ArticleCell2023
PIKFYVE inhibition mitigates disease in models of diverse forms of ALS.
Erratum issued 2 registry-linked trialsAbstract read
In one paragraph
Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 66 papers.
0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
–field-weighted citation impact
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.
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.
A Phase 1b, Open-Label, Multiple Ascending Dose, Multicenter Study of VRG50635 in Participants With Sporadic and Familial Amyotrophic Lateral Sclerosis Followed by Long-Term Treatment
A Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of VRG50635 in Healthy Volunteers
Who cites it
66 citing papers in PubMed.
- Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB): A Translational Pharmacodynamic Biomarker for PIKfyve Inhibition With VRG50635.Clinical and translational science · 2026Trial
- Synthesis and evaluation of 3,5-disubstituted isothiazolo[4,5-b]pyridines, pyrazolo[4,3-b]pyridines and isothiazolo[3,4-b]pyrazines as inhibitors of PIKfyve.Bioorganic chemistry · 2026Article
- Targeting TDP-43 in sporadic amyotrophic lateral sclerosis.Journal of neurology · 2026Review
- Review
- Reducing PI4KIIIα Levels or Activity Limits Tau Seed Internalization and Assembly in Human Cortical Neurons.Cells · 2026Article
- Target identification and assessment in the era of AI.Nature reviews. Drug discovery · 2026Review
- MYC-driven gliosis impairs neuron-glia communication in amyotrophic lateral sclerosis.Brain : a journal of neurology · 2026Article
- Predictive Cellular Signatures from Live Human Motor Neurons Distinguish TDP-43 ALS and Enable ALS Subtype Stratification.bioRxiv : the preprint server for biology · 2026Article
- Article
- Article
- LAMP1 and LAMP2A localise to axonal organelles with distinct motility dynamics and partially overlapping molecular signatures in human neurons.Journal of cell science · 2026Article
- PIKfyve mediates the maturation of mycobacteria-containing vesicles.Frontiers in cellular and infection microbiology · 2026Article
- Autophagy: mechanisms, roles in human diseases, and therapeutic perspectives.Frontiers in cell and developmental biology · 2026Review
- Large-scale drug screening in iPSC-derived motor neurons from sporadic ALS patients identifies a potential combinatorial therapy.Nature neuroscience · 2026Article
- Breast Cancer-Secreted DPP3 Promotes Lung Metastasis by Remodelling the Vascular Niche in Lung via the Rap1 Signalling Pathway.Journal of extracellular vesicles · 2025Article
- Patient-derived induced pluripotent stem cells with a C9orf72 expansion as a model to study frontotemporal dementia pathologies.Molecular biology of the cell · 2025Article
- Disruption of the PIKfyve complex unveils an adaptive mechanism to promote lysosomal repair and mitochondrial homeostasis.Nature communications · 2025Article
- Isoginkgetin antagonizes ALS pathologies in its animal and patient iPSC models via PINK1-Parkin-dependent mitophagy.EMBO molecular medicine · 2025Article
- Physiological roles of phosphoinositides and inositol phosphates: Implications for metabolic dysfunction-associated steatotic liver disease.Clinical science (London, England : 1979) · 2025Review
- Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
28 authors.
Shu-Ting HungDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA 90033, USA; Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
Gabriel R LinaresDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA 90033, USA; Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
Wen-Hsuan ChangAcuraStem Incorporated, Monrovia, CA 91016, USA.
Yunsun EohDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA 90033, USA; Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
Gopinath KrishnanDepartment of Neurology, UMass Chan Medical School, Worcester, MA 01605, USA.
Stacee MendoncaAcuraStem Incorporated, Monrovia, CA 91016, USA.
Sarah HongAcuraStem Incorporated, Monrovia, CA 91016, USA.
Yingxiao ShiDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA 90033, USA; Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
Manuel SantanaDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA 90033, USA; Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
Chuol KuethDepartment of Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, PA 17033, USA.
Samantha Macklin-IsquierdoDepartment of Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, PA 17033, USA.
Sarah PerryDepartment of Neurobiology, University of Southern California, Los Angeles, CA 90089, USA.
Sarah DuhaimeCentre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Département de Pathologie et Biologie Cellulaire, Université de Montréal, Montréal, QC, Canada.
Claudia MaiosCentre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Département de Pathologie et Biologie Cellulaire, Université de Montréal, Montréal, QC, Canada.
Jonathan ChangDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA 90033, USA; Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
Joscany PerezDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA 90033, USA; Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
Alexander CoutoDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA 90033, USA; Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
Jesse LaiDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA 90033, USA; Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
Yichen LiDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA 90033, USA; Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
Samuel V AlworthAcuraStem Incorporated, Monrovia, CA 91016, USA.
