Evidence map›Paper›PMID 37438842›Full record

ArticleActa neuropathologica communications2023

Bruton's tyrosine kinase inhibition reduces disease severity in a model of secondary progressive autoimmune demyelination.

Kirsten Scarlett Evonuk, Sen Wang, Josh Mattie, C J Cracchiolo, Reine Mager, Željko Ferenčić, Ethan Sprague, Brandon Carrier, Kai Schofield, Evelyn Martinez and 9 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

12 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Review
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

19 authors at 2 institutions in 1 country.

Kirsten Scarlett EvonukHooke Laboratories, LLC, 439 South Union Street, Lawrence, MA, 01843, USA. k.evonuk@hookelabs.com.ORCID 0000-0002-2750-0289
Sen WangHooke Laboratories, LLC, 439 South Union Street, Lawrence, MA, 01843, USA.
Josh MattieHooke Laboratories, LLC, 439 South Union Street, Lawrence, MA, 01843, USA.
C J CracchioloHooke Laboratories, LLC, 439 South Union Street, Lawrence, MA, 01843, USA.
Reine MagerHooke Laboratories, LLC, 439 South Union Street, Lawrence, MA, 01843, USA.
Željko FerenčićHooke Laboratories, LLC, 439 South Union Street, Lawrence, MA, 01843, USA.
Ethan SpragueHooke Laboratories, LLC, 439 South Union Street, Lawrence, MA, 01843, USA.
Brandon CarrierHooke Laboratories, LLC, 439 South Union Street, Lawrence, MA, 01843, USA.
Kai SchofieldHooke Laboratories, LLC, 439 South Union Street, Lawrence, MA, 01843, USA.
Evelyn MartinezHooke Laboratories, LLC, 439 South Union Street, Lawrence, MA, 01843, USA.
Zachary StewartHooke Laboratories, LLC, 439 South Union Street, Lawrence, MA, 01843, USA.
Tara PetrosinoHooke Laboratories, LLC, 439 South Union Street, Lawrence, MA, 01843, USA.
Gregory Andrew JohnsonHooke Laboratories, LLC, 439 South Union Street, Lawrence, MA, 01843, USA.
Isharat YusufGossamer Bio, 3013 Science Park Road, Suite 200, San Diego, CA, 92121, USA.
Warren PlaistedGossamer Bio, 3013 Science Park Road, Suite 200, San Diego, CA, 92121, USA.
Zachary NaimanGossamer Bio, 3013 Science Park Road, Suite 200, San Diego, CA, 92121, USA.
Timothy DelpHooke Laboratories, LLC, 439 South Union Street, Lawrence, MA, 01843, USA.
Laura CarterGossamer Bio, 3013 Science Park Road, Suite 200, San Diego, CA, 92121, USA.
Suzana MarušićHooke Laboratories, LLC, 439 South Union Street, Lawrence, MA, 01843, USA. s.marusic@hookelabs.com.
Gossamer Bio (United States) · USUnion University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bruton's tyrosine kinase (BTK) is an emerging target in multiple sclerosis (MS). Alongside its role in B cell receptor signaling and B cell development, BTK regulates myeloid cell activation and inflammatory responses. Here we demonstrate efficacy of BTK inhibition in a model of secondary progressive autoimmune demyelination in Biozzi mice with experimental autoimmune encephalomyelitis (EAE). We show that late in the course of disease, EAE severity could not be reduced with a potent relapse inhibitor, FTY720 (fingolimod), indicating that disease was relapse-independent. During this same phase of disease, treatment with a BTK inhibitor reduced both EAE severity and demyelination compared to vehicle treatment. Compared to vehicle treatment, late therapeutic BTK inhibition resulted in fewer spinal cord-infiltrating myeloid cells, with lower expression of CD86, pro-IL-1β, CD206, and Iba1, and higher expression of Arg1, in both tissue-resident and infiltrating myeloid cells, suggesting a less inflammatory myeloid cell milieu. These changes were accompanied by decreased spinal cord axonal damage. We show similar efficacy with two small molecule inhibitors, including a novel, highly selective, central nervous system-penetrant BTK inhibitor, GB7208. These results suggest that through lymphoid and myeloid cell regulation, BTK inhibition reduced neurodegeneration and disease progression during secondary progressive EAE.

Indexed as

Encephalomyelitis, Autoimmune, ExperimentalAgammaglobulinaemia Tyrosine KinaseAnimalsFingolimod HydrochlorideMiceMice, BiozziMyeloid CellsAgammaglobulinaemia Tyrosine KinaseFingolimod HydrochlorideB cellsDemyelinationExperimental autoimmune encephalomyelitisMicrogliaMultiple sclerosisMyeloid cellsSecondary progressive

Identifiers

PMID37438842
PMCPMC10337138
OpenAlexW4384067942

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.