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A welcoming home for HD research

Helping people make sense of Huntington's disease.

An open HD research hub for families, learners, and researchers. See what is changing, understand why it matters, and ask questions against the actual papers and trials.

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Latest HDBuzz + paper updates Trials 30 active, 18 recruiting Programs AMT-130, votoplam, SKY-0515

We are data scientists, not doctors. This is a research and education tool. For care decisions, please reach out to HDSA, HDBuzz, HDYO, or your own neurologist.

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Autonomous research agents
Refreshed today at 08:43 UTC · 20 papers · 30 trials · 20 targets
draft preprint_scout
Preprint scout indexed 63 HD preprints from biorxiv + medrxiv
today at 08:43 UTC
science experiment_runner
Experiment #011 published
today at 08:33 UTC
science experiment_runner
Experiment #010 published
today at 08:33 UTC
science experiment_runner
Experiment #008 published
today at 08:33 UTC
cloud_sync data_fetcher
Daily data refresh landed on main
0 days ago
biotech hypothesis_refiner
Hypothesis refiner reviewed 80 drug ideas
Jul 15
menu_book paper_scout
Paper scout ingested 76 papers
May 5
What the agents pulled this week
Daily refresh · runningEdge pipeline · runs weeklyExperiments shipped · 11Active hypotheses · 80
What we've learned

Eleven experiments. Honest writeups. Reproducible.

Each one asks one question, runs Gemma 4 or its predecessors over real PubMed papers, and ships the result, including what didn't work.

EXP-001 Mar 27, 2026

First-look LLM triage: 22 HD abstracts on Llama 3.1

Post-translational modifications of huntingtin (phosphorylation, SUMOylation, O-GlcNAcylation) are getting significant research attention as potential drug targets.

Model: llama3.1:8b Read the writeup arrow_forward
EXP-002 Mar 30, 2026

Full-text deep read: 16 HD papers on Llama 3.1

The K845N variant of LIG1 confers enhanced substrate discrimination and increased repair fidelity, suppressing somatic CAG expansion in mice.

Model: llama3.1:8b Read the writeup arrow_forward
EXP-003 Apr 02, 2026

Model comparison: qwen3.5 vs Llama 3.1 on the EXP-002 corpus

A model-comparison run: re-analyzed the Experiment #2 corpus with qwen3.5:27b. Writeup available with the raw results and reproducibility notes.

Model: qwen3.5:27b Read the writeup arrow_forward
EXP-003-GEMMA Apr 02, 2026

Gemma 4 finds what Llama missed: multi-mechanism HD pathology

Neurodegeneration is not attributable to a single mechanism but results from a complex, interacting pathogenic network involving protein misfolding/aggregation, mitochondrial dysfunction, neuroinflammation, metabolic dysregulation, and gut dysbiosis, necess...

Model: gemma4:latest Read on GitHub open_in_new
EXP-004 Apr 07, 2026

Somatic CAG expansion drug screen (75-paper sweep)

Screened 75 papers across MSH3, FAN1, PMS1, MLH1, LIG1, the MutSbeta to MutLgamma to LIG1 pathway now driving HD drug development at LoQus23, Harness, Skyhawk, and Rgenta.

Model: gemma4:latest Read the writeup arrow_forward
EXP-005 Apr 19, 2026

Expanded corpus: the two-track HD pathology model

"Two-Track" Pathology Model: HD is increasingly seen as a confluence of two distinct processes: Track 1 (primary genetic/structural damage to HTT) and Track 2 (secondary metabolic and immune failure).

Model: gemma4:latest Read on GitHub open_in_new
EXP-006 Jun 27, 2026

June 2026 fresh papers: mHTT hijacks neuronal lipid rafts

The role of lipid composition in regulating mutant huntingtin (mHTT) dimerization and its association with neuronal membranes is a highly quantitative and validated mechanism, suggesting membrane integrity/lipid metabolism as a primary therapeutic axis.

Model: gemma4:latest Read on GitHub open_in_new
EXP-007 Jun 27, 2026

The lipid-proteostasis cascade: what breaks first in HD?

The primary pathogenic event is hypothesized to be the disruption of cellular membrane microdomains by mutant huntingtin (mHTT), establishing a lipid $\rightarrow$ proteostasis failure cascade.

