CoChat
Sign Up
Cited by 181Parkinson's Disease Mechanisms and TreatmentsDeep Brain Stimulation and Movement DisordersPluripotent Stem Cells Research

The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index; 6 of the 22 sources its claims cite were checked for support.

Phase I trial of hES cell-derived dopaminergic neurons for Parkinson’s disease

Open access
Tabar, V., Sarva, H., Lozano, A. M., Fasano, A., Kalia, S. K., Yu, K. K. H., Brennan, C., Ma, Y., Peng, S., Eidelberg, D., Tomishima, M., Irion, S., Stemple, W., Abid, N., Lampron, A., Studer, L., Henchcliffe, C.·2025·Nature
DOI 10.1038/s41586-025-08845-yPMC PMC12095069
Open this paper in CoChat — free account

Abstract

Fluoro-DOPA positron emission tomography uptake increased, indicating graft survival. Secondary and exploratory clinical outcomes showed improvement or stability, including improvement in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III OFF scores by an average of 23 points in the high-dose cohort. There were no graft-induced dyskinesias. These data demonstrate safety and support future definitive clinical studies.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

In a first-in-human, open-label phase I trial, bilateral putaminal transplantation of the hES cell-derived dopaminergic neuron progenitor product bemdaneprocel met its 1-year safety and tolerability objectives in 12 patients with Parkinson’s disease. At 18 months, 18F-DOPA PET uptake increased in the putamen and MDS-UPDRS Part III OFF scores improved, especially in the high-dose cohort, with no graft-induced dyskinesias reported.

Key findings

  • Twelve patients were enrolled sequentially into low-dose (0.9 million cells per putamen, n = 5) and high-dose (2.7 million cells per putamen, n = 7) cohorts; all received 1 year of immunosuppression. The primary safety/tolerability criteria were satisfied at 12 months, with no adverse events related to the cell product and no deaths, tumours, abnormal tissue overgrowth or intracerebral haemorrhages detected by MRI.
  • At 18 months after transplantation, MDS-UPDRS Part III OFF scores decreased by a mean (s.d.) of 8.6 points (29.2) in the low-dose cohort and 23.0 points (7.9) in the high-dose cohort. Mean good ON times increased by 0.2 h (3.8 h) in the low-dose cohort and 2.7 h (1.6 h) in the high-dose cohort.
  • Putaminal 18F-DOPA PET uptake increased bilaterally across cohorts, supporting graft survival through 18 months, 6 months after immunosuppression discontinuation; caudate uptake was stable to decreased. There were no reports of graft-induced dyskinesias through 18 months.
  • Through 18 months, there were 78 cumulative treatment-emergent adverse events; most were mild or moderate, and none were related to bemdaneprocel. Two serious adverse events occurred at 12 months: one COVID-19 hospitalization and one seizure attributed to surgery; a later gastrointestinal haemorrhage at approximately 15 months was assessed as unrelated.

Methods

  • First-in-human, multisite, open-label phase I trial (NCT04802733) of cryopreserved, off-the-shelf bemdaneprocel derived from hES cells, grafted bilaterally into the post-commissural putamen via nine deposits per putamen in a single surgical session.
  • Participants had confirmed Parkinson’s disease; 12 were enrolled sequentially into low-dose then high-dose cohorts after a 30-day data safety monitoring committee pause. Median age was 67.0 years, 75% were male, and median time since diagnosis was 9 years.
  • Outcomes included safety/tolerability at 1 year, 18F-DOPA PET imaging at baseline, 12 and 18 months, MDS-UPDRS Part III OFF and adjusted PD diary good ON times, plus exploratory motor, non-motor and quality-of-life measures. Analyses were descriptive by cohort; no inferential statistical testing was performed because of the small number of participants.

