Evidence map›Paper›PMID 41087673›Full record

ArticlePharmaceutical research2025

Exosome-Mediated Delivery of a PLD1 Modulator Overcomes Bioavailability Hurdles to Target Synaptopathy in Neurodegenerative Diseases.

Shaneilahi Budhwani, Sravan Gopalkrishna Shetty Sreenivasamurthy, Klarissa H Garza, Pilar Flores-Espinosa, Ramkumar Menon, Ananth Kumar Kammala, Balaji Krishnan

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pharmaceutical research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Exploring the PLD1-tau interaction in Frontotemporal Dementia.bioRxiv : the preprint server for biology · 2026
    Article
  2. Review
  3. 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

7 authors.

Shaneilahi BudhwaniGraduate School for Biomedical Sciences, University of Texas Medical Branch, Galveston, TX, USA.ORCID http://orcid.org/0009-0007-0161-0002
Sravan Gopalkrishna Shetty SreenivasamurthyGraduate School for Biomedical Sciences, University of Texas Medical Branch, Galveston, TX, USA.ORCID http://orcid.org/0000-0003-4427-8605
Klarissa H GarzaMitchell Center for Neurodegenerative Diseases, Department of Neurology, 301 University Blvd., The University of Texas Medical Branch at Galveston, Galveston, TX, 77555, USA.ORCID http://orcid.org/0009-0009-8206-9880
Pilar Flores-EspinosaDivision of Basic and Translational Research, Department of Obstetrics and Gynecology, 301 University Blvd., The University of Texas Medical Branch at Galveston, Galveston, TX, 77555, USA.ORCID http://orcid.org/0000-0003-2140-3629
Ramkumar MenonDivision of Basic and Translational Research, Department of Obstetrics and Gynecology, 301 University Blvd., The University of Texas Medical Branch at Galveston, Galveston, TX, 77555, USA.ORCID http://orcid.org/0000-0001-9213-6105
Ananth Kumar KammalaDivision of Basic and Translational Research, Department of Obstetrics and Gynecology, 301 University Blvd., The University of Texas Medical Branch at Galveston, Galveston, TX, 77555, USA. ankammal@utmb.edu.ORCID http://orcid.org/0000-0001-5300-2083
Balaji KrishnanMitchell Center for Neurodegenerative Diseases, Department of Neurology, 301 University Blvd., The University of Texas Medical Branch at Galveston, Galveston, TX, 77555, USA. bakrishn@utmb.edu.ORCID http://orcid.org/0000-0003-2074-4165

Funding

Phospholipase D1 Mediated Early Events Affecting Synaptic Dysfunction in Alzheimer's Disease and Related DementiaR01AG063945 · NIA · UNIVERSITY OF TEXAS MED BR GALVESTON · PI KRISHNAN, BALAJI · 2020 to 2024
$2.0M
Investigating the molecular mechanism of P-gp/NHERF-1 network at feto maternal interface and role of paracrine signaling of EVs containing drug transporter proteinsR01HD113193 · NICHD · UNIVERSITY OF TEXAS MED BR GALVESTON · PI KAMMALA, ANANTH KUMAR · 2023 to 2025
$914k
Synaptic PLD1 Levels/Signaling is Elevated Through Epigenetic Regulation in the CNS of AD Patients as a Function of Disease Severity and Cognitive DeclineR21AG059223 · NIA · UNIVERSITY OF TEXAS MED BR GALVESTON · PI KRISHNAN, BALAJI · 2018 to 2019
$434k
Alzheimer's Association AARG-17-533363NCATS NIH HHS R01HD113193-02NIA NIH HHS R01 AG063945NIA NIH HHS R01-AG063945NIA NIH HHS R21 AG059223NIA NIH HHS R21-AG059223NICHD NIH HHS R01 HD113193
6 · The paper itself

Abstract

introductionInhibition of Phospholipase D1 (PLD1) is a promising therapeutic strategy for Alzheimer's disease (AD) and related dementia (ADRD), yet clinical progress has been stalled by the inability of potent inhibitors to effectively cross the blood-brain barrier (BBB). While next-generation PLD1 inhibitors have failed in preclinical mammalian models due to poor CNS penetration, we revisit our functionally proven inhibitor VU0155069 (or VU01), demonstrating a definitive solution to this delivery challenge. METHODOLOGY: We engineered an exosome/extracellular vesicle (EVs)-based nanocarrier (Exo-VU01) to encapsulate VU0155069, optimizing drug payload via electroporation and confirming vesicle integrity through Nanoparticle Tracking Analysis. The therapeutic potential of this formulation was tested in a head-to-head intravenous pharmacokinetic study against free VU0155069 in mice.

resultsRelative to free VU0155069, which exhibited rapid systemic clearance and negligible brain retention, Exo-VU01 achieved approximately 20-fold higher brain area under the curve (AUC), underscoring its potential to optimize drug retention and regional biodistribution within the CNS.

conclusionOur study validates Exo-VU01 as a viable platform for CNS drug delivery. It provides increased efficacy for VU0155069 as a therapeutic candidate for AD/ADRD and establishes a clear translational pathway for targeted delivery.

Indexed as

ExosomesNeurodegenerative DiseasesPhospholipase DAnimalsBiological AvailabilityBlood-Brain BarrierBrainDrug CarriersDrug Delivery SystemsHumansMaleMiceNanoparticlesTissue DistributionDrug CarriersPhospholipase Dphospholipase D1Alzheimer’s disease and related dementia (AD/ADRD)exosomespharmacokineticsphospholipase D1 (PLD1)synaptopathytargeted drug deliveryVU0155069 (VU01)

Identifiers

PMID41087673
PMCPMC12768594

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Registered trials

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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.