A Phase I Study to Assess the Safety, Tolerability and Preliminary Efficacy of AAV2-BDNF [Adeno-Associated Virus (AAV)-Based, Vector-Mediated Delivery of Human Brain Derived Neurotrophic Factor] in Subjects With Early Alzheimer's Disease and Mild Cognitive Impairment

This is a first-in-human clinical trial to test whether a protein administered into the brain continuously by gene therapy, Brain-Derived Neurotrophic Factor (BDNF), will slow or prevent cell loss in the brains of people affected by Alzheimer's disease and Mild Cognitive Impairment. The protein may also activate cells in the brain that have not yet deteriorated. Gene therapy refers to the use of a harmless virus to have brain cells make the potentially protective protein, BDNF.

开始日期2022-02-07

申办/合作机构

University of California San Diego

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100 项与 AAV2-BDNF Gene Therapy(Case Western Reserve University) 相关的临床结果

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100 项与 AAV2-BDNF Gene Therapy(Case Western Reserve University) 相关的转化医学

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100 项与 AAV2-BDNF Gene Therapy(Case Western Reserve University) 相关的专利（医药）

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项与 AAV2-BDNF Gene Therapy(Case Western Reserve University) 相关的文献（医药）

2024-11-01·eneuro

Comparative Analysis of Six Adeno-Associated Viral Vector Serotypes in Mouse Inferior Colliculus and Cerebellum

Article

作者: Witteveen, Isabelle ; Balmer, Timothy

Adeno-associated viral vector (AAV) serotypes vary in how effectively they express genes across different cell types and brain regions. Here we report a systematic comparison of the AAV serotypes 1, 2, 5, 8, 9, and the directed evolution derived AAVrg, in the inferior colliculus (IC) and cerebellum. The AAVs were identical apart from their different serotypes, each having a synapsin promotor and expressing GFP (AAV-hSyn-GFP). Identical titers and volumes were injected into the IC and cerebellum of adult male and female mice, and brains were sectioned and imaged 2 weeks later. Transduction efficacy, anterograde labeling of axonal projections, and retrograde labeling of somata were characterized and compared across serotypes. Cell-type tropism was assessed by analyzing the morphology of the GFP-labeled neurons in the cerebellar cortex. In both the cerebellum and IC, AAV1 expressed GFP in more cells, labeled a larger volume, and produced significantly brighter labeling than all other serotypes, indicating superior transgene expression. AAV1 labeled more Purkinje cells, unipolar brush cells, and molecular layer interneurons than the other serotypes, while AAV2 labeled a greater number of granule cells. These results provide guidelines for the use of AAVs as gene delivery tools in these regions.

2024-05-01·Gene Therapy

Multicenter assessment and longitudinal study of the prevalence of antibodies and related adaptive immune responses to AAV in adult males with hemophilia

Article

作者: Negrier, Claude ; Konkle, Barbara A ; Ayash-Rashkovsky, Mila ; Pabinger, Ingrid ; Mingot-Castellano, María Eva ; Yan, Brian ; Escobar, Miguel ; Rajavel, Kavitha ; Mullins, Eric S ; Pan, Luying ; Chapin, John

AbstractAdeno-associated virus (AAV) based gene therapy has demonstrated effective disease control in hemophilia. However, pre-existing immunity from wild-type AAV exposure impacts gene therapy eligibility. The aim of this multicenter epidemiologic study was to determine the prevalence and persistence of preexisting immunity against AAV2, AAV5, and AAV8, in adult participants with hemophilia A or B. Blood samples were collected at baseline and annually for ≤3 years at trial sites in Austria, France, Germany, Italy, Spain, and the United States. At baseline, AAV8, AAV2, and AAV5 neutralizing antibodies (NAbs) were present in 46.9%, 53.1%, and 53.4% of participants, respectively; these values remained stable at Years 1 and 2. Co-prevalence of NAbs to at least two serotypes and all three serotypes was present at baseline for ~40% and 38.2% of participants, respectively. For each serotype, ~10% of participants who tested negative for NAbs at baseline were seropositive at Year 1. At baseline, 38.3% of participants had detectable cell mediated immunity by ELISpot, although no correlations were observed with the humoral response. In conclusion, participants with hemophilia may have significant preexisting immunity to AAV capsids. Insights from this study may assist in understanding capsid-based immunity trends in participants considering AAV vector-based gene therapy.

2024-05-01·Molecular Therapy

Gene therapy approaches for obesity-induced adipose neuropathy: Device-targeted AAV-mediated neurotrophic factor delivery to adipocytes in subcutaneous adipose

Article

作者: Blaszkiewicz, Magdalena ; Cao, Lei ; Tao, Tianyi ; Mensah-Arhin, Kofi ; Smith, Rosemary L ; Bates, Rhiannon ; Willows, Jake W ; Huang, Wei ; Townsend, Kristy L

Maintaining functional adipose innervation is critical for metabolic health. We found that subcutaneous white adipose tissue (scWAT) undergoes peripheral neuropathy (PN) with obesity, diabetes, and aging (reduced small-fiber innervation and nerve/synaptic/growth-cone/vesicle markers, altered nerve activity). Unlike with nerve injuries, peripheral nerves do not regenerate with PN, and therefore new therapies are needed for treatment of this condition affecting 20-30 million Americans. Here, we validated a gene therapy approach using an adipocyte-tropic adeno-associated virus (AAV; serotype Rec2) to deliver neurotrophic factors (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) directly to scWAT to improve tissue-specific PN as a proof-of-concept approach. AAVRec2-BDNF intra-adipose delivery improved tissue innervation in obese/diabetic mice with PN, but after longer periods of dietary obesity there was reduced efficacy, revealing a key time window for therapies. AAVRec2-NGF also increased scWAT innervation in obese mice and was more effective than BDNF, likely because Rec2 targeted adipocytes, the tissue's endogenous NGF source. AAVRec2-NGF also worked well even after 25 weeks of dietary obesity, unlike BDNF, which likely needs a vector that targets its physiological cellular source (stromal vascular fraction cells). Given the differing effects of AAVs carrying NGF versus BDNF, a combined therapy may be ideal for PN.

100 项与 AAV2-BDNF Gene Therapy(Case Western Reserve University) 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
轻度认知障碍	临床1期	美国	University of California San Diego	2022-02-07
家族性阿尔茨海默病3型	药物发现	美国	University of California San Diego	2021-03-01
帕金森病	药物发现	美国	University of California San Diego	2021-03-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASGCT2020	临床2期	阿尔茨海默症	-	AAV2-NGF gene therapy	醖鹹獵範構廠蓋糧醖廠(製鹽鑰積鬱鹹網齋鹹壓) = 壓鬱壓醖積鬱壓鑰網繭範鹽鏇構鏇襯糧鹽衊夢 (憲願蓋淵鏇窪憲遞窪觸 ) 更多	积极	2020-04-28
				AAV2-BDNF gene therapy	齋膚壓構網艱願範簾壓(遞餘顧鬱膚襯鬱願構糧) = 艱鹹鹽淵鏇艱醖範窪獵觸觸積願網鬱壓鏇襯選 (鹽構壓醖築鏇夢鑰糧繭 )