europe with hundreds of thousands carrying the mutation meaning they will develop the disease.

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. Conversations with authorities in the UK and Europe will start next year, but the initial focus is on the US.

Dr Walid Abi-Saab, the chief medical officer at uniQure, said he was "incredibly excited" about what the results mean for families, and added that the treatment had "the potential to fundamentally transform" Huntington's disease.

However, the drug will not be available for everyone due to the highly complex surgery and the anticipated cost.

"It will be expensive for sure," says Prof Wild.

There isn't an official price for the drug. Gene therapies are often pricey, but their long-term impact means that can still be affordable. In the UK, the NHS does pay for a £2.6m-per-patient gene therapy for haemophilia B.

Prof Tabrizi says this gene therapy "is the beginning" and will open the gates for therapies that can reach more people.

She paid tribute to the "truly brave" volunteers who took part in the trial, saying she was "overjoyed for the patients and families".

She is already working with a group of young people who know they have the gene, but don't yet have symptoms – known as stage zero Huntington's – and is aiming to do the first prevention trial to see if the disease can be significantly delayed or even stopped completely.


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Comments

  • By w10-1 2025-09-2417:083 reply

    (non-expert)

    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
    
    There's also a June 2024 article:

        https://www.cgtlive.com/view/huntington-disease-gene-therapy-nets-rmat-designation
    
    That explains a bit more: (1) neuro-surgery introduces gene-virus to putamen and caudate nucleus; (2) virus delivers gene that produces micro-RNA; (3) the micro-RNA blocks the messenger RNA of the bad gene, reducing bad protein production.

    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.

    • By RataNova 2025-09-258:40

      Even getting any objective signal in a disorder like Huntington's is huge, considering how bleak the landscape has been. But yeah, expert review and more transparent data (especially on those control comparisons) are essential before we celebrate too hard.

    • By cogman10 2025-09-2419:181 reply

      If the approach works, wouldn't this also be really good news for other progressive generic disorders?

      • By robbiep 2025-09-255:38

        Huntingtons is not unique but certainly notable because it is caused by repeat sequences and therefore uniquely suited to mRNA silencing in this manner. There are very few other progressive (and I presume you also mean neurological) conditions, but also applied to the rest of the body, where this is the pathophysiology. For example, currently there is no immediate expansion of this to ie Parkinson’s (different pathophysiological basis) Lewy body (although maybe?) alzheimers (again possibly depending on whether it is tau, amyloid beta or simply ‘type 3 diabetes’) and nothing whatsoever for vascular dementia or ALS

    • By meindnoch 2025-09-2421:282 reply

      >Remember, there's no reversal agent or half-life elimination for such genetic treatments.

      Another virus that removes/breaks the inserted gene?

      • By vibrio 2025-09-2422:09

        The bane of most gene therapy research is lack of persistence. With how serious and morbid HD is, I’d guess patients will take their chances.

      • By Den_VR 2025-09-255:03

        Mentioning that might have just been Guardrails…

  • By petesergeant 2025-09-2412:055 reply

    More information on the approach: https://www.uniqure.com/programs-pipeline/huntingtons-diseas...

    > 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)

    • By sleight42 2025-09-2414:281 reply

      It always seemed that an mRNA treatment was going to be the way forward for treating HD, speaking as an HD widower.

      And here my government is actively working to suppress mRNA therapies because of fucking politics. Fuck them.

      • By AudiomaticApp 2025-09-2419:13

        This isn't an mRNA treatment. The m in mRNA stands for "messenger", not micro. mRNA covid vaccines don't mess with the genome anything like this treatment does, and indeed, this treatment is much more dangerous than any vaccine would be.

    • By bjornsing 2025-09-2412:195 reply

      Why does it have to be delivered through brain surgery?

      • By Sebalf 2025-09-2412:442 reply

        The major hurdle of current gene therapies is delivery to the tissue where the defective gene product is causing damage. For instance lipid nanoparticles are only being used to deliver gene therapies to the liver, because if you inject them they just end up there and not much anywhere else. In this case they are using an virus called "adeno asociated virus 5" (AAV5), which does not naturally infect the brain AFAIK. The blood brain barrier (basically just extra impermeable blood vessels), as well as other immunological features in brain tissue, evolved specifically to keep the brain as unaffected as possible from anything bad going on in the body, seeing as any infection/poisoning of the brain is varying degrees of catastrophic and would easily kill you in the ancestral environment.

