Evidence map›Paper›PMID 33964142›Full record

ArticleBrain : a journal of neurology2021

Pharmacological SARM1 inhibition protects axon structure and function in paclitaxel-induced peripheral neuropathy.

Todd Bosanac, Robert O Hughes, Thomas Engber, Rajesh Devraj, Andrew Brearley, Kerstin Danker, Kenneth Young, Jens Kopatz, Melanie Hermann, Antoine Berthemy and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Brain : a journal of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed, 1 pooled it
9.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

89 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Peripheral Neuropathy in Metabolic Stress.International journal of molecular sciences · 2026
    Review
  9. Review
  10. Article
  11. Targeting the SARM1-cADPR-CaArthritis research & therapy · 2026
    Article
  12. Review
  13. Article
  14. Article
  15. Caspase-3 cleaves and activates the NADase SARM1 to promote apoptosis, linking two cell death mechanisms.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  16. Article
  17. Article
  18. A metabolic cell death program downstream of SARM1 couples NADProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  19. Review
  20. Article

29 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 3 countries.

Todd BosanacDisarm Therapeutics, a wholly owned subsidiary of Eli Lilly & Co., Cambridge MA 02142, USA.
Robert O HughesDisarm Therapeutics, a wholly owned subsidiary of Eli Lilly & Co., Cambridge MA 02142, USA.
Thomas EngberDisarm Therapeutics, a wholly owned subsidiary of Eli Lilly & Co., Cambridge MA 02142, USA.
Rajesh DevrajDisarm Therapeutics, a wholly owned subsidiary of Eli Lilly & Co., Cambridge MA 02142, USA.
Andrew BrearleyEvotec (UK), Abingdon, Oxfordshire, OX14 4RZ, UK.ORCID 0000-0001-5490-2446
Kerstin DankerEvotec SE, 22419 Hamburg, Germany.
Kenneth YoungEvotec SE, 22419 Hamburg, Germany.
Jens KopatzEvotec SE, 22419 Hamburg, Germany.
Melanie HermannEvotec SE, 22419 Hamburg, Germany.
Antoine BerthemyEvotec France SAS, 31036 Toulouse, France.
Susan BoyceEvotec SE, 22419 Hamburg, Germany.
Jonathan BentleyEvotec (UK), Abingdon, Oxfordshire, OX14 4RZ, UK.
Raul KraussDisarm Therapeutics, a wholly owned subsidiary of Eli Lilly & Co., Cambridge MA 02142, USA.
Eli Lilly (United States) · USEvotec (Germany) · DEEvotec (United Kingdom) · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Axonal degeneration is an early and ongoing event that causes disability and disease progression in many neurodegenerative disorders of the peripheral and central nervous systems. Chemotherapy-induced peripheral neuropathy (CIPN) is a major cause of morbidity and the main cause of dose reductions and discontinuations in cancer treatment. Preclinical evidence indicates that activation of the Wallerian-like degeneration pathway driven by sterile alpha and TIR motif containing 1 (SARM1) is responsible for axonopathy in CIPN. SARM1 is the central driver of an evolutionarily conserved programme of axonal degeneration downstream of chemical, inflammatory, mechanical or metabolic insults to the axon. SARM1 contains an intrinsic NADase enzymatic activity essential for its pro-degenerative functions, making it a compelling therapeutic target to treat neurodegeneration characterized by axonopathies of the peripheral and central nervous systems. Small molecule SARM1 inhibitors have the potential to prevent axonal degeneration in peripheral and central axonopathies and to provide a transformational disease-modifying treatment for these disorders. Using a biochemical assay for SARM1 NADase we identified a novel series of potent and selective irreversible isothiazole inhibitors of SARM1 enzymatic activity that protected rodent and human axons in vitro. In sciatic nerve axotomy, we observed that these irreversible SARM1 inhibitors decreased a rise in nerve cADPR and plasma neurofilament light chain released from injured sciatic nerves in vivo. In a mouse paclitaxel model of CIPN we determined that Sarm1 knockout mice prevented loss of axonal function, assessed by sensory nerve action potential amplitudes of the tail nerve, in a gene-dosage-dependent manner. In that CIPN model, the irreversible SARM1 inhibitors prevented loss of intraepidermal nerve fibres induced by paclitaxel and provided partial protection of axonal function assessed by sensory nerve action potential amplitude and mechanical allodynia.

Indexed as

AnimalsAntineoplastic Agents, PhytogenicArmadillo Domain ProteinsAxonsCells, CulturedCytoskeletal ProteinsDose-Response Relationship, DrugHEK293 CellsHumansInduced Pluripotent Stem CellsMiceMice, KnockoutPaclitaxelPeripheral Nervous System DiseasesThiazolesAntineoplastic Agents, PhytogenicArmadillo Domain ProteinsCytoskeletal ProteinsPaclitaxelSARM1 protein, mouseThiazolesALSaxonal degenerationCIPNmultiple sclerosisneurodegeneration

Identifiers

PMID33964142
PMCPMC8634121
OpenAlexW3163504032

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.