The Promise of Ampligen
This experimental drug not only stops HHV-6, it helps AIDS and CFS patients function.
First published in: New York Native, issue #663, January 1, 1996
During 1995, a series of extremely disturbing facts were revealed about the damage Human Herpes Virus 6 (HHV-6) is able to inflict. The virus was linked to the brain and nervous system damage seen in Multiple Sclerosis; scientists warned that HHV-6 is a dangerous contaminant of the blood supply, which is not screened for its presence, and is therefore probably being transmitted via transfusion; HHV-6 was found to be the most common infection in AIDS patients, rather than CMV as was previously assumed; it was implicated as a cause of the blinding AIDS retinitis; Italian research linked HHV-6 (Variant A) not only to AIDS and Chronic Fatigue Syndrome, but also to AIDS-associated Kaposi's sarcoma; and, perhaps most importantly, HHV-6 has been shown to be present in the lymph nodes of AIDS patients right from the beginning of their disease.
All of this has resulted in a growing number of scientists who routinely refer to HHV-6 as the "AIDS co-factor."
All of this sounds pretty grim. But there is also good news to report from 1995's scientific endeavors: There is a non-toxic, experimental drug that appears to be able to stop the virus cold in its tracks. The drug is Ampligen, a special form of RNA (the sister molecule to DNA, of which most viruses are composed); it interferes with HHV-6's ability to grow.
The bad news is that the seemingly effective and non-toxic Ampligen, for some impossible-to-understand reason, has yet to be approved by the Food and Drug Administration.
In clinical trials, Ampligen not only inhibits the growth of HHV-6 in tissue culture, but also appears to produce long-term improvement in patients with CFS-who are known to have active HHV-6 infections.
Two recent studies demonstrating Ampligen's effectiveness against HHV-6, performed by some of the leading researchers in the field of the virology of HHV-6 and the clinical treatment of CFS, have added significant ammunition to arguments that Ampligen should be approved by the FDA immediately.
Dharam V. Ablashi was lead author on the scientific report, published in the journal in vivo, which showed that Ampligen inhibited HHV-6 from growing in cells in tissue culture. In addition to other collaborators, well-established CFS researchers Robert Suhadolnik and Anthony Komaroff were investigators in this study.1
Ablashi and colleagues began by pointing out that, while it is believed most people are infected with HHV-6, "many different strains of the virus, comprising of two variants (the A and B variants), with different biologic properties, have been identified." And while HHV-6 has been associated with the generally-mild childhood illness roseola, active HHV-6 infection has also been reported in a number of conditions "known or suspected to be associated with immunological dysfunction." That list, according to Ablashi and colleagues, includes AIDS, Hodgkin's disease (lymphoma), autoimmune disorders like lupus, graft-versus-host disease, and Chronic Fatigue Syndrome.2
HHV-6's possible role in AIDS is particularly troubling, Ablashi and co-workers noted, since, "Like human immunodeficiency virus-1 (HIV-1), HHV-6 is tropic for CD4-positive T-cells; dual infection of CD4-positive cells with both HIV-1 and HHV-6 greatly enhances the rate of CD4-positive cell death." They continued, "Whether the synergistic cytopathic effects of HHV-6 and HIV-1 contributes to pathology or morbidity in HIV infected patients remains to be determined." In other words, does being infected with HHV-6 in addition to HIV indicate a worse prognosis than being infected with HIV alone? The experimental drug Ampligen, Ablashi and colleagues explain, is a mis-matched, double-stranded RNA that has "broad spectrum antiviral and immune modulating activity." They note that when used in combination with "a low dose of AZT," Ampligen "significantly reduced the cytopathic effect inducted by HIV-1" in cell cultures.