Limitations

  • The paper states that the study was open-label, small, relatively short in observation, and not designed or powered to determine efficacy; expected PD symptom fluctuations and substantial placebo effects may influence results.
  • The paper states that PET data have limitations in resolution, signal-to-noise ratio and variability across and within patients and between dose cohorts, and that correlation between 18F-DOPA PET uptake and clinical performance can be variable. It also notes unknown kinetics of graft maturation and disease vulnerability, complicating dose-finding.
  • Evident from the design: there was no placebo or control arm and no blinding, and cohorts were enrolled sequentially rather than randomized, so efficacy signals cannot be attributed to the cell product alone.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/s41586-025-08845-y

Cites

51 of 51 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

6 of 22 cited sources checked · 2 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    The high dose targets the estimated number of healthy DA neurons in the intact substantia nigra (300,000).

    “The high dose targets the estimated number of healthy DA neurons in the intact substantia nigra35 (300,000 DA neurons), and the lower dose targets the estimated minimal number of surviving grafted DA neurons required for clinical benefit36 (100,000 DA neurons).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [35] Rudow, G. et al. Morphometry of the human substantia nigra in ageing and Parkinson’s disease. Acta Neuropathol. 115, 461–470 (2008). source

      The Discussion reports a mean of 305,000 pigmented neurons on one side of the substantia nigra in healthy older controls, close to the cited 300,000. It reports 424,000 in young controls, however, and the 305,000 figure counts pigmented neurons rather than specifically DA neurons. The unqualified estimate of 300,000 healthy DA neurons is therefore more general than this measurement supports. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
  • Interpretationcitation

    The absence of GID in this study through 18 months may relate to the lack of serotonergic neuron contaminants in bemdaneprocel.

    “The absence of GID in our study through 18 months is therefore particularly notable. This may relate to the lack of serotonergic neuron contaminants in bemdaneprocel, as preclinical studies confirmed the absence of serotonergic neurons in vitro and in vivo at 9 months after grafting34.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [34] Piao, J. et al. Preclinical efficacy and safety of a human embryonic stem cell-derived midbrain dopamine progenitor product, MSK-DA01. Cell Stem Cell 28, 217–229 (2021). source

      In Results and discussion, the Parkinsonian-rat graft analysis reports negative 5-HT staining, suggesting an absence of human serotonergic neurons in vivo. The cited paper does not establish their absence in vitro; its separate graft follow-up extends to day 266. The proposed link to the citing study’s absence of GID is the citing authors’ inference, not a finding attributed to this preclinical paper. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
  • Findingown data

    There were no graft-induced dyskinesias.

    “There were no graft-induced dyskinesias.”
    • Also stated in: § Safety and tolerability · plain
      “Notably, there were no reports of adverse events or clinical indications of graft-induced dyskinesias (GIDs) to date.”
    Quote in the paperSubstantial claim
  • Findingown data

    There were no deaths.

    “There were no deaths, no SAEs related to transplanted cells or immunosuppression, and there were no tumours, abnormal tissue overgrowth or intracerebral haemorrhages detected with MRI, which showed the expected postoperative changes (Extended Data Fig. 2).”
    Quote in the paperSubstantial claim
  • Findingown data

    Good ON times increased by 0.2 h (3.8 h) from baseline to 12.3 h (3.2 h) in the low-dose cohort.

    “The mean good ON times, based on adjusted PD diaries, increased by 0.2 h (3.8 h) from the baseline to 12.3 h (3.2 h) in the low-dose cohort and by 2.7 h (1.6 h) from the baseline to 13.6 h (1.9 h) in the high-dose cohort (Fig. 2c,d).”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim. 22
  • It may state two separate claims as one. 26

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Interpretationreasoning

    Allografting without long-term immunosuppression, coupled with cryopreservation, offers an off-the-shelf approach that could facilitate broader application of this therapy in the future.

