From Lab Bench to Hope: Emerging Gene Therapies in Clinical Trials for Alzheimer’s Disease

Andrade-Guerrero J, Santiago-Balmaseda A, Jeronimo-Aguilar P, Vargas-Rodríguez I, Cadena-Suárez AR, Sánchez-Garibay C, Pozo-Molina G, Méndez-Catalá CF et al (2023) Alzheimer’s disease: an updated overview of its genetics. Int J Mol Sci 24(4). https://doi.org/10.3390/ijms24043754

Tiwari S, Atluri V, Kaushik A, Yndart A, Nair M (2019) Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics. Int J Nanomedicine 14:5541–5554. https://doi.org/10.2147/IJN.S200490

Article  PubMed  PubMed Central  Google Scholar 

Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E (2011) Alzheimer’s disease. Lancet 377(9770):1019–1031. https://doi.org/10.1016/S0140-6736(10)61349-9

Article  PubMed  Google Scholar 

Parhizkar S, Holtzman DM (2022) APOE mediated neuroinflammation and neurodegeneration in Alzheimer’s disease. Semin Immunol 59:101594. https://doi.org/10.1016/j.smim.2022.101594

Article  PubMed  PubMed Central  Google Scholar 

Padda IS, Parmar M (2024) Aducanumab. In: StatPearls. StatPearls Publishing Copyright © 2024, StatPearls Publishing LLC., Treasure Island

Se Thoe E, Fauzi A, Tang YQ, Chamyuang S, Chia AYY (2021) A review on advances of treatment modalities for Alzheimer’s disease. Life Sci 276:119129. https://doi.org/10.1016/j.lfs.2021.119129

Article  PubMed  Google Scholar 

Honig LS, Barakos J, Dhadda S, Kanekiyo M, Reyderman L, Irizarry M, Kramer LD, Swanson CJ et al (2023) ARIA in patients treated with lecanemab (BAN2401) in a phase 2 study in early Alzheimer’s disease. Alzheimers Dement (N Y) 9(1):e12377. https://doi.org/10.1002/trc2.12377

Article  PubMed  Google Scholar 

Cummings J, Apostolova L, Rabinovici GD, Atri A, Aisen P, Greenberg S, Hendrix S, Selkoe D et al (2023) Lecanemab: appropriate use recommendations. J Prev Alzheimers Dis 10(3):362–377. https://doi.org/10.14283/jpad.2023.30

Article  PubMed  PubMed Central  Google Scholar 

Sperling RA, Jack CR, Black SE, Frosch MP, Greenberg SM, Hyman BT, Scheltens P, Carrillo MC et al (2011) Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer’s Association Research Roundtable Workgroup. Alzheimer’s Dement: J Alzheimers Assoc 7. https://doi.org/10.1016/j.jalz.2011.05.2351

van Dyck CH, Sabbagh M, Cohen S (2023) Lecanemab in early Alzheimer’s disease. Reply. N Engl J Med 388(17):1631–1632. https://doi.org/10.1056/NEJMc2301380

Article  PubMed  Google Scholar 

Chen W, Hu Y, Ju D (2020) Gene therapy for neurodegenerative disorders: advances, insights and prospects. Acta Pharm Sin B 10(8):1347–1359. https://doi.org/10.1016/j.apsb.2020.01.015

Article  PubMed  PubMed Central  Google Scholar 

Atchison RW, Casto BC, Hammon WM (1965) Adenovirus-associated defective virus particles. Science 149(3685):754–756. https://doi.org/10.1126/science.149.3685.754

Article  PubMed  Google Scholar 

Ling Q, Herstine JA, Bradbury A, Gray SJ (2023) AAV-based in vivo gene therapy for neurological disorders. Nat Rev Drug Discov 22(10):789–806. https://doi.org/10.1038/s41573-023-00766-7

Article  PubMed  Google Scholar 

Zhou K, Han J, Wang Y, Zhang Y, Zhu C (2022) Routes of administration for adeno-associated viruses carrying gene therapies for brain diseases. Front Mol Neurosci 15:988914. https://doi.org/10.3389/fnmol.2022.988914

Article  PubMed  PubMed Central  Google Scholar 

Zhao L, Gottesdiener AJ, Parmar M, Li M, Kaminsky SM, Chiuchiolo MJ, Sondhi D, Sullivan PM et al (2016) Intracerebral adeno-associated virus gene delivery of apolipoprotein E2 markedly reduces brain amyloid pathology in Alzheimer’s disease mouse models. Neurobiol Aging 44:159–172. https://doi.org/10.1016/j.neurobiolaging.2016.04.020

Article  PubMed  Google Scholar 

Mahley RW (2017) Apolipoprotein E: remarkable protein sheds light on cardiovascular and neurological diseases. Clin Chem 63(1):14–20. https://doi.org/10.1373/clinchem.2016.255695

Article  PubMed  Google Scholar 

Mahoney-Sanchez L, Belaidi AA, Bush AI, Ayton S (2016) The complex role of apolipoprotein E in Alzheimer’s disease: an overview and update. J Mol Neurosci 60(3):325–335. https://doi.org/10.1007/s12031-016-0839-z