Eric HendricksDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA 90033, USA; Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
Yaoming WangZilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA; Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Berislav V ZlokovicZilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA; Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Dion K DickmanDepartment of Neurobiology, University of Southern California, Los Angeles, CA 90089, USA.
J Alex ParkerCentre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Département de Pathologie et Biologie Cellulaire, Université de Montréal, Montréal, QC, Canada.
Daniela C ZarnescuDepartment of Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, PA 17033, USA.
Fen-Biao GaoDepartment of Neurology, UMass Chan Medical School, Worcester, MA 01605, USA.
Justin K IchidaDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, Los Angeles, CA 90033, USA; Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA. Electronic address: ichida@usc.edu.
Funding
USCADRC Diversity Supplement PachicanoP30AG066530 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HELENA Chang CHUI, ARTHUR W TOGA · 2020 to 2026
$27.8MUW Center for Mendelian GenomicsUM1HG006493 · NHGRI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, LEAL, SUZANNE M · 2016 to 2020
$15.3MValidating Secretory Autophagy as a Therapeutic Strategy for Diverse Forms of ALS and FTDR01NS097850 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ICHIDA, JUSTIN KAWIKA · 2016 to 2024
$5.5MLeveraging Natural Phenotypic Variations of Heterogenous ALS Populations-in-a-Dish to Enable Scalable Drug DiscoveryR01NS131409 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GOODARZI, HANI, ICHIDA, JUSTIN KAWIKA · 2022 to 2025
$4.9MNHGRI Genome Sequencing Program Coordinating CenterU24HG008956 · NHGRI · RUTGERS, THE STATE UNIV OF N.J. · PI BUYSKE, STEVEN G, MATISE, TARA C. · 2016 to 2020
$4.9MInvestigating Pathogenic Mechanisms of Frontotemporal Dementia Caused by Mutations in CHMP2B and TBK1R37NS057553 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI GAO, FEN-BIAO · 2018 to 2024
$4.3MMolecular Mechanisms Governing the Homeostatic Control of Synaptic StrengthR01NS091546 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI DICKMAN, DION KAI · 2015 to 2024
$4.3MUnderstanding Frontotemporal Dementia Using Drosophila and iPSC ModelsR01NS101986 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Fen-Biao Gao · 2017 to 2026
$3.6MTranslation dysregulation in neurodegenerationR01NS091299 · NINDS · UNIVERSITY OF ARIZONA · PI DANIELA C ZARNESCU · 2015 to 2026
$3.4MKinetic Phenotype Discovery Informatics for Neurological DiseasesR44NS097094 · NINDS · SVISION, LLC. · PI LEE, SHIH-JONG J · 2016 to 2019
$3.0MLineage reprogramming for hearing loss: development of drug screening and gene therapy approachesR01DC015530 · NIDCD · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ICHIDA, JUSTIN KAWIKA, MCMAHON, ANDREW P. · 2016 to 2020
$3.0MSynaptic Control of Glutamate HomeostasisR01NS111414 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI DICKMAN, DION KAI · 2019 to 2023
$1.8MNHGRI NIH HHS U24 HG008956NHGRI NIH HHS UM1 HG006493NIA NIH HHS P30 AG066530NIDCD NIH HHS R01 DC015530NIH HHS S10 OD021553NINDS NIH HHS R00 NS077435NINDS NIH HHS R01 NS091299NINDS NIH HHS R01 NS091546NINDS NIH HHS R01 NS097850NINDS NIH HHS R01 NS101986NINDS NIH HHS R01 NS111414NINDS NIH HHS R01 NS131409NINDS NIH HHS R37 NS057553NINDS NIH HHS R44 NS097094
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that results from many diverse genetic causes. Although therapeutics specifically targeting known causal mutations may rescue individual types of ALS, these approaches cannot treat most cases since they have unknown genetic etiology. Thus, there is a pressing need for therapeutic strategies that rescue multiple forms of ALS. Here, we show that pharmacological inhibition of PIKFYVE kinase activates an unconventional protein clearance mechanism involving exocytosis of aggregation-prone proteins. Reducing PIKFYVE activity ameliorates ALS pathology and extends survival of animal models and patient-derived motor neurons representing diverse forms of ALS including C9ORF72, TARDBP, FUS, and sporadic. These findings highlight a potential approach for mitigating ALS pathogenesis that does not require stimulating macroautophagy or the ubiquitin-proteosome system.
Indexed as
Amyotrophic Lateral SclerosisPhosphatidylinositol 3-KinasesAnimalsDisease Models, AnimalMotor NeuronsMutationRNA-Binding Protein FUSPhosphatidylinositol 3-KinasesRNA-Binding Protein FUSALSneurodegenerationPIKFYVE
Identifiers
What OpenQuestion holds
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LicenceTDM
Read underepoch 390
Registered trials
NCT06215755ClinicalTrials.gov
NCT06286475ClinicalTrials.gov
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.