Use of Model-informed Drug Development and Natural History Data to Inform the Development of Iluzanebart in ALSP: A Rare Adult-Onset Neurodegenerative Leukoencephalopathy
F. Gaudreault, et al. American Conference on Pharmacometrics
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Phase 1, First-in-Human, Single- and Multiple-Ascending Dose Study of a Novel Orally Administered TREM2 Agonist (VG-3927) in Healthy Volunteers: Interim Results
R. Rajagovindan, et al. Clinical Trials on Alzheimer’s Disease
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Mapping the journey of patients and care partners living with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: developing a framework for improvements in care
H.A. Rutherford, et al. Neurodegenerative Disease Management
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Orally Administered Small Molecule TREM2 Agonists for Modulating AD Pathophysiology
C. Mirescu, et al. Alzheimer's Association International Conference
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Pharmacological and Functional Characterization of the First Small Molecule TREM2 Agonist, VG-3927, for the Treatment of Alzheimer’s disease
C. Mirescu, et al. Alzheimer's Association International Conference
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Design of a Phase 1, First-in-Human, Randomized, Double-Blind, Placebo-Controlled, Single- and Multiple-Ascending Dose Study of a Novel Orally Administered TREM2 Agonist (VG-3927) in Healthy Volunteers
R. Rajagovindran, et al. Alzheimer's Association International Conference
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Clinical Overlap of ALSP and Movement Disorders: Impact of Misdiagnosis on a Patient’s Journey
A. Meier, et al. World Congress on Parkinsonism and Related Disorders
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Leveraging Community Insights to Map the ALSP Patient Journey: Misdiagnosis and Genetic Testing
H.A. Rutherford, et al. Rare Drug Development Symposium
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IGNITE Phase 2 Trial of Iluzanebart (VGL101) in Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia (ALSP)
Zbigniew Wszolek, et al. 2024 American Academy of Neurology (AAN) Annual Meeting, Presentation S28.005
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VGL101: A TREM2 Immunotherapy that Enhances Microglial Survival for Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP)
Abbie Renoux, et al. 2024 American Academy of Neurology (AAN) Annual Meeting, Poster 013
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Findings From the ILLUMINATE Prospective Natural History Study (NHS) in Individuals with Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP)
David S. Lynch, et al. 2024 American Academy of Neurology (AAN) Annual Meeting, Poster P3.001
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Clinical presentation and diagnosis of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: a literature analysis of case studies
Papapetropoulos et al. Front. Neurol., 2024 Mar 11;15:1320663.
https://doi.org/10.3389/fneur.2024.1320663
Clinical Overlap of ALSP as Multiple Sclerosis - Impact of Misdiagnosis and Genetic Testing on the ALSP Patient Journey
R. La Piana, H. A. Rutherford, et al. The ninth annual Americas Committee for Treatment and Research in Multiple Sclerosis Forum (ACTRIMS 2024), Poster Session 1
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A Phase 1, First-in-Human, Randomized, Double-Blind, Placebo-Controlled, Single- and Multiple-Ascending Intravenous Dose Study of VGL101, a Novel TREM2 Agonist, in Healthy Adult Volunteers
Andreas Meier, et al. The 148th Annual Meeting of the American Neurological Association (ANA 2023), Poster M151
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IGNITE: A Phase 2 Proof-of-Concept Study of VGL 101 in Patients with Adult-onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP)
Jeffrey Gelfand, et al. The 148th Annual Meeting of the American Neurological Association (ANA 2023), Poster LB-M106
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Unique MoA of Highly Potent, Orally Bioavailable and Brain Penetrant Small Molecule TREM2 Agonists for the Potential Treatment of Alzheimer's Disease
Borislav Dejanović, et al. 2023 Keystone Symposia on Molecular and Cellular Biology - Neurodegeneration: New Biology Guiding the Next Generation of Therapeutic Development, Workshop 2: Emerging Topics on Therapeutic Intervention of Neurodegenerative Disorder (Z4)
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Unique Mechanism of Action of Highly Potent, Orally Bioavailable and Brain Penetrant Small Molecule TREM2 Agonists for the Potential Treatment of Alzheimer’s Disease
Matthew D. Figley, et al. 2023 Keystone Symposia on Molecular and Cellular Biology - Neurodegeneration: New Biology Guiding the Next Generation of Therapeutic Development, Poster Session 3
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Refining the phenotype of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a commonly misdiagnosed autosomal dominant neurodegenerative disease
Andreas Meier, et al. The 2023 American Academy of Neurology (AAN) Annual Meeting – S49: General Neurology, Oral Presentation 010
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A Prospective Natural History Study of Patients with Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP)
