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Record W3130363432 · doi:10.1038/s41467-021-21371-5

Lentivirus-mediated gene therapy for Fabry disease

2021· article· en· W3130363432 on OpenAlexafffund
Dwayne L. Barber, Ju Huang, C. Anthony Rupar, Jack W. Rip, Christiane Auray‐Blais, Michel Boutin, Pamela O’Hoski, Kristy Gargulak, William M. McKillop, Graeme Fraser, Syed Wasim, Kaye LeMoine, Shelly Jelinski, Ahsan Chaudhry, Nicole L. Prokopishyn, Chantal F. Morel, Stephen Couban, Peter Duggan, Daniel H. Fowler, Armand Keating, Michael L. West, Ronan Foley, Jeffrey A. Medin

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldMedicine
TopicLysosomal Storage Disorders Research
Canadian institutionsDalhousie UniversityFoothills Medical CentreAlberta Health ServicesNova Scotia Health AuthorityPrincess Margaret Cancer CentreUniversity of CalgaryHôpital FleurimontMcMaster UniversityAlberta Children's HospitalJuravinski HospitalWestern UniversityUniversity of TorontoUniversité de SherbrookeCentre Intégré Universitaire de Santé et de Services Sociaux du Centre-Sud-de-l'Île-de-MontréalUniversity Health NetworkChildren’s Health Research Institute
FundersCanadian Institutes of Health ResearchCumming School of Medicine, University of CalgaryKidney Foundation of CanadaGovernment of CanadaMidwest Athletes Against Childhood Cancer
KeywordsLentivirusFabry diseaseGenetic enhancementGeneDiseaseVirologyMedicineGeneticsBiologyHuman immunodeficiency virus (HIV)Viral diseaseInternal medicine

Abstract

fetched live from OpenAlex

Abstract Enzyme and chaperone therapies are used to treat Fabry disease. Such treatments are expensive and require intrusive biweekly infusions; they are also not particularly efficacious. In this pilot, single-arm study (NCT02800070), five adult males with Type 1 (classical) phenotype Fabry disease were infused with autologous lentivirus-transduced, CD34 + -selected, hematopoietic stem/progenitor cells engineered to express alpha-galactosidase A (α-gal A). Safety and toxicity are the primary endpoints. The non-myeloablative preparative regimen consisted of intravenous melphalan. No serious adverse events (AEs) are attributable to the investigational product. All patients produced α-gal A to near normal levels within one week. Vector is detected in peripheral blood and bone marrow cells, plasma and leukocytes demonstrate α-gal A activity within or above the reference range, and reductions in plasma and urine globotriaosylceramide (Gb 3 ) and globotriaosylsphingosine (lyso-Gb 3 ) are seen. While the study and evaluations are still ongoing, the first patient is nearly three years post-infusion. Three patients have elected to discontinue enzyme therapy.

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 imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

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.

Opus teacher head0.053
GPT teacher head0.380
Teacher spread0.327 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations118
Published2021
Admission routes2
Has abstractyes

Explore more

Same venueNature CommunicationsSame topicLysosomal Storage Disorders ResearchFrench-language works237,207