    “the feasibility of allografting without long-term immunosuppression, coupled with cryopreservation, offers an off-the-shelf approach33,47 that could facilitate the broader application of this therapy in the future.”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [33] Kim, T. W. et al. Biphasic activation of WNT signaling facilitates the derivation of midbrain dopamine neurons from hESCs for translational use. Cell Stem Cell 28, 343–355 (2021). source

      The Results section on cryopreserved, off-the-shelf mDA cells reports high post-thaw viability, and the Discussion says the protocol should be suitable for a scalable product for human translation. But the graft experiments used immunocompromised rats; the paper does not establish that allografting is feasible without long-term immunosuppression. Page numbers were not available in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [47] Kirkeby, A. et al. Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson’s disease, STEM-PD. Cell Stem Cell 30, 1299–1314 (2023). source

      The Discussion says STEM-PD is an allogeneic therapy using a banked, cryopreserved product that makes clinical planning easier. But the trial design specifies immunotherapy for 12 months after grafting; the paper does not establish that grafts remain viable without immunosuppression thereafter or that broader application is feasible. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • It may state two separate claims as one.

    Premisecitation

    The 18F-DOPA PET SOR-1 method had been previously validated and used successfully in PET imaging studies of fetal cell transplantation.

    “This method had been previously validated49,50 and used successfully in the PET imaging studies of fetal cell transplantation25,42,51,52.”
    Quote in the paperNot a substantial claim2 of 6 sources checked
    • cites [49] Dhawan, V. et al. Comparative analysis of striatal FDOPA uptake in Parkinson’s disease: ratio method versus graphical approach. J. Nucl. Med. 43, 1324–1330 (2002).
    • cites [50] Jokinen, P. et al. Simple ratio analysis of 18F-fluorodopa uptake in striatal subregions separates patients with early Parkinson disease from healthy controls. J. Nucl. Med. 50, 893–899 (2009). source
    • cites [25] Olanow, C. W. et al. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann. Neurol. 54, 403–414 (2003). source
    • cites [42] Ma, Y. et al. Dopamine cell implantation in Parkinson’s disease: long-term clinical and 18F-FDOPA PET outcomes. J. Nucl. Med. 51, 7–15 (2010). source
    • cites [51] Nakamura, T. et al. Blinded positron emission tomography study of dopamine cell implantation for Parkinson’s disease. Ann. Neurol. 50, 181–187 (2001). source
    • cites [52] Ma, Y. et al. Dyskinesia after fetal cell transplantation for parkinsonism: a PET study. Ann. Neurol. 52, 628–634 (2002). source

  • It may state two separate claims as one.

    Findingown data

    Most TEAEs were mild or moderate in severity except for one fall that was deemed unrelated to treatment.

    “Most were mild or moderate in severity except for one fall that was deemed to be unrelated to treatment.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Findingown data

    NMSS scores varied across domains.

    “The NMSS scores varied across domains, with total scores trending towards stability in the high-dose cohort (Extended Data Table 9).”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Findingown data

    The trial achieved its primary safety and tolerability objectives and predefined safety criteria at 12 months after transplantation.

    “The trial achieved its primary objectives of safety and tolerability one year after transplantation, with no adverse events related to the cell product.”
    • Also stated in: § Safety and tolerability · plain
      “Predefined safety criteria for the primary outcome were satisfied at 12 months of follow-up after transplantation (Table 1).”
    • Also stated in: § Discussion · plain
      “bilateral putaminal transplantation of bemdaneprocel, a hES cell-derived DA neuron progenitor cell product, was generally well tolerated and achieved predefined safety criteria at 12 months as a primary end point.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    MRI imaging by 18 months did not show evidence of tumours or changes in the putaminal volume.

    “MRI imaging by 18 months did not show evidence of tumours or changes in the putaminal volume.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    There were no tumours, abnormal tissue overgrowth or intracerebral haemorrhages detected with MRI.

    “There were no deaths, no SAEs related to transplanted cells or immunosuppression, and there were no tumours, abnormal tissue overgrowth or intracerebral haemorrhages detected with MRI, which showed the expected postoperative changes (Extended Data Fig. 2).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    The clinical data show a greater amplitude of changes in UPDRS motor scores and reduction in OFF times, and an earlier onset of improvement, in the high-dose group.

