Safety Findings of Dosing Gene Therapy Vectors in NHP With Pre-existing or Treatment-Emergent Anti-capsid Antibodies
We present safety findings from two 12-week studies in nonhuman primates (NHPs) with pre-existing or treatment-emergent antibodies. In the first study, NHPs with varying levels of naturally acquired anti-AAV5 antibodies were dosed with an AAV5-based vector encoding human factor VIII (hFVIII). In the second study, NHPs with no pre-existing anti-AAV antibodies were dosed with an AAV5-based vector carrying the beta subunit of choriogonadotropic hormone (bCG); this led to the induction of high-titer antibodies against the AAV5 capsid. Four weeks later, the same NHPs received an equivalent dose of an AAV5-based vector carrying ...
Source: Toxicologic Pathology - November 3, 2023 Category: Pathology Authors: Sundeep Chandra Brian R Long Carlos Fonck Andrew C Melton Jeremy Arens Jill Woloszynek Charles A O'Neill Source Type: research
Effects of LRRK2 Inhibitors in Nonhuman Primates
Toxicol Pathol. 2023 Nov 2:1926233231205895. doi: 10.1177/01926233231205895. Online ahead of print.ABSTRACTToxicology studies in nonhuman primates were conducted to evaluate selective, brain penetrant inhibitors of LRRK2. GNE 7915 was limited to 7-day administration in cynomolgus monkeys at 65 mg/kg/day or limited to 14 days in rhesus at 22.5 mg/kg b.i.d. due to physical signs. Compound 25 demonstrated acceptable tolerability at 50 and 225 mg/kg b.i.d. for 7 days in rhesus monkeys. MK-1468 was tolerated during 7-day administration at 100, 200 or 800 mg/kg/day or for 30-day administration at 30, 100, or 500 mg/kg b.i.d. in ...
Source: Toxicologic Pathology - November 2, 2023 Category: Pathology Authors: Glen K Miller Sabu Kuruvilla Binod Jacob Lisa LaFranco-Scheuch Vasudevan Bakthavatchalu Jason Flor Kristin Flor Julie Ziegler Christine Reichard Phil Manfre Suzanne Firner Tara McNutt Diane Quay Sairam Bellum Greg Doto Paul J Ciaccio Kara Pearson Jack Val Source Type: research
Can Historical Control Group Data Be Used to Replace Concurrent Controls in Animal Studies?
Toxicol Pathol. 2023 Oct 31:1926233231208987. doi: 10.1177/01926233231208987. Online ahead of print.ABSTRACTThe availability of large amounts of high-quality control data from tightly controlled regulated animal safety data has created the idea to re-use these data beyond its classical applications of quality control, identification of treatment-related effects and assessing effect-size relevance for building virtual control groups (VCGs). While the ethical and cost-saving aspects of such a concept are immediately evident, the potential challenges need to be carefully considered to avoid any effect which could lower the se...
Source: Toxicologic Pathology - October 31, 2023 Category: Pathology Authors: Thomas Steger-Hartmann Matthew Clark Source Type: research
Can Historical Control Group Data Be Used to Replace Concurrent Controls in Animal Studies?
Toxicol Pathol. 2023 Oct 31:1926233231208987. doi: 10.1177/01926233231208987. Online ahead of print.ABSTRACTThe availability of large amounts of high-quality control data from tightly controlled regulated animal safety data has created the idea to re-use these data beyond its classical applications of quality control, identification of treatment-related effects and assessing effect-size relevance for building virtual control groups (VCGs). While the ethical and cost-saving aspects of such a concept are immediately evident, the potential challenges need to be carefully considered to avoid any effect which could lower the se...
Source: Toxicologic Pathology - October 31, 2023 Category: Pathology Authors: Thomas Steger-Hartmann Matthew Clark Source Type: research
Can Historical Control Group Data Be Used to Replace Concurrent Controls in Animal Studies?
Toxicol Pathol. 2023 Oct 31:1926233231208987. doi: 10.1177/01926233231208987. Online ahead of print.ABSTRACTThe availability of large amounts of high-quality control data from tightly controlled regulated animal safety data has created the idea to re-use these data beyond its classical applications of quality control, identification of treatment-related effects and assessing effect-size relevance for building virtual control groups (VCGs). While the ethical and cost-saving aspects of such a concept are immediately evident, the potential challenges need to be carefully considered to avoid any effect which could lower the se...