Raj Rajagovindan, et al. The 2023 American Academy of Neurology (AAN) Annual Meeting – S49: General Neurology, Oral Presentation 008
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Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is commonly misdiagnosed as Frontotemporal Dementia (FTD), Multiple Sclerosis (MS), Alzheimer’s disease (AD), or other adult-onset leukodystrophies
Andreas Meier, et al. The 2023 American Academy of Neurology (AAN) Annual Meeting – P12: General Neurology: Neurogenetics 2, Poster 003
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Radiological features of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its longitudinal progression
Raj Rajagovindan, et al. The 2023 American Academy of Neurology (AAN) Annual Meeting – P8: General Neurology: Neuroimaging, Oral Presentation 003
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A Phase 1, First-in-human, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Intravenous Dose Study of a novel TREM2 agonist (VGL101) in Healthy Volunteers (HVs)
Andreas Meier, et al. The 2023 American Academy of Neurology (AAN) Annual Meeting – S14: General Neurology: Emerging Therapies, Oral Presentation 004
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Characterization of highly potent, orally bioavailable, and brain penetrant small molecule TREM2 agonists for the potential treatment of Alzheimer’s disease
Christian Mirescu. AD/PD 2023 International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders – Onsite Hall G4; Symposium: TREM2, Microglia, Astrocytes
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Leveraging precision medicine for TREM2-targeted therapeutics in Alzheimer’s disease
Raj Rajagovindan et al. AD/PD 2023 International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders – A04.H. Imaging, Biomarkers, Diagnostics: CSF, Blood, Body Fluid Biomarkers, Poster 0428
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Adult Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) Misdiagnosed as Multiple Sclerosis (MS) or Other Adult Onset Leukodystrophies
Andreas Meier et al. The 8th Annual Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum – Poster Session 1, Poster 127
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Phenotypic Features of Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP): Presenting Symptoms and Clinical Course
Spyros Papapetropoulos et al. The 2022 Alzheimer's Association International Conference (AAIC) - P2-08 Clinical Manifestations: Neuropsychiatry and Behavioral Neurology, Poster 258
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VGL101 Rescues CSF1R Dysfunction in Human Microglia and Macrophages: Evaluation of In Vitro TREM2 Agonism in Models of a CSF1R-dependent Leukodystrophy
Daria Tchessalova et al. The 2022 Alzheimer's Association International Conference (AAIC) - P2-05 Basic Science and Pathogenesis: Molecular and Cell Biology, Poster 090
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EPV-631 Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP): Initial Misdiagnosis
Spyros Papapetropoulos et al. 8th Congress of the European Academy of Neurology - Europe 2022
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Genotype-phenotype correlations in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)
Spyros Papapetropoulos et al. The 2022 American Academy of Neurology (AAN) Annual Meeting – P11 Aging and Dementia: Non-Alzheimer's Dementia: Genetics and Neuroimaging 1, Poster 002
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Survival analysis of patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP): data from a systematic literature review of published case studies
Spyros Papapetropoulos et al. The 2022 American Academy of Neurology (AAN) Annual Meeting – P5 Neuroepidemiology 2, Poster 002
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Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia: Review of Clinical Manifestations as Foundations for Therapeutic Development
Papapetropoulos et al. Front. Neurol., 2022 Feb 03; 12:788168.
https://doi.org/10.3389/fneur.2021.788168
Activated microglia mitigate Aβ-associated tau seeding and spreading
Gratuze et al. Journal of Exp Med 2021 Jun; 218(8):e20210542
https://doi.org/10.1084/jem.20210542
Trem2 restrains the enhancement of tau accumulation and neurodegeneration by β-amyloid pathology
Lee et al. Neuron 2021; 109,8:1283-1301.e6.
https://pubmed.ncbi.nlm.nih.gov/33675684/
The most prevalent rare coding variants of TREM2 conferring risk of Alzheimer's disease: A systematic review and meta-analysis
Li et al. Exp Ther Med. 2021 Apr;21(4):347.
https://pubmed.ncbi.nlm.nih.gov/33732320/
Dynamic analysis of CSF1R-related leukoencephalopathy on magnetic resonance imaging: a case report
Huang et al. BMC Neurology 2021; 21,156
https://doi.org/10.1186/s12883-021-02182-z
Attenuated CSF-1R signaling drives cerebrovascular pathology
Delaney et al. EMBO Molecular Medicine 2021; 13,2: e12889
https://www.embopress.org/doi/full/10.15252/emmm.202012889
Microglia modulate neurodegeneration in Alzheimer’s and Parkinson’s diseases
Bartels et al. Science 2020 Oct 2;370(6512):66-69
https://science.sciencemag.org/content/370/6512/66
Anti-human TREM2 induces microglia proliferation and reduces pathology in an Alzheimer's disease model
Wang et al. Journal of Exp Med 2020; 217,9: e20200785.
