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    GENE:

    GRN (Granulin Precursor)

    i
    Other names: GRN, Granulin Precursor, PCDGF, PGRN, Progranulin, CLN11, PC Cell-Derived Growth Factor, Glycoprotein Of 88 Kda, Glycoprotein 88, Proepithelin, Acrogranin, GP88, PEPI, Epithelin Precursor, Granulin-Epithelin, Epithelin, Granulins, GEP
    Associations

    News

    Trials
    24d
    Granulin+ Macrophages Promote Lineage Plasticity in Prostate Cancer Through Paracrine Signaling Loops. (PubMed, Genomics Proteomics Bioinformatics)
    Functional validation demonstrated GRN's critical role in driving epithelial-mesenchymal transition in vitro and conferring resistance to enzalutamide (ENZ) in patient-derived organoids...Furthermore, we identified three novel stromal populations [decorin (DCN)+ endothelial cells, C-C motif chemokine ligand 7 (CCL7)+ fibroblasts, and interferon-induced protein with tetratricopeptide repeats 1 (IFIT1)+ neutrophils associated with disease relapse. These findings illuminate the tumor-immune crosstalk underlying treatment resistance and unveil promising therapeutic targets for overcoming lineage plasticity-driven resistance in advanced prostate cancer.
    Journal
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    TNFA (Tumor Necrosis Factor-Alpha) • TNFRSF1A (TNF Receptor Superfamily Member 1A) • VIM (Vimentin) • IFIT1 (Interferon Induced Protein With Tetratricopeptide Repeats 1) • GRN (Granulin Precursor)
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    Xtandi (enzalutamide)
    1m
    FASN inactivation-induced progranulin (GRN) expression promotes lysosome-dependent cell death to suppress leukemogenesis. (PubMed, Cell Rep)
    GRN depletion reverses the anti-leukemic effects of FASN loss. Our findings establish FASN as a therapeutic target and support its pharmacological inhibition by MS-C19 for leukemia treatment.
    Journal
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    FASN (Fatty acid synthase) • TFEB (Transcription Factor EB 2) • GRN (Granulin Precursor)
    2ms
    Phase 1/2 Clinical Trial of LY3884963 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN) (clinicaltrials.gov)
    P1/2, N=35, Active, not recruiting, Prevail Therapeutics | Recruiting --> Active, not recruiting | Trial completion date: Apr 2031 --> Nov 2029 | Trial primary completion date: Apr 2031 --> Nov 2029
    Enrollment closed • Trial completion date • Trial primary completion date • First-in-human
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    GRN (Granulin Precursor)
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    prednisone • sirolimus
    3ms
    ASPIRE-FTD: A Study to Evaluate the Safety and Effect of AVB-101, a Gene Therapy Product, in Subjects With a Genetic Sub-type of Frontotemporal Dementia (FTD-GRN) (clinicaltrials.gov)
    P1/2, N=9, Recruiting, AviadoBio Ltd | Trial completion date: Oct 2030 --> Mar 2030
    Trial completion date
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    GRN (Granulin Precursor)
    3ms
    A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL593 in Healthy Participants and Participants With Frontotemporal Dementia (FTD-GRN) (clinicaltrials.gov)
    P1/2, N=87, Active, not recruiting, Denali Therapeutics Inc. | Recruiting --> Active, not recruiting
    Enrollment closed
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    GRN (Granulin Precursor)
    4ms
    Phase 1/2 Clinical Trial of LY3884963 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN) (clinicaltrials.gov)
    P1/2, N=35, Recruiting, Prevail Therapeutics | Trial primary completion date: Apr 2030 --> Apr 2031 | Trial completion date: Apr 2030 --> Apr 2031
    Trial completion date • Trial primary completion date
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    GRN (Granulin Precursor)
    |
    prednisone • sirolimus
    5ms
    Targeting Granulin Haploinsufficiency in Frontotemporal Dementia: From Genetic Mechanisms to Therapeutics. (PubMed, Int J Mol Sci)
    Improved models and refined delivery systems would be essential to develop safe and effective treatments. Future work should also focus on biomarker-guided interventions in presymptomatic mutation carriers.
    Review • Journal
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    TARDBP (TAR DNA Binding Protein) • GRN (Granulin Precursor)
    7ms
    A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL593 in Healthy Participants and Participants With Frontotemporal Dementia (FTD-GRN) (clinicaltrials.gov)
    P1/2, N=106, Recruiting, Denali Therapeutics Inc. | Trial completion date: Dec 2026 --> Nov 2028
    Trial completion date
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    GRN (Granulin Precursor)
    7ms
    A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL593 in Healthy Participants and Participants With Frontotemporal Dementia (FTD-GRN) (clinicaltrials.gov)
    P1/2, N=106, Recruiting, Denali Therapeutics Inc. | Trial completion date: Nov 2025 --> Dec 2026 | Trial primary completion date: Nov 2025 --> Dec 2026
    Trial completion date • Trial primary completion date
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    GRN (Granulin Precursor)
    12ms
    Progranulin deficiency in the brain: the interplay between neuronal and non-neuronal cells. (PubMed, Transl Neurodegener)
    Specifically, we characterize the phenotypes of lipid droplet-accumulating microglia and alterations of myelin lipid content resulting from lysosomal dysfunction caused by PGRN deficiency. Additionally, we consider how the deregulation of glia-neuron communication affects the exchange of organelles such as mitochondria, and the removal of excess toxic products such as protein aggregates, in PGRN-related neurodegeneration.
    Review • Journal
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    TARDBP (TAR DNA Binding Protein) • GRN (Granulin Precursor)
    1year
    Phase 1/2 Clinical Trial of LY3884963 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN) (clinicaltrials.gov)
    P1/2, N=30, Recruiting, Prevail Therapeutics | Trial completion date: Aug 2029 --> Apr 2030 | Trial primary completion date: Aug 2029 --> Apr 2030
    Trial completion date • Trial primary completion date
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    GRN (Granulin Precursor)
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    prednisone • sirolimus
    1year
    Integrated multiomics analysis highlights the immunosuppressive role of granulin precursor positive macrophages in hepatocellular carcinoma. (PubMed, PeerJ)
    Functionally, GRN+ macrophages contacted with CD8+ T cells, which inducing T-cell exhaustion. Our study offers a comprehensive understanding of the clinical relevance and immunological role of GRN+ macrophages in HCC, indicating its potential role as a promising target for immunotherapeutic strategies.
    Journal • IO biomarker
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    CD8 (cluster of differentiation 8) • GRN (Granulin Precursor)