As Ablashi recently told the Native, however, giving AZT to an HHV-6 infected individual can, based on laboratory findings, have an extremely deleterious effect, since AZT not only increases the growth of the virus, but increases its cell-killing ability. (See Native #662, December 25, 1995, for the complete Ablashi interview.) Ampligen has also shown a positive effect on the clinical conditions of CFS and AIDS patients, these investigators point out. In particular, a long-term trial of Ampligen treatment of CFS patients resulted in "improved performance on exercise testing as well as improved quality of life, compared to those using a placebo." Therefore, "Since HHV-6 reactivation is frequently seen in CFS infection and since Ampligen treatment seemed to produce a clinical benefit in patients with CFS, we conducted in vitro [laboratory] studies to determine whether Ampligen had antiviral effects against HHV-6."
Cells infected with the GS strain of variant A HHV-6-the type most commonly detected in patients with CFS, AIDS, and other immunocompromised conditions-were treated with Ampligen while being grown in tissue culture, before and after being infected with HHV-6. Cells that were pretreated with Ampligen before infection with HHV-6 showed "substantial inhibition of virus replication, ranging from 45.7-78.3 percent."
A second variation of the experiment was the most successful: When cells were both pre-treated with Ampligen before HHV-6 infection, and then grown in culture with Ampligen present, as well, "inhibition of virus replication was nearly complete," Ablashi and co-workers reported.
In a third variation of the experiment, cells were not pretreated with Ampligen, but treated only at the time of viral infection; no Ampligen was added thereafter to the cultures. Even under these conditions, there was inhibition of viral replication, ranging from 45.7 to 89.1 percent.
The fourth permutation in this series of experiments was the also quite successful: When the cells were not pre-treated but were treated continuously with Ampligen after HHV-6 infection, there was a "dose related inhibition of virus replication, ranging from 95.5-91.3 percent at three different concentrations (50, 100, and 200 micrograms/milliliter)," Ablashi and colleagues report. A concentration of only ten micrograms/milliliter was not enough to inhibit HHV-6 infection, they found.
Perhaps the best news in this study is that inhibition of HHV-6 with Ampligen resulted in absolutely no toxicity to the cells; they remained "90 percent viable," i.e., alive.3 This study indicates that Ampligen appears not only to stop replication of the virus, but also to stop HHV-6 from maturing once it is in the cell.
But do those effects, in the lab, translate into clinical improvement when people with active HHV-6 infections are treated with Ampligen? In 1995, a study was published that showed long-term improvement in patients with Chronic Fatigue Syndrome who were treated with Ampligen. Ablashi was an investigator in this study, as were Ampligen co-inventor William Carter, CFS researchers Daniel Peterson, David R. Strayer, Robert J. Suhadolnik, Sheila Bastien, HHV-6 researcher Berch Henry, and others.4
The answer to the question of whether Ampligen improved the health of CFS patients, who are known to have active HHV-6 infections, was yes. Improvement was noted in patients' Karnofsky Performance Scale (KPS), a measure of ability to perform daily activities like taking care of oneself; memory and IQ improved; exercise tolerance was increased; and there was a measurable reduction of HHV-6 activity.
The Strayer paper reported not only these marked improvements in CFS patients treated with Ampligen, but that they were sustained over the long term.
Fifteen CFS patients, all of whom met the Centers for Disease Control criteria for CFS, participated in the experiment. Their mean age was 44, and 73 percent were women. These patients had been sick for an average of 33 months. "All 15 patients were functionally impaired by their illness as evidenced by their mean baseline Karnofsky Performance Score of 47 (range 20-60)," Strayer and colleagues reported. A KPS score of 100 is considered normally functional. There were two dose regimens administered to the study participants. Initially, they received 200 milligram of Ampligen intravenously twice a week "for variable periods of time"; then, the dosage was increased to 400 milligrams twice a week. Some patients' doses were increased to 400 milligrams three times a week.
Patients were monitored for active Human Herpes Virus 6 infection by blood cultures, which were "observed periodically for the formation of giant cells characteristic of herpesvirus infection," according to Strayer et al. HHV-6 itself was found in those giant cells, and the percentage of those cells infected with Variant A HHV-6 (the GS strain) was determined.