        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.

        • By meindnoch 2025-09-256:57

          >AFAIK there are no viral or other vectors that consistently infect all brain tissue when injected/ingested

          Rabies?

        • By bjornsing 2025-09-2413:391 reply

          I guess it needs to get across the blood-brain barrier. But that shouldn’t take 10+ hours of surgery, I don’t think.

          • By mattkrause 2025-09-2414:32

            Surgery can be slow, and brain surgery doubly so.

            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.

      • By adcoleman6 2025-09-2412:341 reply

        I’m assuming the viral vector can’t pass the blood-brain barrier.

        • By bjornsing 2025-09-2413:311 reply

          But it doesn’t take 10+ hours to surgically get a virus across the blood-brain barrier, right?

          • By devilbunny 2025-09-2413:51

            The video specifies that the drug is infused over 8-10 hours. Probe placement - again, as depicted in the video, because I don’t see a real methods section - should take about 1-2 hours. The video isn’t clear if this is interactive MRI or just a preop scan that is then loaded into a stereotactic navigation system in a regular operating room, but the former would add another hour at least. MRI is not fast.

      • By jmcgough 2025-09-2413:32

        The brain-blood barrier typically only allows small, non-polar molecules to pass through into the brain, which complicates a lot of neuro/psych treatments.

      • By JoshTriplett 2025-09-2412:34

        Guessing: bypassing the blood-brain barrier.

    • By qnleigh 2025-09-2416:01

      Thanks for sharing this information. Do you (or anyone else here) know if these trends might be expected based on how the treatment works? For example, given than the treatment is only injected into certain parts of the brain, could we expect that some aspects of the disease will be treated better than others?

    • By saretup 2025-09-2412:461 reply

      What does 113% slowing mean? I thought if the speed is x then 80% slowing means the speed is now 0.2x

      • By nicoburns 2025-09-2412:521 reply

        Perhaps it means the effects of the disease are actually reversed?

        • By tkfoss 2025-09-2413:11

          "The data also shows the treatment is saving brain cells. Levels of neurofilaments in spinal fluid – a clear sign of brain cells dying – should have increased by a third if the disease continued to progress, but was actually lower than at the start of the trial."

    • By basisword 2025-09-2412:151 reply

      What do those progression numbers mean in terms of outlook? For example, if someone is treated before showing symptoms (as they know they inherit it) is the progression slowing enough to give them a normal life expectancy and quality of life?

      • By CookiesOnMyDesk 2025-09-2412:311 reply

        It’s covered in the article

        >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.

        • By didgeoridoo 2025-09-2412:461 reply

          I don’t think this quite answers the curiosity of whether starting treatment e.g. at birth would virtually eliminate morbidity, or whether it only slows the decline once it has started.

          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)?

          • By sleight42 2025-09-2414:30

            To me, as an HD widower, it would have meant that my dead wife would had lived until 2043 and had a decade more of a mostly normal life.

  • By tsoukase 2025-09-2420:053 reply

    Huntington's is among the best candidates for a genetic cure: well known gene and mechanism, definitive pre symptomatic diagnosis, slow progression.

    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.

    • By missedthecue 2025-09-2420:21

      The FDA has already agreed that data collected from this trial could be used to support a future BLA, and UniQure said this morning they're moving ahead with the BLA. In other words, uniQure likely will not need to run another trial before obtaining FDA approval for AMT-130.

    • By Spacecosmonaut 2025-09-258:48

      I'm a genetic engineer at a large pharma company. We corrected the HTT gene in patient derived iPSCs in the lab. The region is a long repeat sequence of which a section needs to be deleted. Because of this the locus is quite difficult to genetically engineer, since it is difficult to target just the diseased allele but not the wild-type allele.

      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.

    • By RataNova 2025-09-258:421 reply

      Huntington's should be low-hanging fruit for gene therapy, at least in theory: monogenic, fully penetrant, good biomarkers, and a long diagnostic runway

      • By omnibrain 2025-09-259:24

        I think one of the troubles is deliviring the therapy, because generally the brain is protected from virii reaching him.

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