https://pubmed.ncbi.nlm.nih.gov/32579671/
Whole exome sequencing study identifies novel rare and common Alzheimer’s-Associated variants involved in immune response and transcriptional regulation
Bis et al. Mol Psychiatry 2020; 25,1859–1875
https://doi.org/10.1038/s41380-018-0112-7
The Physiology, Pathology, and Potential Therapeutic Applications of the TREM2 Signaling Pathway
Deczkowska et al. Cell 2020 Jun 11;181(6):1207-1217
https://www.sciencedirect.com/science/article/abs/pii/S0092867420305651
Loss of homeostatic microglial phenotype in CSF1R-related Leukoencephalopathy
Kempthorne et al. Acta Neuropathol Commun 2020 May 19;8(1):72
https://pubmed.ncbi.nlm.nih.gov/32430064/
Factors predictive of the presence of a CSF1R mutation in patients with leukoencephalopathy
Kondo et al. Eur J Neurol 2020 Feb;27(2):369-375
https://pubmed.ncbi.nlm.nih.gov/31520500/
Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE
Parhizkar et al. Nature Neuroscience 2019; 22:191–204
https://doi.org/10.1038/s41593-018-0296-9
Assessment of the Genetic Architecture of Alzheimer's Disease Risk in Rate of Memory Decline
Del-Aguila JL et al. Alzheimers Dis. 2018;62(2):745-756
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989565/
CSF1R-related leukoencephalopathy - A major player in primary microgliopathies
Konno et al. Neurology 2018 Dec 11;91(24):1092-1104
https://pubmed.ncbi.nlm.nih.gov/30429277/
NfL is a biomarker for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia
Hayer et al. Neurology 2018 Oct 16;91(16):755-757
https://pubmed.ncbi.nlm.nih.gov/30217938/
Early-onset dementia, leukoencephalopathy and brain calcifications: a clinical, imaging and pathological comparison of ALSP and PLOSL/Nasu Hakola disease
Coomans et al. Acta Neurologica Belgica 2018; 118,4:607-615.
https://pubmed.ncbi.nlm.nih.gov/30242731/
Molecular basis for the loss-of-function effects of the Alzheimer's disease-associated R47H variant of the immune receptor TREM2
Sudom et al. J Biol Chem 2018 Aug 10;293(32):12634-12646
https://pubmed.ncbi.nlm.nih.gov/29794134/
TREM2-activating antibodies abrogate the negative pleiotropic effects of the Alzheimer's disease variant Trem2R47H on murine myeloid cell function
Cheng et al. J Biol Chem 2018 Aug 10;293(32):12620-12633
https://pubmed.ncbi.nlm.nih.gov/29599291/
Colony-Stimulating Factor 1 Receptor (CSF1R) Regulates Microglia Density and Distribution, but Not Microglia Differentiation In Vivo
Oosterhof et al. Cell Reports 2018 Jul 31;24(5):1203-1217.e6
https://pubmed.ncbi.nlm.nih.gov/30067976/
Diagnostic criteria for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia due to CSF1R mutation
Konno et al. Eur J Neurol 2018 Jan;25(1):142-7.
https://pubmed.ncbi.nlm.nih.gov/28921817/
Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease: lesion staging and dynamic changes of axons and microglial subsets
Oyanagi et al. Brain Pathol 2017 Nov;27(6):748-769
https://pubmed.ncbi.nlm.nih.gov/27608278/
Redefining the phenotype of ALSP and AARS2 mutation-related leukodystrophy
Lakshmanan et al. Neurology Genetics 2017; 3,2 e135
https://ng.neurology.org/content/3/2/e135
Clinical and genetic characterization of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia associated with CSF1R mutation
Konno et al. Eur J Neurol. 2017 Jan;24(1):37-45.
https://pubmed.ncbi.nlm.nih.gov/27680516/
TREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy
Yuan et al. Neuron 2016 May 18;90(4):724-39
https://pubmed.ncbi.nlm.nih.gov/27196974/
Hereditary leukoencephalopathy with axonal spheroids: a spectrum of phenotypes from CNS vasculitis to parkinsonism in an adult onset leukodystrophy series
Lynch et al. J Neurol Neurosurg Psychiatry. 2016 May;87(5):512-9.
https://doi.org/10.1136/jnnp-2015-310788
A practical approach to diagnosing adult onset leukodystrophies
Ahmed et al. J Neurol Neurosurg Psychiatry. 2014 Jul;85(7):770-81.
https://doi.org/10.1136/jnnp-2013-305888
TREM2 variants in Alzheimer's disease
Guerreiro et al. N Engl J Med. 2013;368(2):117-127.
https://www.nejm.org/doi/full/10.1056/nejmoa1211851
CSF1R-Related Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia
Sundal & Wszolek. 2012 Aug 30 [updated 2017 Oct 5]. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2021. PMID: 22934315
https://www.ncbi.nlm.nih.gov/books/NBK100239/
MRI characteristics and scoring in HDLS due to CSF1R gene mutations
Sundal et al. Neurology 2012 Aug 7;79(6):566-74
https://pubmed.ncbi.nlm.nih.gov/22843259/
Mutations in the colony stimulating factor 1 receptor (CSF1R) cause hereditary diffuse leukoencephalopathy with spheroids
Rademakers et al. Nat Genet. 2012 Feb; 44(2): 200-205
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3267847/
Nasu–Hakola disease and primary microglial dysfunction
Bianchin et al. Nat Rev Neurol 2010; 6, 523
https://doi.org/10.1038/nrneurol.2010.17-c1