Model: gemma4:latest Read the writeup arrow_forward
EXP-008 Jun 29, 2026

Does HD's damage start in the epigenome, before symptoms?

Epigenetic dysregulation (TET1 suppression) is an early molecular event preceding clinical HD symptoms, establishing a viable pre-symptomatic intervention window.

Model: gemma4:latest Read the writeup arrow_forward
EXP-009 Jun 29, 2026

Does Huntington's start in the gut?

HD is fundamentally a systemic disorder requiring intervention at the gut barrier and metabolic level, not just the CNS (42181874).

Model: gemma4:latest Read the writeup arrow_forward
EXP-010 Jul 02, 2026

The NAD+ bottleneck: an energy crisis before symptoms

81 papers analyzed. Impaired DNA repair over-activates PARP1, which burns NAD+ and starves mitochondria. Nicotinamide Riboside scores 95/100 — and is already in a Phase 2 HD trial (NCT06853743).

Model: gemma4:latest Read the writeup arrow_forward
EXP-011 Jul 15, 2026

A footwear concept for chorea-related instability

An AI-assisted design study, not a device. A margin-of-stability model (Hof 2005) computes a flared outsole could raise the recoverable sudden-movement velocity ~83% (15 to 27 cm/s); a trade-off model finds a patient-specific optimal flare; and a grounded-moonshot map shows real partners (Adidas 4D/Carbon, New Balance, Enroll-HD/CHDI) who could build and test it. Falsifiable, disclaimed, unbuilt.

Model: design study Read the writeup arrow_forward
See all 13 drug hypotheses, scored arrow_forward
How the Hub works

Pick a topic. Read what it means. Then do something with it.

Huntingtin-lowering (ASOs and gene therapy)

A strategy worth watching A simple idea, big stakes

Picture the huntingtin protein as a faulty thermostat that someone left turned up too high. Huntingtin-lowering programs try to turn the dial back down, so the brain has less of the harmful version to deal with in the first place.

What it is

A family of treatments that tries to make the brain produce less of the huntingtin protein. Some are repeat injections, some are a one-time gene therapy.

Read this at:
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What the Hub is tracking today
20
Recent Papers
30
Active Trials
18
Recruiting Now
16+
Known Targets

Updated August 25, 2026 at 08:43 AM. Auto-refreshed daily from PubMed, ClinicalTrials.gov, HDBuzz, and Open Targets.

What's Happening Now

HD News + Breakthroughs

More on HDBuzz open_in_new
24 Aug 2026

Taking A Short Cut: New Routes to Huntingtin-Lowering Therapies
20 Aug 2026

A shot in the arm for HTT lowering: INSIGHTT trial begins testing SRP-1005
17 Aug 2026

The 2026 HDBuzz Prize for Young Science Writers Is Open!
14 Aug 2026

HD2026 Milton Wexler Biennial Symposium Day 3
13 Aug 2026

HD2026 Milton Wexler Biennial Symposium Day 2
Fresh from PubMed

Latest Research Papers

All HD papers open_in_new
2026 Aug — Journal of Huntington's disease
somatic expansionprotein structure

Altered myelin sphingolipid and glycerophospholipid profiles in Huntington disease.

Huntington's disease (HD) is a fatal neurodegenerative disease caused by a CAG repeat expansion in the Huntingtin gene (HTT). While classically considered a disease of grey matter, recent imaging data

PubMed open_in_new
2026 Aug — Molecular therapy : the journal of the A
gene therapyprotein structure

Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expansion of a CAG trinucleotide repeat in the huntingtin (HTT) gene, which leads to a mutant protein that destroys ne

PubMed open_in_new
2026 Jul — Nature biomedical engineering
gene therapysomatic expansionprotein structure

In vivo CRISPR base editing for treatment of Huntington's disease.

