Pharmacokinetics and Pharmacodynamics of Nomlabofusp in Non-clinical Studies of Friedreich’s Ataxia
Bibliographic record
Abstract
Nomlabofusp is a cell penetrant peptide-based recombinant fusion protein designed to enter cells and deliver human frataxin into the mitochondria of adults and children with Friedreich's ataxia. In this article we present non-clinical studies evaluating the pharmacology of nomlabofusp, including in a murine striated muscle tissue frataxin knockout model of Friedreich's ataxia. We demonstrate that subcutaneous administration of nomlabofusp distributes in a dose-dependent manner to several organs including the dorsal root ganglion, heart, and skeletal muscle, which are known to be predominantly affected in Friedreich's ataxia, as well as to other tissues, including skin. Plasma nomlabofusp concentrations correlated with levels of human frataxin delivered by nomlabofusp into tissues, and the increases in frataxin were correlated amongst tissues, especially with skin. In the knockout mice, we show that the pharmacokinetics and processing of nomlabofusp were comparable with wild type animals and that treatment with nomlabofusp halts the progression of cardiac dysfunction and significantly increased survival. Together, the findings from these non-clinical studies demonstrate that nomlabofusp exposure increases human frataxin in Friedreich's ataxia-relevant tissues and provide evidence of pharmacologic effects.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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 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".