Methods for treating viral disorders

Inactive Publication Date: 2011-04-14
TRUSTEES OF BOSTON UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0018]In one aspect, the invention is directed to a method for treating a viral disorder in a subject, comprising providing said subject with at least one cycle of therapy, said cycle of therapy comprising: i) administering to the subject over a first period an inducing agent to induce expression of a viral gene product in a virus-infected cell of the subject and an anti-viral agent whose anti-viral activity is directed to the viral gene product expressed, wherein said first period of time is less than or equal to one-half o

Problems solved by technology

However, some Hodgkin's patients were seronegative for EBV, and the association between EBV and Hodgkin's disease remained speculative until 1987.
The close contact between T cells and the upper respiratory tract epithelium, known for its reservoir function for EBV, probably make T cells in this region more vulnerable for EBV infection.
The unique vulnerability of males with XLP to EBV infection is most likely due to an inherited immune regulatory defect that results in the failure to govern the cyto

Method used

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  • Methods for treating viral disorders
  • Methods for treating viral disorders
  • Methods for treating viral disorders

Examples

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example 1

Phase 1 Study of AB Plus Ganciclovir in Patients with EBV Associated Lymphoid Malignancies

[0130]Fifteen patients with EBV-associated lymphoid malignancies, who had histologically confirmed lymphoid neoplasms that were EBV+, were treated with AB and GCV. Prior therapies (varying in different subjects) included rituximab, chemotherapy, chemoradiotherapy and bone marrow transplant. GCV was administered at a rate of 5 mg / kg intravenously (IV) over 1 hour twice per day, and continued throughout the cycle. AB was continuously infused at a starting dose of 500 mg / kg / day. Dose escalation was continued as follows until MTD was established:

[0131]Level 1: 500 mg / kg / day IV for 2 days

[0132]Level 2: 1000 mg / kg / day IV for 2 days

[0133]Level 3: 1500 mg / kg / day IV for 2 days

[0134]Level 4: 2000 mg / kg / day IV until day 21

[0135]A total of 15 patients were evaluated for anti-tumor response (Table 1). A complete response (CR) was defined as disappearance of detectable malignant disease on imaging or physica...

example 2

Phase II Trial of Low-Dose Arginine Butyrate and Ganciclovir / Valganciclovir in EBV(+) Lymphoid Malignancies

[0140]It has previously been found that continuous infusion of inducing agent, for example, arginine butyrate, may not be necessary to maintain viral thymidine kinase expression and sensitization to anti-viral agents in EBV-associated tumors, but that, in fact, cells that survived initial exposure to the inducing agent plus the anti-viral agent remained susceptible to further cycles of combination treatment (Ghosh, S. K., et al. 2007Blood Cells, Molecules, and Diseases 38:57-65, incorporated herein in its entirety). However, it was neither anticipated nor expected that after some first period of treatment with inducing agent and anti-viral agent, one could continue the anti-viral treatment effectively within a cycle of therapy without continued administration of the inducing agent (continued administration including continued periods of pulsing throughout).

[0141]A clinical tria...

example 3

Analysis of Efficacy of the Herpes Anti-Virals

[0143]There are 12 mammalian HDACs, and any one of which might be required for repression of TK gene during latency in tumors. HDAC isozyme-specific siRNAs were used to to knockdown individual HDACs in tumor lines expressing latent EBV to determine which one of them induces reactivation of TK from latency, rendering it susceptible to anti-virals.

[0144]The EBV-positive B lymphoma cell line P3HR1 was used throughout these assays. The P3HR1 cell line was originally derived from Burkitt's lymphoma patient. EBV maintains a latent state of replication in this cell line. Cells were maintained in RPMI 1640 with 10% fetal bovine serum containing 100 U penicillin per ml and 100 μg streptomycin per ml. The HDAC inhibitors used were from five different classes: a) short chain fatty acids, b) hydroxamic acids, c) benzamides, d) cyclic tetrapeptides, and e) largazoles.

[0145]To measure the relative level of TK mRNA in various total RNA preparations, re...

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Abstract

Disclosed are methods of treating viral disorders via the administration of an inducing agent and an anti-viral agent. In one embodiment, the inducing agent and the anti-viral agent are administered for about five days, and the anti-viral agent is subsequently administered without the inducing agent for an additional period of about sixteen days for a total cycle of about 21 days.

Description

RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application No. 61 / 245,529, filed Sep. 24, 2009, and U.S. Provisional Application No. 61 / 295,663, filed Jan. 15, 2010, each of which is incorporated by reference herein in its entirety.BACKGROUND OF THE INVENTION[0002]A growing number of cellular disorders such as neoplastic malignancies have been found to contain viral genetic sequences or virus particles in the anomalous cells. For a large number of these disorders, the presence of the virus is believed to be a causative or at least contributory instrument. Representative members of many of the known families of viruses have been found in such cells including members of the herpes family of viruses, the polyomaviruses, and the hepatitis viruses. Epstein-Barr virus (EBV), a 172 kb herpes virus, is often found intimately associated with both mature and immature B cells. EBV is a common and worldwide pathogen. Childhood infection is asymptomatic. About ...

Claims

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Application Information

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IPC IPC(8): A61K31/522A61P31/12A61P35/00
CPCA61K31/00A61K45/06A61K31/166A61K38/15A61K31/223A61K31/522A61K38/12A61K31/185A61K31/198A61P31/12A61P35/00
Inventor PERRINE, SUSAN P.FALLER, DOUGLAS V.
Owner TRUSTEES OF BOSTON UNIV
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