Some patients had more than ten percent "giant cells" in their cultured blood cells, scored as "two"; those with between 0 percent and ten percent scored as "one"; and those with no giant cells scored as "zero."5
No patient in the study dropped out because of toxicity from the drug. At the beginning of Ampligen therapy, patients reported an increase in flu-like symptoms (muscle and headaches), but those symptoms "typically abated" as treatment continued.
"There were no clinically significant alterations of coagulation, blood chemistry values, white blood counts, or liver and renal function test values throughout the course of this study," Strayer and colleagues reported. "Only two adverse events, one case each of feeling lightheaded and facial flushing, were reported as definitely related to Ampligen. There were no severe adverse events attributed to Ampligen." One patient became anemic because of the amount of blood drawn for testing, and was treated with an iron supplement. There were also changes in laboratory blood test values-red blood cell count, hemoglobin, numbers of different types of lymphocytes and platelets-noted during this study. Blood clotting remained normal, as did urinalysis.
Perhaps the most striking improvement was measured by the Karnofsky Performance score (KPS), as Strayer and co-workers explained: "Patients entering the study were significantly incapacitated, with a mean Karnofsky performance score (KPS) of 47. At a KPS level of 40-50 an individual is significantly disabled and requires special care or considerable assistance to perform normal activities of daily living. Self-care is limited and 50 percent or more of the individual's's waking hours are spent confined to bed and/or chair. The average score improved to 67 after 12 weeks of Ampligen therapy. A KPS score of 60-70 describes an individual able to care for most needs with no or only occasional assistance, but unable to carry out any work activities.
"KPS showed sustained improvements through 60 weeks, reaching 80 by 24 weeks and 85 by 60 weeks. An 80 KPS score describes a person capable of normal activity with effort. Some signs and symptoms of disease are still present but no special care is required. The [statistical analysis performed] strongly suggested that the continued increase in KPS during the first 24 weeks of Ampligen therapy was statistically significant."6
Ampligen also reduced the presence of the giant cells indicative of HHV-6 infection. All 14 patients were positive for giant cells before Ampligen treatment. The number of such cells increased during Ampligen treatment in 50 percent of the patients at eight weeks, and in 77 percent at 16 weeks. Four of the patients actually became culture-negative for HHV-6 during Ampligen treatment. In other words: Ampligen stops HHV-6.
In fact, this not-yet-approved, non-toxic drug appears to inhibit the growth of the "AIDS cofactor" completely.
In addition to the other clinical improvements noted during Ampligen treatment, cognitive functioning also increased. Memory scores increased as much as 23 to 45 percent, as did IQ scores.
Only two of the patients in the study failed to experience all of these improvements in clinical status, for unknown reasons. The clinical effects of Ampligen, like its ability to inhibit HHV-6's growth, appeared to be dose-dependent; the most dramatic improvements in daily functioning, Strayer and co-authors point out, occurred after Ampligen dosage was increased to 400 milligrams.
Strayer and colleagues speculate that these clinical improvements could be associated with Ampligen's inhibition of HHV-6.
"Reduced ability to obtain giant cells in short term culture of blood mononuclear cells was noted during Ampligen treatment," they reported. "In eight cases, giant cells were shown to express HHV-6, utilizing specific monoclonal antibodies. This could have resulted from a restoration of normal lymphokine balance, from direct inhibition of virus replication, or from elimination of HHV-6 expressive cells by immune mechanisms. Giant cell formation in this system is associated with HHV-6 infection, but it is not known whether HHV-6 expression or giant cell formation contributes to CFS symptomatology. However, recent studies show that Ampligen can inhibit in vitro replication of HHV-6...."
Why has this seemingly safe, effective drug not been approved by the FDA?
Is it because a treatment that proves effective for both CFS and AIDS would highlight the connection between the two syndromes?References