Author: Ogawa, Masahiro ; Sakai, Yosiki ; Motegi, Satoko ; Iwasawa, Takahiro ; Natsui, Kazuki ; Sawa, Yoshiki ; Terai, Shuji ; Nojiri, Shunsuke ; Tsuchiya, Atsunori ; Sato, Takeki ; Miyagawa, Shigeru ; Kumagai, Masaru ; Takeuchi, Suguru

AbstractBackgroundONO-1301 is a novel long-lasting prostaglandin (PG) I2 mimetic with inhibitory activity on thromboxane (TX) A2 synthase. This drug can also induce endogenous prostaglandin (PG)I2 and PGE2 levels. Furthermore, ONO-1301 acts as a cytokine inducer and can initiate tissue repair in a variety of diseases, such as pulmonary hypertension, pulmonary fibrosis, cardiac infarction, and obstructive nephropathy. In this study, our aim was to evaluate the effect of ONO-1301 on liver inflammation and fibrosis in a mouse model of non-alcoholic steatohepatitis (NASH).MethodsThe therapeutic effects of ONO-1301 against liver damage, fibrosis, and occurrence of liver tumors were evaluated using melanocortin 4 receptor-deficient (Mc4r-KO) NASH model mice. The effects of ONO-1301 against macrophages, hepatic stellate cells, and endothelial cells were also evaluated in vitro.ResultsONO-1301 ameliorated liver damage and fibrosis progression, was effective regardless of NASH status, and suppressed the occurrence of liver tumors in Mc4r-KO NASH model mice. In the in vitro study, ONO-1301 suppressed LPS-induced inflammatory responses in cultured macrophages, suppressed hepatic stellate cell (HSC) activation, upregulated vascular endothelial growth factor (VEGF) expression in HSCs, and upregulated hepatocyte growth factor (HGF) and VEGF expression in endothelial cells.ConclusionsThe results of our study highlight the potential of ONO-1301 to reverse the progression and prevent the occurrence of liver tumors in NASH using in vivo and in vitro models. ONO-1301 is a multidirectional drug that can play a key role in various pathways and can be further analyzed for use as a new drug candidate against NASH.

20 Nov 1999·Human Gene TherapyQ2 · MEDICINE

Cellular Immune Responses of Healthy Individuals to Intradermal Administration of an E1^-E3^-Adenovirus Gene Transfer Vector

Q2 · MEDICINE

Article

Author: Crystal, Ronald G. ; Harvey, Ben-Gary ; Worgall, Stefan ; Leopold, Philip L. ; Ely, Scott

In animals, Ad-mediated gene transfer initiates anti-Ad host immune responses that vary, depending on vector design, dose, host, and transgene. To begin to understand whether the anti-Ad vector responses in humans simulate those in animals, Ad(GV)CD.10, an E1-E3- Ad5 vector encoding the E. coli cytosine deaminase gene, was administered by the intradermal route to six normal individuals (8 x 10(7) to 8 x 10(9) particle units, each dose administered to two sites; n = 2 per group). No adverse events were observed. Polymerase chain reaction/Southern analysis demonstrated vector genome in the skin through 28 days in all individuals except one of two at the lowest dose. Local induration, independent of vector dose and baseline systemic anti-Ad5 neutralizing antibodies, developed in all subjects (6 to 17 mm, peak by day 3). Biopsies revealed a mild to moderate T cell (CD3+, CD4+, CD8+), B cell, and macrophage infiltrate at day 3, all decreased by day 28. Langerhans cells accumulated primarily in the papillary dermis. The day 3 cellular response was dose independent. On day 28, CD4+ and CD8+ T lymphocytes and macrophages showed dose dependency. There was minimal systemic Ad5-specific lymphocyte proliferation induced by Ad vector administration in three individuals studied, and no Ad5-specific cytotoxic T lymphocytes (evaluated in two subjects) could be detected. Thus, intradermal administration of an E1-E3- Ad vector to normal subjects induces mild/moderate local cellular responses, even in Ad-immunized individuals. These observations provide a baseline to determine if these human anti-Ad vector host responses can be circumvented by using "stealth" vectors and/or immunosuppression.

100 Deals associated with GV-1301

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Phase 1	-	GenVec, Inc.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

GV-1301

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation