Cytomegalovirus Infection: PG36

Introduction

Herbs that stimulate the immune system are described in TCM as adding tone to ‘Qi’ (energy), the blood, the Yin and the Yang.  Although the immune system, like the hematopoietic system is generally robust, enhancement of the immune system is sometimes advantageous, particularly when it has been compromised by viral infections such as CMV (cytomegalovirus) or AIDS.  Of plants tested for immune potentiating activity, four extracts produced a good response in protecting immune compromised mice from lethal viral infection.  Extracts from the B36 plant were further purified and confirmed to exhibit activity against CMV infection.

CMV Infection

Among pathogenic agents that cause opportunistic infections in humans, CMV is a major problem for individuals whose immune systems are underdeveloped (e.g., neonates and cases of genetic immunodeficiency), or compromised artificially (transplant or cancer patients undergoing chemotherapy or irradiation), or by a preexisting infection such as the human immunodeficiency virus (HIV).  After an acute primary infection in a healthy subject, the virus becomes latent and reactivation can be triggered repeatedly in response to various factors that can lead to immune suppression. In transplant patients, CMV is the most frequent viral infection aside from Epstein-Barr virus, another herpesvirus.  The source and target of CMV infection is often the transplanted organ itself, with virus replication and spread to other organs aided by immunosuppressive treatments to prevent graft rejection.  In many cases, transplant recipients with latent CMV infection will experience reactivation after chemotherapy.  CMV infection is a significant factor in graft rejection and chronic graft dysfunction, and CMV infection has been linked with decreased long-term survival of liver, cardiac and lung transplant recipients.  Murine CMV infection has several features in common with human CMV infection and may serve as an animal model for human CMV infection.

CMV Market Overview

About 25% of bone marrow and organ transplant recipients develop CMV pneumonitis ([1]). Infection may be primary (60%), reactivation (<20%), or superinfection (20-50%).  The transplanted organ is particularly vulnerable as a target for CMV infection (e.g., CMV hepatitis follows liver transplantation). CMV is certainly the most important pathogen affecting transplant patients. The Institute of Medicine of the National Academy of Sciences has estimated the cost of treating the consequences of CMV infection in the United States at more than $4 billion per year ([2]).

PG36 in the treatment of CMV Infection

Immune compromised mice lethally infected with murine CMV show 100% survival when treated with PG36.  PG36 enhances NK cell activity, prevents the weight loss due to murine CMV infection, and restores splenic mononuclear cell number to the level observed with normal mice.  PG36 also reduces the murine CMV titer in liver, spleen and lung of infected animals.

PG36 prevents death from lethal infection in mice immunocompromised by irradiation.  We hypothesize that it does so by enhancing cytokine production, restoring the suppressed immune system, and enhancing NK cell activity. 

Pathogenic agents that normally produce a transient, subacute infection in normal hosts can have a protracted and sometimes fatal outcome in immunocompromised humans.  In the murine CMV model, which mimics opportunistic infections in immune compromised humans, there is evidence that PG36 is effective in enhancing the recovery of the mammalian immune system from immunosuppressive treatments that enable opportunistic infections to take hold and cause disease.  Murine CMV infection has several features in common with human CMV infection.  In vitro assays using human peripheral blood cells indicate that PG36 enhances the in vitro production by human peripheral blood cells of cytokines important in the anti-viral immune response.  This plant extract has a restorative effect on the radiation-suppressed immune system in mice.  PG36 enhances NK cell activity and prevents death from lethal CMV infection in immunocompromised mice.

Clinical Development of PG36

The strategy for the development of PG36 will be oriented toward potentiation of immune responsivesness, particularly where it has been compromised by viral infection.  Thus, PG36 will be targeted for viral infections in patients at greatest risk of serious complications – patients undergoing solid organ or bone marrow transplantation.  The clinical use could be readily extended to other high-risk groups such as immunocompromised individuals, patients with AIDS and AIDS-related complex, pediatric patients (with underdeveloped immune systems) and individuals suffering from genetic immune insufficiency.  CMV is widely distributed in the human population, with an estimated prevalence ranging from ~40% to nearly 100%, depending upon the method of analysis.  CMV is clearly the most important pathogen affecting transplant patients.  The Institute of Medicine of the National Academy of Sciences has estimated the cost of treating the consequences of CMV infection in the United States at more than $4 billion per year.


[1]  http://www.aic.cuhk.edu.hk/web8/cmv_infection.htm, Web page on CMV Infection – Epidemiology, ICU Web, Dept of Anaesthesia & Intensive Care, The Chinese University of Hong Kong.

[2]  Institute of Medicine Report: “Vaccines for the 21st Century” Institute of Medicine, 1999.

 

 

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