    “The clinical data also show a greater amplitude of changes in UPDRS motor scores and reduction in OFF times, and an earlier onset of improvement, in the high-dose group.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingnone given

    Transplant feasibility was achieved, with intraoperative delivery of the total number of all intended cell deposits in all participants.

    “Transplant feasibility was achieved, with intraoperative delivery of the total number of all intended cell deposits in all of the participants.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    There were no SAEs related to transplanted cells or immunosuppression.

    “There were no deaths, no SAEs related to transplanted cells or immunosuppression, and there were no tumours, abnormal tissue overgrowth or intracerebral haemorrhages detected with MRI, which showed the expected postoperative changes (Extended Data Fig. 2).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    Aside from two severe TEAEs (one fall deemed unrelated to treatment and the SAE of gastrointestinal haemorrhage), all other TEAEs were mild or moderate in severity.

    “Aside from two severe TEAEs (one fall deemed unrelated to treatment and the aforementioned SAE of gastrointestinal haemorrhage), all others were mild or moderate in severity”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Findingown data

    Participants had a median age of 67.0 years (Q1, Q3: 64.5, 70.0); 67% were white and 75% were male.

    “The participants had a median age of 67.0 years (quartile 1 (Q1), Q3: 64.5, 70.0); 67% were white and 75% were male”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Findingown data

    Median time since diagnosis was 9.0 (Q1, Q3: 5.9, 11.5) years.

    “The median (Q1, Q3) time since diagnosis was 9.0 (5.9, 11.5) years.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Findingown data

    The most frequent TEAEs were in nervous system disorders (11 TEAEs in eight participants) and infections and infestations (10 TEAEs in seven participants).

    “TEAEs most frequently experienced by participants (Extended Data Table 6) were in the nervous system disorders (11 TEAEs in eight participants; Extended Data Table 7) and infections and infestations (10 TEAEs in seven participants; Extended Data Table 8) system/organ classes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Findingown data

    At baseline, all participants had a Hoehn-Yahr ON score of 2; 11 had an OFF score of 3 and one had an OFF score of 2.

    “At the baseline, all of the participants had a Hoehn–Yahr ON score of 2; 11 participants had a Hoehn–Yahr OFF score of 3 and one participant (low-dose cohort; Canada) had a score of 2.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Premisecitation

    Fetal grafting studies showed evidence of Lewy body formation within the graft; such disease transmission occurred only in later stages (more than a decade) after transplantation and affected only a minority of grafted DA neurons.

    “Fetal grafting studies showed evidence of Lewy body formation within the graft; however, such disease transmission occurred only in later stages (more than a decade) after transplantation and affected only a minority of grafted DA neurons43,44.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [43] Li, J. Y. et al. Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nat. Med. 14, 501–503 (2008). source
    • cites [44] Kordower, J. H., Chu, Y., Hauser, R. A., Freeman, T. B. & Olanow, C. W. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson’s disease. Nat. Med. 14, 504–506 (2008). source

  • It may state two separate claims as one.

    Premisecitation

    The MDS-UPDRS scale is the most widely used PD scale; it is well validated with high inter-rater reliability, and is sensitive to clinical changes.

    “This scale was selected as an outcome measure as it is the most widely used PD scale; it is well validated with high inter-rater reliability, and is sensitive to clinical changes40.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] Martinez–Martin, P., Rodriguez-Blazquez, C. & Forjaz, M. J. in Neuroscience and Biobehavioral Psychology 8–16 (Elsevier, 2017).

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Study design and conductnone given

    Enrolment occurred sequentially, first into the low-dose cohort, then into the high-dose cohort after a 30-day pause for evaluation by the data safety monitoring committee.

    “Enrolment occurred sequentially, first into the low-dose cohort, then into the high-dose cohort after a 30-day pause for evaluation by the data safety monitoring committee.”
    • Also stated in: § Study design and participants · plain
      “Enrolment occurred sequentially, first into the low-dose cohort, then into the high-dose cohort after a 30-day pause for evaluation by the data safety monitoring committee.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. It may state two separate claims as one.

