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Record W4387077144 · doi:10.1002/adma.202304654

Brain‐Targeted Liposomes Loaded with Monoclonal Antibodies Reduce Alpha‐Synuclein Aggregation and Improve Behavioral Symptoms in Parkinson's Disease

2023· article· en· W4387077144 on OpenAlexfundno aff
Mor Sela, Maria Poley, Patricia Mora‐Raimundo, Shaked Kagan, Aviram Avital, Maya Kaduri, Gal Chen, Omer Adir, Adi Rozencweig, Yfat Weiss, Ofir Sade, Yael Leichtmann‐Bardoogo, Lilach Simchi, Shlomit Aga‐Mizrachi, Batia Bell, Yoel Yeretz‐Peretz, Aviv Zaid Or, Ashwani Choudhary, Idan Rosh, Diogo Cordeiro, Stav Cohen‐Adiv, Yevgeny Berdichevsky, Anas Odeh, Jeny Shklover, Janna Shainsky‐Roitman, Joshua E. Schroeder, Dov Hershkovitz, Peleg Hasson, Avraham Ashkenazi, Shani Stern, Tal Laviv, Ayal Ben‐Zvi, Avi Avital, Uri Ashery, Ben M. Maoz, Avi Schroeder

Bibliographic record

VenueAdvanced Materials · 2023
Typearticle
Languageen
FieldMedicine
TopicNeurological disorders and treatments
Canadian institutionsnot available
FundersNational Institute on AgingBen-Gurion University of the NegevEuropean CommissionTel Aviv UniversityRothschild Caesarea FoundationMichael J. Fox Foundation for Parkinson's ResearchPhospholipid Research CenterHebrew University of JerusalemIsrael National Institute for Health Policy ResearchAzrieli FoundationIsrael Science FoundationJewish National FundTeva Pharmaceutical Industries
KeywordsNeuroinflammationBlood–brain barrierMonoclonal antibodyNeurodegenerationTransferrinLiposomePharmacologyParkinson's diseaseIn vivoTransferrin receptorNeuroscienceMedicineChemistryAntibodyBiologyImmunologyDiseaseBiochemistryPathologyCentral nervous system

Abstract

fetched live from OpenAlex

Monoclonal antibodies (mAbs) hold promise in treating Parkinson's disease (PD), although poor delivery to the brain hinders their therapeutic application. In the current study, it is demonstrated that brain-targeted liposomes (BTL) enhance the delivery of mAbs across the blood-brain-barrier (BBB) and into neurons, thereby allowing the intracellular and extracellular treatment of the PD brain. BTL are decorated with transferrin to improve brain targeting through overexpressed transferrin-receptors on the BBB during PD. BTL are loaded with SynO4, a mAb that inhibits alpha-synuclein (AS) aggregation, a pathological hallmark of PD. It is shown that 100-nm BTL cross human BBB models intact and are taken up by primary neurons. Within neurons, SynO4 is released from the nanoparticles and bound to its target, thereby reducing AS aggregation, and enhancing neuronal viability. In vivo, intravenous BTL administration results in a sevenfold increase in mAbs in brain cells, decreasing AS aggregation and neuroinflammation. Treatment with BTL also improve behavioral motor function and learning ability in mice, with a favorable safety profile. Accordingly, targeted nanotechnologies offer a valuable platform for drug delivery to treat brain neurodegeneration.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.559
Threshold uncertainty score0.581

Codex and Gemma teacher scores by category

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 integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.015
GPT teacher head0.288
Teacher spread0.273 · 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 teacher head, 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

Citations83
Published2023
Admission routes1
Has abstractyes

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