Betty H. Baldwin
Cornell University
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Featured researches published by Betty H. Baldwin.
Journal of Hepatology | 2015
Stephan Menne; Daniel B. Tumas; Katherine H. Liu; Linta M. Thampi; Dalal AlDeghaither; Betty H. Baldwin; Christine A. Bellezza; Paul J. Cote; Jim Zheng; Randall L. Halcomb; Abigail Fosdick; Simon P. Fletcher; Stephane Daffis; Li Li; Peng Yue; Grushenka H.I. Wolfgang; Bud C. Tennant
BACKGROUND & AIMS New therapies for chronic hepatitis B (CHB) are urgently needed since current treatments rarely lead to cure. We evaluated whether the oral small molecule toll-like receptor (TLR7) agonist GS-9620 could induce durable antiviral efficacy in woodchucks chronically infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to human hepatitis B virus (HBV). METHODS After evaluating the pharmacokinetics, pharmacodynamics and tolerability of oral GS-9620 in uninfected woodchucks, adult woodchucks chronically infected with WHV (n = 7 per group) were dosed with GS-9620 or placebo for 4 or 8 weeks with different treatment schedules. RESULTS GS-9620 treatment induced rapid, marked and sustained reduction in serum viral DNA (mean maximal 6.2log10 reduction), and hepatic WHV DNA replicative intermediates, WHV cccDNA and WHV RNA, as well as loss of detectable serum WHV surface antigen (WHsAg). GS-9620 treatment also induced a sustained antibody response against WHsAg in a subset of animals. Strikingly, treatment reduced the incidence of hepatocellular carcinoma (HCC) from 71% in the placebo group to 8% in GS-9620-treated woodchucks with sustained viral load reduction. GS-9620 treatment was associated with reversible increases in serum liver enzymes and thrombocytopenia, and induced intrahepatic CD8(+) T cell, NK cell, B cell and interferon response transcriptional signatures. CONCLUSIONS The data demonstrate that short duration, finite treatment with the oral TLR7 agonist GS-9620 can induce a sustained antiviral response in the woodchuck model of CHB, and support investigation of this compound as a therapeutic approach to attain a functional cure in CHB patients.
Antiviral Chemistry & Chemotherapy | 1996
Prabhu Rajagopalan; F. D. Boudinot; Chung K. Chu; Bud C. Tennant; Betty H. Baldwin; Raymond F. Schinazi
The woodchuck (Marmota monax) is a useful animal model for evaluating the in-vivo efficacy of antiviral agents against hepatitis B viral infection (HBV). The pharmacokinetics of a newly synthesized antiviral agent (-)-β-D-2,6-diaminopurine dioxolane (DAPD) in woodchucks is reported. DAPD is a nucleoside analogue, having potent and selective activity against human immunodeficiency virus and HBV in vitro. DAPD is susceptible to deamination in vivo by the ubiquitously present enzyme adenosine deaminase yielding the active metabolite dioxolane guanosine (DXG). The pharmacokinetics of DAPD and DXG were characterized following intravenous (i.v.) and oral (p.o.) administration of 20 mg kg−1 of DAPD to woodchucks. Plasma and urine samples were collected, and nucleoside concentrations were determined by HPLC. Following intravenous administration, the half-life of DAPD averaged 6.7 ± 4.3 h, and that of DXG averaged 17.6 ± 14.5 h. The mean total clearance and steady state volume of distribution of DAPD were 0.33 ± 0.14 L h kg−1 and 1.76 ± 0.65 L kg−1, respectively. The oral bioavailability of DAPD ranged from 3.7-8.2%; however, the apparent availability of DXG following oral administration of DAPD was 10.5-53%.
Hepatology | 2001
Simon Peek; Paul J. Cote; James R. Jacob; Ilia Toshkov; William E. Hornbuckle; Betty H. Baldwin; Frances V. Wells; C. K. Chu; John L. Gerin; Bud C. Tennant; Brent Korba
Hepatology | 1998
Bud C. Tennant; Betty H. Baldwin; Lou Ann Graham; Mary Ascenzi; William E. Hornbuckle; Peter H. Rowland; Ilia A. Tochkov; Amy E. Yeager; Hollis N. Erb; Joseph M. Colacino; Carlos Lopez; Jeffery A. Engelhardt; Ronald R. Bowsher; Frank C. Richardson; William Lewis; Paul J. Cote; Brent E. Korba; John L. Gerin
Hepatology | 2000
Paul J. Cote; Brent Korba; Roger H. Miller; James R. Jacob; Betty H. Baldwin; William E. Hornbuckle; Robert H. Purcell; Bud C. Tennant; John L. Gerin
Journal of Virology | 1989
Brent Korba; Paul J. Cote; Frances V. Wells; Betty H. Baldwin; Hans Popper; Robert H. Purcell; Bud C. Tennant; John L. Gerin
Cancer Research | 1991
Rui Hai Liu; Betty H. Baldwin; Bud C. Tennant; Joseph H. Hotchkiss
Journal of Virology | 1991
C Seeger; Betty H. Baldwin; William E. Hornbuckle; A E Yeager; Bud C. Tennant; Paul J. Cote; L Ferrell; D Ganem; H E Varmus
Hepatology | 2000
Paul J. Cote; Ilia Toshkov; Christine A. Bellezza; Mary Ascenzi; Carol A. Roneker; Lou Ann Graham; Betty H. Baldwin; Karen Gaye; Ikuo Nakamura; Brent Korba; Bud C. Tennant; John L. Gerin
Antiviral Therapy | 2004
Brent E. Korba; Paul J. Cote; Stephen Menne; Ilia Toshkov; Betty H. Baldwin; Frances V. Wells; Bud C. Tennant; John L. Gerin