    Study design and conductnone given

    18F-DOPA PET studies and analysis were performed at a single imaging site by investigators blinded to clinical and dose information.

    “18F-DOPA PET studies and analysis were performed at a single imaging site by investigators blinded to clinical and dose information.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim.

    Study design and conductreasoning

    The open-label study design, small patient cohort, relatively short observation period, expected fluctuations in PD symptoms and possibility of placebo effects warrant cautious interpretation of the efficacy data.

    “However, these data need to be interpreted cautiously in view of the open-label study design, the small patient cohort, the relatively short observation period, the expected fluctuations in PD symptoms and the possibility of placebo effects, which can be substantial in studies of PD.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Placebo effects can be substantial in studies of PD.
    • Rests on an assumption: PD symptoms fluctuate expectedly.

  • Probably not a substantial claim.

    Interpretationown data

    The paper's data support moving towards larger definitive clinical studies.

    “Taken together, our data support moving towards larger definitive clinical studies.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationown data

    Our results suggest that the dosing and duration of immunosuppression were sufficient, well-tolerated and protected cell survival and function.

    “Our results suggest that the dosing and duration of immunosuppression were sufficient, well-tolerated and protected cell survival and function; longer-term follow-up data will be critical to confirm these findings.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisenone given

    Consistently manufacturing and releasing an autologous product poses new challenges.

    “consistently manufacturing and releasing an autologous product poses new challenges”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductnone given

    All safety data from all participants were used to conduct the formal analysis of the primary end point at 1 year after transplantation.

    “All safety data from all of the participants were used to conduct the formal analysis of the primary end point at 1 year after transplantation.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Study design and conductnone given

    The phase I study was not designed nor powered for determining efficacy.

    “Although this phase I study is not designed nor powered for determining efficacy, there is nonetheless a possibility of improvement in the key secondary outcomes, including the MDS-UPDRS OFF motor scores, reflecting improved motor function without the benefit of anti-Parkinsonian medication.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Study design and conductown data

    The study was small and unblinded.

    “our findings should be interpreted carefully within the context of a small and unblinded safety and tolerability study”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Study design and conductnone given

    The cells were manufactured under cGMP conditions to establish working cell banks that were certified by Waisman Biomanufacturing.

    “The cells were manufactured under cGMP conditions to establish working cell banks that were further certified by Waisman Biomanufacturing.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. It may be too vague to check against evidence.

    Study design and conductnone given

    PET data should be interpreted cautiously owing to limitations in resolution, signal-to-noise ratio and variability across and within patients as well as between the low- and high-dose cohorts.

    “However, PET data should be interpreted cautiously owing to limitations in the resolution, signal-to-noise ratio and variability across and within patients as well as between the low- and high-dose cohorts.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The correlation between 18F-DOPA PET uptake and clinical performance can be variable.
    • Rests on an assumption: Graft survival alone is not sufficient to predict long-term patient benefit.

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Study design and conductown data

    Between 3 May 2021 and 30 March 2022, 17 participants were assessed for eligibility and five were excluded due to screening failure.

    “Between 3 May 2021 and 30 March 2022, 17 participants were assessed for eligibility; five were excluded due to screening failure.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductown data

    All participants signed the informed consent.

    “All of the participants signed the informed consent.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Study design and conductnone given

    The trial was conducted in accordance with the protocol and all applicable local government laws, regulations and guidance, including the Declaration of Helsinki and ICH requirements.

    “The trial was conducted in accordance with the protocol and all applicable local government laws, regulations and guidance, including policies with foundations in the World Medical Association Declaration of Helsinki, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductown data

    Inferential statistical testing was not performed due to the small number of participants.

    “Inferential statistical testing was not performed due to the small number of participants.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductown data

    The remaining 12 participants were sequentially enrolled into the low-dose (n = 5) or high-dose (n = 7) cohort.

    “The remaining 12 participants were sequentially enrolled into the low-dose (n = 5) or high-dose (n = 7) cohort”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductnone given

    A data safety monitoring committee and the institutional review boards monitored trial progression and data handling.

    “A data safety monitoring committee and the institutional review boards monitored trial progression and data handling.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Study design and conductown data

    The Tri-institutional Human Embryonic Stem Cell Research Oversight committee at MSKCC and WCM approved the study and the consent.

    “The Tri-institutional Human Embryonic Stem Cell Research Oversight committee (ESCRO) at MSKCC and WCM approved the study and the consent on 11 October 2019.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Study design and conductown data

    An institutional review board at Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine reviewed and approved the clinical protocol and the patient consent form.

    “An institutional review board at Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine reviewed and approved the clinical protocol (submitted with the Article) and the patient consent form.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Study design and conductown data

    At the time of the last participant completing the 18-month visit, median follow-up was 21.2 months (18.5, 24.7) and all participants were still engaged in clinical follow-up.

    “At the time of the last participant completing the 18-month visit, the median (min, max) follow-up time was 21.2 months (18.5, 24.7) and all of the participants were still engaged in clinical follow-up.”
    Quote in the paperNot a substantial claim
37 of 37

  • The paper relies on this without support.

    The correlation between 18F-DOPA PET uptake and clinical performance can be variable.

    “Furthermore, the correlation between 18F-DOPA PET uptake and clinical performance can be variable, and graft survival alone is not sufficient to predict long-term patient benefit.”

  • The paper relies on this without support.

    Graft survival alone is not sufficient to predict long-term patient benefit.

    “Furthermore, the correlation between 18F-DOPA PET uptake and clinical performance can be variable, and graft survival alone is not sufficient to predict long-term patient benefit.”

  • The paper relies on this without support.

    Placebo effects can be substantial in studies of PD.

    “the possibility of placebo effects, which can be substantial in studies of PD.”

  • The paper relies on this without support.

    PD symptoms fluctuate expectedly.

    “the expected fluctuations in PD symptoms”
4 of 4

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Conflicting counts of severe adverse events

    Minor

    The results describe only one adverse event outside the mild-or-moderate range, but the Methods identify two severe adverse events: a fall and gastrointestinal haemorrhage.

1 of 1

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Martinez–Martin, P., Rodriguez-Blazquez, C. & Forjaz, M. J. in Neuroscience and Biobehavioral Psychology 8–16 (Elsevier, 2017).

Cited by

Sorted by citations

Related

Metadata

Authors
Tabar, V., Sarva, H., Lozano, A. M., Fasano, A., Kalia, S. K., Yu, K. K. H., Brennan, C., Ma, Y., Peng, S., Eidelberg, D., Tomishima, M., Irion, S., Stemple, W., Abid, N., Lampron, A., Studer, L., & Henchcliffe, C.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • Weill Cornell Medicine (US)
  • University of Toronto (CA)
  • University Health Network (CA)
  • Feinstein Institute for Medical Research (US)
  • University of California, Irvine (US)
Corresponding author
Tabar, V.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2025-04-16
Volume
641
Issue
8064
Pages
978-983
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-025-08845-y
PMC
PMC12095069
OpenAlex
W4409502153
Cited by
181
References
51
Citations by year
2026: 124 · 2025: 57
FWCI
97.18
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Cancer Institute (P30CA008748)
  • National Institute of Neurological Disorders and Stroke (R01NS118067)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords
Parkinson's disease, human embryonic stem cells, dopaminergic neurons, cell therapy, graft survival, dyskinesia, safety
MeSH terms
Human Embryonic Stem Cells, Adult, Aged, Female, Graft Survival, Humans, Male, Middle Aged, Parkinson Disease, Putamen, Cohort Studies, Cryopreservation, Treatment Outcome, Stem Cell Transplantation, Positron-Emission Tomography, Dopaminergic Neurons

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

A language model drew the claims from the paper on 2026-11-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-11-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Cited sources are checked with a language model’s help (gpt-6-sol).

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review