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat within exon 1 of the huntingtin (HTT) gene, resulting in a mutant protein that drives neuronal dysfunct

PubMed open_in_new
2026 Jul — Current pharmaceutical biotechnology
somatic expansionclinical trialprotein structure

Emerging Pharmacological Therapies for Huntington's Disease: Translational Insights from Recent Clin

Huntington's disease [HD] is a progressive, autosomal dominant neurodegenerative disorder caused by a pathogenic CAG repeat expansion in the HTT gene, resulting in mutant huntingtin [mHTT] protein acc

PubMed open_in_new
2026 Aug — Rejuvenation research
biomarkerprotein structure

Huntington's Disease: An Overview of Biomarkers in Prognostic, Diagnostic, and Therapeutic Managemen

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and psychiatric disturbances. It is caused by the abnormal expansion of cyt

PubMed open_in_new
2026 Aug — Science translational medicine
somatic expansionclinical trialprotein structure

Blocking somatic repeat expansion and lowering huntingtin by RNAi synergize to attenuate Huntington'

Huntington's disease (HD) is a progressive neurodegenerative disorder with no approved therapies. Despite multiple clinical trials, huntingtin (HTT)-lowering strategies have yet to show meaningful cli

PubMed open_in_new
Reasons for Optimism

Active Clinical Trials

30 trials, 57,291 patients enrolled, 18 recruiting now

ClinicalTrials.gov open_in_new
NCT ID Title Sponsor Phase Status Intervention
NCT07503743 Biology-Driven Cognitive Profiling in Huntington's Fundació Institut de Rece N/A Active Not Recruiting
NCT04478734 Trial of the Combined Use of Thiamine and Biotin i Fundación Pública Andaluz PHASE2 Recruiting Moderate doses of Thiamine y Biotin; Hig
NCT04713982 Impact of Deutetrabenazine on Functional Speech an Vanderbilt University Med PHASE2, PHASE3 Active Not Recruiting Deutetrabenazine
NCT05541627 A Study to Evaluate AB-1001 Striatal Administratio AskBio France, SAS, a sub PHASE1, PHASE2 Active Not Recruiting AB-1001 Gene Therapy
NCT06828471 Social Cognition Training in Individuals With Hunt Rush University Medical C NA Recruiting Social Cognition Training
NCT03434548 IMarkHD: in Vivo Longitudinal Imaging of HD Pathol King's College London N/A Recruiting PET imaging; Multi-modal MRI imaging
NCT07246941 A Study to Evaluate the Safety, Tolerability, Phar Hoffmann-La Roche PHASE1 Active Not Recruiting RG6496; Placebo
NCT06853743 The NAD-HD Study: A Study to Investigate Efficacy Oslo University Hospital PHASE2 Recruiting Nicotinamide Riboside (NR); Placebo
NCT05243017 Safety and Efficacy of AMT-130 in European Adults UniQure Biopharma B.V. PHASE1, PHASE2 Active Not Recruiting intra-striatal rAAV5-miHTT
NCT06254482 An Extension Study to Evaluate the Long-Term Safet Novartis Pharmaceuticals PHASE2 Active Not Recruiting Votoplam
Open Research

Published Research Ideas

AI-assisted repurposing ideas with explicit uncertainty. These are starting points for review, not recommendations or validated findings.

Read Experiment #1: Full Analysis arrow_forward
TET1 activators / DNMT inhibitors (ascorbate, decitabine) Exploring
Target: TET1 / DNA methylation / epigenetic gene silencing

New June 2026 knock-in pig study (PMID 42322611): mHTT disrupts TBP binding to the TET1 promoter, silencing TET1 transcription before symptom onset. TET1 converts 5mC to 5hmC (DNA demethylation); its loss causes aberrant

Latest score: 90/100 Support: 5 Concerns: 3 Updated: 2026-06-29
anle138b Exploring
Target: mHTT oligomers / lipid raft disruption

Oligomer inhibitor shown to ameliorate HD pathology in mouse and cellular models. Exp 6 signal: mHTT hijacks neuronal lipid rafts; anle138b stabilizes oligomer conformation before raft association. Preclinical confidence

Latest score: 90/100 Support: 2 Concerns: 0 Updated: 2026-06-27
CYP46A1 activators (efavirenz) Exploring
Target: CYP46A1 / cholesterol catabolism / lipid raft stabilization

Exp 7 identified CYP46A1 activation as the highest-confidence early intervention: restoring cholesterol catabolism may stabilize lipid raft microdomains disrupted by mHTT, preventing the downstream proteostasis cascade.

