J005 An update on select-hd, which is evaluating an allele-selective mutant huntingtin lowering approach in Huntington’s disease
Bibliographic record
Abstract
SELECT-HD is a phase 1b/2a clinical trial evaluating the investigational antisense oligonucleotide WVE-003 in early manifest Huntington’s disease. WVE-003 is designed to target a single nucleotide polymorphism (SNP3) that is associated with the mutant huntingtin allele (mHTT), enabling allele-selective lowering of mHTT and relative sparing of wild-type HTT (wtHTT). In September 2022, data from the first 18 participants who were administered a single dose of WVE-003 (30 mg, n=4; 60 mg, n=4; 90 mg, n=4; placebo, n=6) were reported. Through September 20, WVE-003 (30, 60, 90 mg) appeared generally safe and well-tolerated, with no serious adverse events or discontinuations. Adverse events were balanced across active and placebo groups, and mild-to-moderate in intensity. For biomarker analyses, the 30 and 60 mg cohorts were pooled, as only these cohorts had reached day 85, and there was no apparent dose response. The mean reduction in CSF mHTT compared with placebo was 35% (22% compared with baseline). Measured CSF wtHTT protein appeared consistent with allele-selectivity. Increases in neurofilament light chain from baseline were observed in some participants, and there were no clinically meaningful elevations in CSF white blood cell counts or protein that would indicate inflammation in the CNS. These data provided early indications of target engagement and a favorable safety profile for WVE-003 and enabled SELECT-HD to be adapted to expand the single-dose cohorts and to initiate a multidose cohort (30 mg dosed every eight weeks, n=24). This presentation will provide updated biomarker and safety data for all ongoing cohorts.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.004 |
| Insufficient payload (model declined to judge) | 0.013 | 0.006 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".