Safety and Efficacy of First-in-Man Intrathecal Transplantation of Human Astrocytes (AstroRx) in ALS Patients: Phase I/IIa Clinical Trial Results
Bibliographic record
Abstract
Abstract Background: AstroRx is an allogeneic cell-based product, composed of healthy and functional human astrocytes derived from embryonic stem cells. We previously showed that AstroRx protects neurons in ALS animal models by multiple mechanisms, including clearance of toxic compounds (e.g. glutamate), reduction of oxidative stress, immunomodulation, and secretion of various neuroprotective factors. We hypothesized that transplantation of AstroRx can compensate for the malfunction of astrocytes in ALS patients in a clinical setting. Methods: We conducted a phase I/IIa, open-label, dose-escalating clinical trial to evaluate the safety, tolerability, and therapeutic effects of AstroRx transplantation in patients with ALS. Five patients were injected intrathecally with a single dose of 100x106 AstroRx cells and 5 patients with 250x106 cells (low and high dose, respectively). Safety and efficacy assessments were recorded during a period of 3-months pre-treatment (run-in) and 12-months post-treatment (follow-up). Results: A single administration of AstroRx at either low or high doses was safe and well tolerated. No adverse events (AEs) related to AstroRx cells were reported. Transient AEs related to the Intrathecal (IT) procedure were all mild to moderate and resolved. The study demonstrated a clinically meaningful effect that was maintained over the first 3 months after treatment, as measured by the pre-post slope change in ALSFRS-R. In the 100x106 AstroRx arm, the ALSFRS-R rate of deterioration was attenuated from -0.88/month pre-treatment to -0.30/month in the first 3 months post-treatment (p=0.039). In the 250x106 AstroRx arm, the ALSFRS-R slope from -1.43/mo to -0.78/mo (p=0.0023). The effect was even more profound in a rapid progressor subgroup of 5 patients. No significant difference in the rate of ALSFRS-R deterioration was observed beyond 3 months after treatment. No significant change was found in hand-held dynamometry (HHD), grip strength (JAMAR), ALSAQ-40, or serum biomarkers. Conclusions: Overall, these findings suggest that a single IT administration of AstroRx to ALS patients at a dose of 100x106 or 250x106 cells is safe. A signal of beneficial clinical effect was observed for the first 3 months post cell injection. These results support further investigation of repeated IT administrations of AstroRx. Trial Registration: NCT03482050
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".