Wednesday, December 2, 2009

The FACTS about Ampligen research in CFS patients

According to the NIH, Poly(I)-poly(C12U), also known as Ampligen, is a type
of antiviral drug called a biological response modifier. These types of
drugs appear to restart human immune defenses against viruses and tumors.
Although there are multiple published studies of Ampligen listed in PubMed,
which is run by the U.S. National Library of Medicine* *National Institutes
of Health, there were only a handful of studies regarding the specific
application of Ampligen in CFS as defined using either the Holmes 1988 or
1994 Fukada definitions. They are listed below:


Ann N Y Acad Sci.<javascript:AL_get(this,%20'jour',%20'Ann%20N%20Y%20Acad%20Sci.');>1993
Jun 23;685:756-7.
RNA drug therapy acting via the 2-5A synthetase/RNase L pathway

Suhadolnik RJ<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Suhadolnik%20RJ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Reichenbach NL<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Reichenbach%20NL%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Hitzges PM<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Hitzges%20PM%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Ablashi DV<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Ablashi%20DV%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Strayer DR<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Strayer%20DR%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Carter WA<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Carter%20WA%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>
.

Department of Biochemistry, Temple University School of Medicine,
Philadelphia, Pennsylvania 19140.

PMID: 8363281 [PubMed - indexed for MEDLINE]


In Vivo. <javascript:AL_get(this,%20'jour',%20'In%20Vivo.');> 1994
Jul-Aug;8(4):599-604.
Changes in the 2-5A synthetase/RNase L antiviral pathway in a controlled
clinical trial with poly(I)-poly(C12U) in chronic fatigue syndrome.

Suhadolnik RJ<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Suhadolnik%20RJ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Reichenbach NL<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Reichenbach%20NL%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Hitzges P<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Hitzges%20P%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Adelson ME<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Adelson%20ME%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Peterson DL<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Peterson%20DL%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Cheney P<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Cheney%20P%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Salvato P<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Salvato%20P%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Thompson C<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Thompson%20C%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Loveless M<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Loveless%20M%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Müller WE<http://www.ncbi.nlm.nih.gov/pubmed?term=%22M%C3%BCller%20WE%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
et al.

Department of Biochemistry, Temple University School of Medicine,
Philadelphia, Pennsylvania 19140.

Latent 2', 5'-oligoadenylate (2-5A) synthetase activity, bioactive 2-5A and
RNase L activity were measured in extracts of peripheral blood mononuclear
cells (PMBC) before and during a randomized, multicenter,
placebo-controlled, double-blind study of poly(I)-poly(C12U) in individuals
with chronic fatigue syndrome (CFS) as defined by the Centers for Disease
Control and Prevention. The mean values for bioactive 2-5A and RNase L
activity were significantly elevated at baseline compared to controls (p <
.0001 and p = .001, respectively). In individuals that presented with
elevated RNase L activity at baseline, therapy with poly(I)-poly(C12U)
resulted in a significant decrease in both bioactive 2-5A and RNase L
activity (p = .09 and p = .005, respectively). Decrease in RNase L activity
in individuals treated with poly(I)-poly(C12U) correlated with cognitive
improvement (p = .007). Poly(I)-poly(C12U) therapy resulted in a significant
decrease in bioactive 2-5A and RNase L activity in agreement with clinical
and neuropsychological improvements (Strayer DR, et al., Clin. Infectious
Dis. 18:588-595, 1994). The results described show that poly(I)-poly(C12U)
is a biologically active drug in CFS.

PMID: 7893988 [PubMed - indexed for MEDLINE]
Clin Infect Dis.<javascript:AL_get(this,%20'jour',%20'Clin%20Infect%20Dis.');>1994
Jan;18 Suppl 1:S96-104.


Upregulation of the 2-5A synthetase/RNase L antiviral pathway associated
with chronic fatigue syndrome.

Suhadolnik RJ<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Suhadolnik%20RJ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Reichenbach NL<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Reichenbach%20NL%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Hitzges P<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Hitzges%20P%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Sobol RW<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Sobol%20RW%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Peterson DL<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Peterson%20DL%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Henry B<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Henry%20B%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Ablashi DV<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Ablashi%20DV%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Müller WE<http://www.ncbi.nlm.nih.gov/pubmed?term=%22M%C3%BCller%20WE%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Schröder HC<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Schr%C3%B6der%20HC%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Carter WA<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Carter%20WA%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
et al.

Department of Biochemistry, Temple University School of Medicine,
Philadelphia, Pennsylvania 19140.

Levels of 2',5'-oligoadenylate (2-5A) synthetase, bioactive 2-5A, and RNase
L were measured in extracts of peripheral blood mononuclear cells (PBMCs)
from 15 individuals with chronic fatigue syndrome (CFS) before and during
therapy with the biological response modifier poly(I).poly(C12U) and were
compared with levels in healthy controls. Patients differed significantly
from controls in having a lower mean basal level of latent 2-5A synthetase
(P < .0001), a higher pretreatment level of bioactive 2-5A (P = .002), and a
higher level of pretherapy RNase L activity (P < .0001). PBMC extracts from
10 persons with CFS had a mean basal level of activated 2-5A synthetase
higher than the corresponding control value (P = .009). All seven pretherapy
PBMC extracts tested were positive for the replication of human herpesvirus
6 (HHV-6). Therapy with poly(I).poly(C12U) resulted in a significant
decrease in HHV-6 activity (P < .01) and in downregulation of the 2-5A
synthetase/RNase L pathway in temporal association with clinical and
neuropsychological improvement. The upregulated 2-5A pathway in CFS before
therapy is consistent with an activated immune state and a role for
persistent viral infection in the pathogenesis of CFS. The response to
therapy suggests direct or indirect antiviral activity of poly(I).poly(C12U)
in this situation.

