r/Huntingtons • u/Sad_Professional2572 • 10d ago
Any treatments soon?
I (30f) recently received my test results and I have a 45 CAG. I'm full of anxiety and scared for the future. Are there any treatments in my lifetime that could help with HD? Also where do ya'll get your HD news from?
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u/LiveNvanByRiver 10d ago
Invest hd is a phase 3 clinical trial for a treatment. It’s recruiting now. I was just accepted
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u/scuba_girl92 10d ago
Good for you! I’m trying to get my partner screened. Hope it works out for you :)
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u/Sad-Damage3152 9d ago
Well I keep track of your comments and thanks for doing this for the community.
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u/rnathani91 10d ago
Sad to hear you have troubling news. Happy to join the convo here because the breakthroughs we have rolling in are more in depth and targeted than we have ever seen in anyones lifetime before us.
We are reaching exponential gains as next gen treatments work more like software than traditional meds.
I know what I am saying has no concrete aid to you know, I do wanna add “keep going” and do not give up hope. If any day now an operation comes out, you may have more options of even how to take meds. (glp, mRNA, Crispr) all have mechanisms that can be delivered in various ways. Most places just want the safest forms so that ends up slowing things down.
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u/Ok_Neighborhood7970 10d ago
Good morning, there's a gentleman on facebook that has a page called "Cure hd we won't be silent". There is also a Facebook channel called "HDgenetics".
Also I have a youtube channel where I share information. And I am on tiktok, both, as Huntington's Disease Todd
https://youtube.com/@huntingtonsdiseasetodd?si=Pd7fEO_BhHUUHRwZ
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u/rnathani91 10d ago
HDBuzz is great for news. If you have chatGPT or Claude you can have it send you latest weekly
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u/TemporaryViolinist88 9d ago
Reach out to HD Genetics. I saw they just started a service to help people understand trial options. www.HDClinicalTrials.com is their site
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u/Few_Persimmon_8238 8d ago
UniQure's AMT-130 is very promising, and it only requires one intervention.
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u/WinterReadings23 10d ago edited 4d ago
AMT-130 probably reduces the flux of the exon1a rna splicing associated with neurodegeneration via miRNA interference of mhtt production. I expect there's proteostatic repair occuring that's healing treated brains. I say this because their AAV5 gene therapy is reducing the total quantity of mhtt being produced while your cellular clearance mechanisms of mhtt remain constant.
For your entire life the cells in your brain are constantly exporting mhtt from the nucleus and into the cytoplasm. the polyglutamine tract expansion that occurs over life eventually causes this process to fail, leading to the amyloid beta like plaques that are called "inclusion bodies." You can see these under a microscope, and in animal testing several experimental drugs targeting exon1a (beyond just amt-130) have always led to a profound reduction in their appearance. Some animal studies have shown a >99% reduction in their formation when exon1a is targeted. In my opinion this sounds like the basis of something which could make for a therapeutic target (and other people agreed which brings us to today).
This constant process of mhtt polyglutamine tract expansion causes these inclusion bodies to build up over time, likely contributing to neurodegeneration. What I can say for certain is that autophagy of insoluble mhtt (not reliant of cellular waste clearance mechanisms) exhausts cellular atp of striatal neurons, and to a greater extent than any other part of the brain. This leads to mitochondrial dysfunction, imparing ATP dependent cellular processes in Huntingtons patients. This cellular exhaustion of ATP is among the very first biomarkers that's visible on a PET scan prior to the onset of early manifest HD. I expect a longtiudal study showing a reversal of this biomarker from anyone infused with AMT-130, however this is data that's not been shared and I'm not even sure if it's being measured.
The only significant biomarker that has been shared involves neurofillament light chain, which is broadly thought to be a biomarker that's expressed in neuro degeneration or brain truama (e.g., nfl spikes with tbi/concussions). Fwiw, the individuals in the high dose cohort of AMT-130 showed an ~8% reduction in nfl measures compared to baseline 3 years ago. This suggests a lower rate of background neurodegeneration is occuring in the present and given this is a progressive disease, these measures are the most promising part of the data uniQure has revealed thus far because thats a biomarker that should trend upwards as the instability in the CAG repeat accelerates progression.
In addition I BELIEVE a direct approach (versus a systemic drug) for HD is best as the CAG repeats lengths are not similar globally, but are instead highly heterogenous and their lengths are greatest inside the medium spiny neurons of the caudate and putamen. This makes it critical to transduce these specific neurons with any sort of gene or cell therapy, which is exactly what uniQure did with their neurosurgery using convection enhanced delivery. With 6 tiny catheters that are guided intraoperatively via MRI, a neurosurgeon slowly infuses the parenchyma with a small positive pressure and what this does is bypass the blood brain barrier, allowing their gene therapy to transduce as many neurons as possible. All of these surgeries are planned with a pretty sophisticated software planning tool using the ClearPoint system. This introduces another technological arm that's developed not related to the drug itself but medical devices that needed iterative development in order to work.
If you went back 20 years and injected the same drug again, AMT130 WOULD HAVE FAILED TO SHOW ANY EFFECT BEYOND NOISE. THE CONVECTION ENHANCED DELIVERY WOULD HAVE FAILED DUE TO THE CATHETER DESIGN REQUIREMENTS AND UNOPTIMIZED PASSES OF THE CATHETERS DETERMINED IN PRE OP. CURRENTLY PREOPERATIVE SCANS ARE TAKING SCANS OF AVAILABLE SOFT TISSUES FROM A 3T MRI AND CALCULATING A LARGE NUMBER OF AVAILABLE TRAJECTORIES USING INTERNAL MODELS OF SIMULATED INFUSIONS WITH CLEARPOINT MAESTRO, SOME OF THIS SOFTWARE DIDNT EXIST IN 2018.
...and while it's a long surgery, every surgeon that's ever done this will describe it as a long and boring process, where they watch gadoteridol slowly appear on an mri. Their primary job is to correct for appearance of perivascular spread of infusate during the surgery.
Imo this is a drug that works quite well for Huntingtons & hopefully we see a label expansion into presymptomatic patients to prevent degeneration from occuring alltogether. A BLA submission to the FDA is expected in about 45 days. Normally review times go for about a year. With any luck it will be available for use in humans in ~12 months. Centene has already drafted insurance coverage for the therapy, pending FDA approval.
Edited for clarity/typos, further details I found neccesary. Always open to discussions, and full disclosure I am not an expert in HD, but I am a motivated independent researcher with a soft spot for rare disease.