Source: Toxicologic Pathology - October 31, 2023 Category: Pathology Authors: Thomas Steger-Hartmann Matthew Clark Source Type: research
Pathological Characterization of Spontaneous AA Amyloidosis in Microminipigs
This study demonstrates that microminipigs with wild-type SAA develop AA amyloidosis and presents the possibility that differences in the environment surrounding amyloid, such as SAP, may influence differences in the pathological phenotype.PMID:37873595 | DOI:10.1177/01926233231204019 (Source: Toxicologic Pathology)
Source: Toxicologic Pathology - October 24, 2023 Category: Pathology Authors: Misaki Inoue Shinya Miyazaki Natsumi Kobayashi Akihisa Kangawa Tomoaki Murakami Source Type: research
Pathological Characterization of Spontaneous AA Amyloidosis in Microminipigs
This study demonstrates that microminipigs with wild-type SAA develop AA amyloidosis and presents the possibility that differences in the environment surrounding amyloid, such as SAP, may influence differences in the pathological phenotype.PMID:37873595 | DOI:10.1177/01926233231204019 (Source: Toxicologic Pathology)
Source: Toxicologic Pathology - October 24, 2023 Category: Pathology Authors: Misaki Inoue Shinya Miyazaki Natsumi Kobayashi Akihisa Kangawa Tomoaki Murakami Source Type: research
Pathological Characterization of Spontaneous AA Amyloidosis in Microminipigs
This study demonstrates that microminipigs with wild-type SAA develop AA amyloidosis and presents the possibility that differences in the environment surrounding amyloid, such as SAP, may influence differences in the pathological phenotype.PMID:37873595 | DOI:10.1177/01926233231204019 (Source: Toxicologic Pathology)
Source: Toxicologic Pathology - October 24, 2023 Category: Pathology Authors: Misaki Inoue Shinya Miyazaki Natsumi Kobayashi Akihisa Kangawa Tomoaki Murakami Source Type: research
Pathological Characterization of Spontaneous AA Amyloidosis in Microminipigs
This study demonstrates that microminipigs with wild-type SAA develop AA amyloidosis and presents the possibility that differences in the environment surrounding amyloid, such as SAP, may influence differences in the pathological phenotype.PMID:37873595 | DOI:10.1177/01926233231204019 (Source: Toxicologic Pathology)
Source: Toxicologic Pathology - October 24, 2023 Category: Pathology Authors: Misaki Inoue Shinya Miyazaki Natsumi Kobayashi Akihisa Kangawa Tomoaki Murakami Source Type: research
Pathological Characterization of Spontaneous AA Amyloidosis in Microminipigs
This study demonstrates that microminipigs with wild-type SAA develop AA amyloidosis and presents the possibility that differences in the environment surrounding amyloid, such as SAP, may influence differences in the pathological phenotype.PMID:37873595 | DOI:10.1177/01926233231204019 (Source: Toxicologic Pathology)
Source: Toxicologic Pathology - October 24, 2023 Category: Pathology Authors: Misaki Inoue Shinya Miyazaki Natsumi Kobayashi Akihisa Kangawa Tomoaki Murakami Source Type: research
Pathological Characterization of Spontaneous AA Amyloidosis in Microminipigs
This study demonstrates that microminipigs with wild-type SAA develop AA amyloidosis and presents the possibility that differences in the environment surrounding amyloid, such as SAP, may influence differences in the pathological phenotype.PMID:37873595 | DOI:10.1177/01926233231204019 (Source: Toxicologic Pathology)
Source: Toxicologic Pathology - October 24, 2023 Category: Pathology Authors: Misaki Inoue Shinya Miyazaki Natsumi Kobayashi Akihisa Kangawa Tomoaki Murakami Source Type: research
An Overview of Nonclinical and Clinical Liver Toxicity Associated With AAV Gene Therapy
This article reviews the presentation given at the 2023 annual meeting of the Society of Toxicologic Pathology (STP) on liver toxicity observed with adeno-associated viral vector (AAV) gene therapy. After decades as a therapeutic modality largely confined to the academic research environment, gene therapy has emerged in recent years as a rapidly expanding therapeutic approach in the biopharmaceutical industry with AAV as the most commonly used viral vector for gene delivery. This interest in the field of gene therapy by industry has been enhanced by the recent success of approved therapies for curing genetic diseases such ...
Source: Toxicologic Pathology - September 29, 2023 Category: Pathology Authors: Laurence O Whiteley Source Type: research
An Overview of Nonclinical and Clinical Liver Toxicity Associated With AAV Gene Therapy
This article reviews the presentation given at the 2023 annual meeting of the Society of Toxicologic Pathology (STP) on liver toxicity observed with adeno-associated viral vector (AAV) gene therapy. After decades as a therapeutic modality largely confined to the academic research environment, gene therapy has emerged in recent years as a rapidly expanding therapeutic approach in the biopharmaceutical industry with AAV as the most commonly used viral vector for gene delivery. This interest in the field of gene therapy by industry has been enhanced by the recent success of approved therapies for curing genetic diseases such ...
Source: Toxicologic Pathology - September 29, 2023 Category: Pathology Authors: Laurence O Whiteley Source Type: research
An Overview of Nonclinical and Clinical Liver Toxicity Associated With AAV Gene Therapy
This article reviews the presentation given at the 2023 annual meeting of the Society of Toxicologic Pathology (STP) on liver toxicity observed with adeno-associated viral vector (AAV) gene therapy. After decades as a therapeutic modality largely confined to the academic research environment, gene therapy has emerged in recent years as a rapidly expanding therapeutic approach in the biopharmaceutical industry with AAV as the most commonly used viral vector for gene delivery. This interest in the field of gene therapy by industry has been enhanced by the recent success of approved therapies for curing genetic diseases such ...
Source: Toxicologic Pathology - September 29, 2023 Category: Pathology Authors: Laurence O Whiteley Source Type: research
An Overview of Nonclinical and Clinical Liver Toxicity Associated With AAV Gene Therapy
This article reviews the presentation given at the 2023 annual meeting of the Society of Toxicologic Pathology (STP) on liver toxicity observed with adeno-associated viral vector (AAV) gene therapy. After decades as a therapeutic modality largely confined to the academic research environment, gene therapy has emerged in recent years as a rapidly expanding therapeutic approach in the biopharmaceutical industry with AAV as the most commonly used viral vector for gene delivery. This interest in the field of gene therapy by industry has been enhanced by the recent success of approved therapies for curing genetic diseases such ...
Source: Toxicologic Pathology - September 29, 2023 Category: Pathology Authors: Laurence O Whiteley Source Type: research
