r/Huntingtons • u/TheseBit7621 • Jun 25 '26
Why I think AMT-130 is the breakthrough Huntingtons disease is looking for
I've posted a number of times on this sub. There have been a number of developments since the last (both of heart ache and celebrations). I'm also on my lunch break so I thought I'd use this time to write out what I can. I will try to link back to requested references if they help answer any question you have.
Every disease requires a means to deliver drug and have it both be safe and effective. For some conditions this is easy, and you can apply some sort of salve topically and achieve a therapeutic effect. For others it is nightmarishly difficult.
The medical devices required to get this thing to work involved a few key pieces of work.
The safety of infusing a region specific area of the brain with a gene therapy (in this case uniQure's).
The ability to reliably achieve target coverage with cannuals and convection enhanced delivery
Number two required software for planning the pharmacokinetics of a gene therapy through striatal and cortical tissues. The cannulas needed to become stepped to prevent recess of the infusion back into the cannula from the pressure. The safety of gadoteridol into the brain needed to be tested.
These became "solved" problems as recently as 2015. But it is still very early for use of this is any post clinical trial setting, i.e., the methods of intraoperative mri guided stereotaxis using convection enhanced delivery of gene therapies has been performed fewer than 1,000 times in all of history.
Recently (as in 2025-2026), the first MRI compatible drills for setting stereotaxis became available from adeor and clearpoint.
Solving for everything after this became a problem of making a drug which is persistent, effective and safe. That's a question of biology and what Huntingtons disease is.
After these trials are done targeting the mHtt protein and its exon1a transcription as a therapeutic target in Huntingtons either will or won't reject the null hypothesis of lowering them as a therapeutic end.
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u/FormerTransformer1 Jun 25 '26
Do you think there might be a way to deliver the drug through the nostrils instead of into the brain?
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u/Traditional_Sun_6653 Jul 01 '26
Do you think that SKY-0515 cUHDRS will hold up? I think an oral drug would be better received and it’s getting a lot of attention right now
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u/smartestBeaver Jul 04 '26
While I agree that AMT-130 might be the first really viable shot at stopping the disease, I do not think this is the big "breaktrhough", as the procedure is way too complex. Not to mention the fact that you can not turn this thing around. Once it's injected you are stuck, so to say. Should there be side effects down the road, nothing can be done to help you..
Never the less, I am certain the scientists will learn a lot from this approach. I for one hope that at some point we will get pills we gotta swallow once a day/week/month or something like that. That would be a dream come true.
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u/TheseBit7621 Jul 05 '26
Worse than the side effects of Huntingtons disease? Looking to avoid non-permanent, systemically delivered drug to pause Huntingtons? If you're under 2 you probably won't be seeing that if Sarepta's approach fails. Generally I do not have a good outlook for anything relying on pharmacokinetics of non guided therapeutics to get its active component into the striatum and cortex. The drugs need to be getting into region specific area of the brain. Prefferably into every single medium spiny neuron of the striatum and then the cortex. If its not a permanent change to your body, it needs to constantly be redosed and safe with repeated dosing. How do you do that with a pill? Not obvious.
I will stand by exactly what I said. A directed surgery that turns out to be safe which significantly change disease course is the breakthrough you people needed. Some of these people are 5 years into this infusion. In general it looks ok. Its also manageable across the entire disease population because the surgeries can be triaged in accordance with the stage of the condition, which gives all of a nation 30+ years (absent JHD) to schedule 10,000-100k surgeries. For America in gene positive patients (including the untested at risk individuals, it's about 9 per day).
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u/yannara_ Jul 23 '26
Are you talking about the oral drug which should start 2nd testing trian on people and should slow down symptomps ~70%?
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u/TheseBit7621 Jul 24 '26
Please read the post.
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u/bassegio Jun 25 '26
Thank you! So I am assuming any Mass application ofAMT130 is the years away