Longitudinal biomarker evaluation in Fabry disease patients receiving lentivirus-mediated gene therapy
Bibliographic record
Abstract
Aim: In 2016, a team of Canadian researchers initiated the world’s first gene therapy clinical trial for Fabry disease. The study, aiming to determine the safety and toxicity of lentivirus α-galactosidase A transduced autologous CD34+ cells in adult males with Fabry disease (n = 5), was conducted at three Canadian centers. The objective of the present work was to evaluate a profile of Fabry disease-related biomarkers in five participants during a 5-year surveillance period, as part of the evaluation of this novel therapy. Methods: Sixteen globotriaosylceramide (Gb3) isoforms and eight globotriaosylsphingosine (lyso-Gb3) analogues were measured by LC-MS/MS in plasma and urine at numerous time points before and after gene therapy. Plasma and peripheral blood leukocyte α-galactosidase A activity were also measured. Results: Levels of urine and plasma lyso-Gb3 and analogues, and urine Gb3 were lower after gene therapy and while treated with enzyme replacement therapy (ERT) compared to baseline (before gene therapy) in participants treated with ERT only. Three participants chose to cease ERT treatment at some point after gene therapy. Two of these patients had lower levels of urine and plasma lyso-Gb3 and analogues compared to baseline, whereas one participant had higher levels of these biomarkers compared to baseline. An increase in urine Gb3 was observed when ERT treatment ceased after gene therapy (P < 0.05) in all three participants. Conclusion: The evaluation of this complete glycosphingolipid biomarker profile was useful in monitoring the biochemical response to gene therapy in this cohort of five patients with Fabry disease.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
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 teacher head, 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".