241 Intrathecal antisense oligonucleotide delivery in HD: experience from RG6042 programme and best practice considerations
Bibliographic record
Abstract
Intrathecal administration involves the introduction of a drug substance into the subarachnoid space of the spinal column through a needle inserted into the lower back via lumbar puncture (LP) or via a special device. This procedure is used when drugs cannot cross the blood-brain barrier. Once injected, drugs are distributed within the cerebrospinal fluid from which they can access target tissues in spinal cord and brain. We use the intrathecal route to deliver RG6042 (previously HTTRx), an investigational, huntingtin mRNA- targeting antisense oligonucleotide to patients with Huntington’s disease (HD). Experience on intrathe- cal administration via LP has been gained in the RG6042 clinical development programme, including the double-blind, placebo-controlled, multiple ascending dose, Phase I/IIa study ( NCT02519036 ) in 46 patients with early manifest HD and an open-label extension ( NCT03342053 ) where patients received 120 mg RG6042 monthly or every other month in a 62-week treatment period (total procedures ≥400 in the programme to date). We will report on the experience with intrathecal drug delivery across these two studies and present information on suggested best practices in HD. Procedure-related videos will be shared, including use of spinal ultrasound. Finally, we will describe real-world considerations of implementing intrathecally delivered therapies in the clinical interface. alessia.nicotra@roche.com
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.005 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".