Latest score: 88/100 Support: 3 Concerns: 1 Updated: 2026-06-27
HTT1a-selective ASO/RNA therapy Exploring
Target: HTT1a transcript isoform / selective mHTT lowering

New June 2026 paper: selectively targeting HTT1a isoform provides superior molecular rescue vs. lowering canonical HTT. HTT1a is enriched in disease-vulnerable neurons. Isoform-selective lowering preserves full-length HT

Latest score: 85/100 Support: 3 Concerns: 2 Updated: 2026-06-27
PROTACs (Proteolysis Targeting Chimeras) for selective mHTT degradation Preclinical
Target: Mutant HTT protein / proteasome-ubiquitin system / selective protein degradation

HDBuzz Jun 25 2026: PROTACs act as molecular glue, recruiting E3 ubiquitin ligases to tag mutant huntingtin (mHTT) for proteasomal destruction while leaving wild-type HTT intact. Unlike ASOs/siRNA (which lower all HTT mR

Latest score: 83/100 Support: 5 Concerns: 4 Updated: 2026-06-29
Somatic CRISPR editing of Msh3 Exploring
Target: Msh3 / somatic CAG expansion / DNA mismatch repair

New June 2026 paper: somatic CRISPR knockout of Msh3 mitigates HD pathology in mice. Msh3 drives somatic CAG repeat expansion in neurons — without it, the repeat stays stable. This is a one-time intervention that targets

Latest score: 82/100 Support: 3 Concerns: 2 Updated: 2026-06-27

Important: These hypotheses are triage artifacts, not evidence of efficacy. They have not been clinically validated, experimentally confirmed, or expert-reviewed unless explicitly stated.

These cards are generated from data/hypotheses_tracker.json, not hand-picked homepage copy. Are you an HD researcher? We'd love your feedback. Review and discuss on GitHub

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Who This Is For

This is best viewed as open research infrastructure: a place where data scientists, AI engineers, bioinformaticians, and researchers can test whether agent workflows actually help with literature review, hypothesis triage, and research communication.

Data Scientists + AI/ML Engineers

Run our autonomous research agents. Fork the repo. Try different models. Add experiments. This is open-source infrastructure you can build on.

Researchers + Domain Experts

Review our AI-generated hypotheses. Spot what's promising and what's wrong. Your expertise is what turns computational ideas into real science. Join the discussion.

Students + Curious Builders

Want to learn how AI applies to drug discovery? Read our experiment reports — we show every step, what worked, and what didn't. No PhD required to follow along.

For patients and families: This is not a medical resource. For support, guidance, and verified medical information, please go to HDSA, HDBuzz, or HDYO. They have doctors and scientists reviewing every word. We don't.

Trusted Organizations

Resources for Patients, Families + Researchers

These organizations are the real experts. We link to them because they do essential work.

HDSA
Support + Advocacy

Huntington's Disease Society of America. Find local support groups, social workers, Centers of Excellence. The primary advocacy organization in the US.
HDBuzz
Research News in Plain Language

Scientists explain HD research in words everyone can understand. The best place to follow new developments without needing a PhD.
HDYO
Young People

Huntington's Disease Youth Organization. Resources specifically for young people affected by HD — teens, young adults, and young families.
Enroll-HD
Join Research

The world's largest observational study for HD families. Your data helps researchers understand HD and design better clinical trials.
European HD Network
International Research

EHDN coordinates HD research across Europe. Clinical trials, registries, and working groups advancing the science globally.
HD Reach
Rehab + Exercise

Evidence-based rehabilitation exercises designed for people with HD. Physical therapy, speech therapy, and occupational therapy resources.
Make a Difference

Ways to Get Involved

Whether you're a patient, family member, researcher, developer, or just someone who cares.

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Join a Clinical Trial

18 HD trials are actively recruiting right now. Your participation directly accelerates the path to treatment.

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Contribute to Open Source

Our research agent, literature scanner, and drug repurposing tools are all open source. Data scientists, ML engineers, and bioinformaticians welcome.

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Patient and family stories drive awareness and funding. Share your experience with HDSA or on social media to help others feel less alone.

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Research funding saves lives. HDSA and CHDI Foundation fund the science that makes breakthroughs like AMT-130 possible.

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Share Feedback or Ideas

Are you an HD researcher? See something interesting in our hypotheses? Spot an error? We want to hear from you — every correction makes this better.

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