Abstracts of the 16 <sup>th</sup> UK Neuromuscular Translational Research Conference, 29 <sup>th</sup> and 30 <sup>th</sup> March 2023
Bibliographic record
Abstract
Limb-girdle muscular dystrophy type R1 (LGMDR1 or LGMD2A) is a neuromuscular disorder caused by mutations in the calpain 3 gene (CAPN3).It affects predominantly the proximal skeletal muscles, leading to progressive weakness and atrophy and consequently loss of motor function.We aim at developing a therapeutic product based on gene transfer mediated by a vector derived from the adeno-associated virus (AAV).As some mutations in the calpain 3 gene have recently been observed to manifest as a dominant form of calpainopathy, we wanted to defi ne whether these mutations corresponded to haploinsuffi ciency or gain of function.The study of these particular mutations demonstrated that the fi rst mechanism was correct, indicating that these forms would also benefi t from gene replacement as for the recessive forms, de facto extending the indications for our gene therapy in development.To ensure the highest effi cacy and safety possible of the gene transfer, we engineered an AAV vector that present a high tropism for the skeletal muscle and that will express calpain 3 only in this tissue.We developed a new capsid through rational design with enhanced properties compared to the parental serotype.In particular, we demonstrated in vivo in mice using a GFP-luciferase transgene that it displayed a decreased tropism for the liver and an increased tropism for the skeletal muscles.In addition we showed a 10-fold increase in infection of human primary and IPs-derived differentiated myogenic cells compared to AAV9 and 8.We demonstrated the potential of transfer of the calpain3 gene using this newly devel- S01The MRC Nucleic Acid Therapy Accelerator (NATA) -its role in the translational research panorama in the UK
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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.408 | 0.242 |
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".