Article  PubMed  Google Scholar 

Brookhouser N, Raman S, Frisch C, Srinivasan G, Brafman DA (2021) APOE2 mitigates disease-related phenotypes in an isogenic hiPSC-based model of Alzheimer’s disease. Mol Psychiatry 26(10):5715–5732. https://doi.org/10.1038/s41380-021-01076-3

Article  PubMed  PubMed Central  Google Scholar 

Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA et al (1997) Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA 278(16):1349–1356

Article  PubMed  Google Scholar 

Neu SC, Pa J, Kukull W, Beekly D, Kuzma A, Gangadharan P, Wang LS, Romero K et al (2017) Apolipoprotein E genotype and sex risk factors for Alzheimer disease: a meta-analysis. JAMA Neurol 74(10):1178–1189. https://doi.org/10.1001/jamaneurol.2017.2188

Article  PubMed  PubMed Central  Google Scholar 

Reiman EM, Arboleda-Velasquez JF, Quiroz YT, Huentelman MJ, Beach TG, Caselli RJ, Chen Y, Su Y et al (2020) Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study. Nat Commun 11(1):667. https://doi.org/10.1038/s41467-019-14279-8

Article  PubMed  PubMed Central  Google Scholar 

Litvinchuk A, Suh JH, Guo JL, Lin K, Davis SS, Bien-Ly N, Tycksen E, Tabor GT et al (2024) Amelioration of Tau and ApoE4-linked glial lipid accumulation and neurodegeneration with an LXR agonist. Neuron 112(3):384-403.e388. https://doi.org/10.1016/j.neuron.2023.10.023

Article  PubMed  Google Scholar 

Shi Y, Yamada K, Liddelow SA, Smith ST, Zhao L, Luo W, Tsai RM, Spina S et al (2017) ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy. Nature 549(7673):523–527. https://doi.org/10.1038/nature24016

Article  PubMed  PubMed Central  Google Scholar 

Zhao L, Gottesdiener AJ, Parmar M, Li M, Kaminsky SM, Chiuchiolo MJ, Sondhi D, Sullivan PM et al (2016) Intracerebral adeno-associated virus gene delivery of APOE2 markedly reduces brain amyloid pathology in Alzheimer’s disease mouse models. Neurobiol Aging 44:159–172

Article  PubMed  Google Scholar 

Serrano-Pozo A, Das S, Hyman BT (2021) APOE and Alzheimer’s disease: advances in genetics, pathophysiology, and therapeutic approaches. Lancet Neurol 20(1):68–80. https://doi.org/10.1016/S1474-4422(20)30412-9

Article  PubMed  PubMed Central  Google Scholar 

Lanfranco MF, Ng CA, Rebeck GW (2020) ApoE lipidation as a therapeutic target in Alzheimer’s disease. Int J Mol Sci 21(17). https://doi.org/10.3390/ijms21176336

Duro MV, Ebright B, Yassine HN (2022) Lipids and brain inflammation in APOE4-associated dementia. Curr Opin Lipidol 33(1):16–24. https://doi.org/10.1097/MOL.0000000000000801

Article  PubMed  PubMed Central  Google Scholar 

Zhao L, Gottesdiener AJ, Parmar M, Grevstad C, Havlicek D, Rosenberg J, Kaminsky S, Chiuchiolo M et al (2015) Gene delivery of APOE2 reduces amyloid pathology in transgenic mouse models of Alzheimer’s disease. Mol Ther 23:S154

Article  Google Scholar 

Li Z, Shue F, Zhao N, Shinohara M, Bu G (2020) APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease. Mol Neurodegener 15(1):63. https://doi.org/10.1186/s13024-020-00413-4

Article  PubMed  PubMed Central  Google Scholar 

Castellano JM, Kim J, Stewart FR, Jiang H, DeMattos RB, Patterson BW, Fagan AM, Morris JC et al (2011) Human apoE isoforms differentially regulate brain amyloid-β peptide clearance. Sci Transl Med 3(89):89ra57. https://doi.org/10.1126/scitranslmed.3002156

Article  PubMed  PubMed Central  Google Scholar 

Berlau DJ, Corrada MM, Head E, Kawas CH (2009) APOE epsilon2 is associated with intact cognition but increased Alzheimer pathology in the oldest old. Neurology 72(9):829–834. https://doi.org/10.1212/01.wnl.0000343853.00346.a4

Article  PubMed  PubMed Central  Google Scholar 

Endo Y, Hasegawa K, Nomura R, Arishima H, Kikuta KI, Yamashita T, Inoue Y, Ueda M et al (2019) Apolipoprotein E and clusterin inhibit the early phase of amyloid-β aggregation in an in vitro model of cerebral amyloid angiopathy. Acta Neuropathol Commun 7(1):12. https://doi.org/10.1186/s40478-019-0662-1

Article  PubMed  PubMed Central 

留言 (0)

沒有登入
gif