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Antibody mediated targeting of autoimmune cells in multiple sclerosis

2020· article· en· W3016886375 on OpenAlexaffabout
Karin Rustad, Alexandra Ripplinger, Anastasye Kisheev, Josef Buttigieg

Bibliographic record

VenueThe FASEB Journal · 2020
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmunotherapy and Immune Responses
Canadian institutionsUniversity of Regina
Fundersnot available
KeywordsMyelin oligodendrocyte glycoproteinMultiple sclerosisExperimental autoimmune encephalomyelitisImmune systemAntigenMyelinImmunologyAntibodyOligodendrocyteApoptosisMedicineCancer researchCentral nervous systemBiologyNeuroscienceBiochemistry

Abstract

fetched live from OpenAlex

Multiple Sclerosis (MS) is a debilitating autoimmune disorder of the central nervous system (CNS) affecting over 77,000 Canadians, with a prevalence rate of almost one out of 300 Canadians, with the highest rates in Saskatchewan. Myelination of neuronal axons is essential for the normal and rapid electrical conduction along an axon. Currently there are few feasible options to treat MS. Here, we propose a novel therapy that specifically targets aberrant immune cells. We created a trimolecular peptide (TPC) that combines and antigen sequence (myelin oligodendrocyte glycoprotein; MOG 35‐55 ), a modified type IV secretatory system (TIVSS) peptide, and an apoptotic protein. As the TPC displays MOG, the TPC is hypothesized to only bind to immune cells that are actively seeking MOG (e.g. in MS). Since the TPC contains TIVSS, the cell that bound the antigen (e.g. MOG 35‐55 ) is forced to take up the TPC. Lastly, the apoptotic protein, which is now inside the cell, causes the cell to undergo apoptosis. Thus eliminating the aberrant cell. In order to test this TPC compound, we induced experimental autoimmune encephalopathy (EAE) using MOG 35‐55 . Test compound was administered 15 days post EAE induction. Administration of the TPC resulted in the suppression of autoimmune cells, as determined via flocytometry. We also found significant improvements in motor function as well as a reduction in MS plaque formation in the cerebellum. By targeting the pathogenic immune response whilst leaving the patient’s normal immune response intact, we believe this strategy will lead to improved clinical outcomes without the side effects seen in current MS therapies. Support or Funding Information Saskatchewan Health Research Foundation

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.029
GPT teacher head0.235
Teacher spread0.206 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2020
Admission routes2
Has abstractyes

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