PMID: 8148461 [PubMed - indexed for MEDLINE]


<javascript:AL_get(this,%20'jour',%20'In%20Vivo.');>

In Vivo. <javascript:AL_get(this,%20'jour',%20'In%20Vivo.');> 1994
Jul-Aug;8(4):587-91.
Ampligen inhibits human herpesvirus-6 in vitro

Ablashi DV<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Ablashi%20DV%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Berneman ZN<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Berneman%20ZN%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Williams M<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Williams%20M%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Strayer DR<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Strayer%20DR%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Kramarsky B<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Kramarsky%20B%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Suhadolnik RJ<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Suhadolnik%20RJ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Reichenbach N<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Reichenbach%20N%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Hiltzges P<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Hiltzges%20P%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Komaroff AL<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Komaroff%20AL%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>
.

National Cancer Institute, Bethesda, MD 20892.

The recently discovered human herpesvirus-6 (HHV-6) is being associated with
an increasing number of conditions in which there is evidence of immunologic
dysfunction. A number of widely available antiviral agents have shown little
or no activity against the virus. We found that Ampligen [Poly (1): Poly
(C12U), a synthetic, mismatched, double-stranded RNA, has potent, previously
unexpected antiviral effects. Cells known to allow replication of HHV-6 were
infected with the virus and treated with Ampligen under various conditions.
When cells were pretreated with Ampligen (concentrations of 100 or 200
micrograms/ml) prior to infection or treated shortly after infection, viral
replication was inhibited by 46-98%. At 100 and 200 micrograms/ml, Ampligen
also inhibited the DNA polymerase activity of HHV-6 by 42-98%. When lower
concentrations of Ampligen (10 and 50 micrograms/ml) were used, only
pretreatment of cells, with Ampligen, followed by virus infection and
carrying the infected cells with Ampligen, significantly inhibited HHV-6
infection (83.7 and 89.1% respectively). Indirect evidence suggests that
Ampligen may inhibit viral attachment to cellular receptors and/or inhibit
intracellular maturation of the virus. The above concentrations of Ampligen
were not toxic to the cells used in the study. Given these in vitro
findings, and the low frequency of toxicity reported with the use of
Ampligen, clinical trials of this drug in patients with evidence of
reactivated HHV-6 infection would seem to be warranted.

PMID: 7893986 [PubMed - indexed for MEDLINE]



<javascript:AL_get(this,%20'jour',%20'Clin%20Infect%20Dis.');>

Clin Infect Dis. 1994 Jan;18 Suppl 1:S88-95.
A controlled clinical trial with a specifically configured RNA drug,
poly(I).poly(C12U), in chronic fatigue syndrome.

Strayer DR<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Strayer%20DR%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Carter WA<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Carter%20WA%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Brodsky I<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Brodsky%20I%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Cheney P<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Cheney%20P%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Peterson D<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Peterson%20D%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Salvato P<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Salvato%20P%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Thompson C<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Thompson%20C%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Loveless M<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Loveless%20M%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Shapiro DE<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Shapiro%20DE%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
Elsasser W<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Elsasser%20W%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
et al.

School of Medicine, Hahnemann University, Philadelphia, Pennsylvania 19102.

Chronic fatigue syndrome (CFS) is a physically debilitating illness
associated with immunologic abnormalities, viral reactivation, and
impairment of cognition. In a randomized, multicenter, placebo-controlled,
double-blind study of 92 patients meeting the CFS case definition of the
Centers for Disease Control and Prevention, the response of several
laboratory and clinical variables to an antiviral and immunomodulatory drug,
poly(I).poly(C12U), was determined. Measures of clinical response included
Karnofsky performance score, a cognition scale derived from a
self-administered instrument assessing symptomatology (SCL-90-R), an
activities of daily living scale, and exercise treadmill performance. After
24 weeks, patients receiving poly(I).poly(C12U) had higher scores for both
global performance and perceived cognition than did patients receiving
placebo. In particular, patients given poly(I).poly(C12U) had increased
Karnofsky performance scores (P < .03), exhibited a greater ability to do
work during exercise treadmill testing (P = .01), displayed an enhanced
capacity to perform the activities of daily living (P < .04), had a reduced
cognitive deficit (P = .05), and required less use of other medications (P <
.05).


Drugs R D. <javascript:AL_get(this,%20'jour',%20'Drugs%20R%20D.');>2004;5(5):297-304.
Mismatched double-stranded RNA: polyI:polyC12U.

[No authors listed]

Ampligen [polyI:polyC12U] is a mismatched double-stranded RNA that acts by
inducing interferon production (immunomodulator) and by activating an
intracellular enzyme (RNase-L) against viral RNA transcripts (antiviral).
Ampligen, currently under development by Hemispherx Biopharma in the US,
acts on the immunological system through T-lymphocyte stimulation and is
indicated for the treatment of chronic fatigue syndrome and acquired
immunodeficiency deficiency syndrome (AIDS), as part of the combined
therapy. Ampligen is available for licensing worldwide. In February 2004,
Fujisawa Deutschland GmbH, a subsidiary of Fujisawa Pharmaceutical Co.,
entered into an option agreement with Hemispherx Biopharma with the intent
of becoming a distributor for Ampligen for the potential treatment of
chronic fatigue syndrome in Germany, Switzerland and Austria. An option fee
of 400,000 euros was paid pursuant to the terms of the option agreement and
upon execution of the Distribution Agreement, Fujisawa will pay Hemispherx
fees and milestone payments with a potential worth of several millions of
dollars. In September 2003, Hemispherx Biopharma Inc. entered into an
agreement with Guangdong Medicine Group Corporation to organise clinical
trials, marketing, sales and distribution for both of its lead compounds,
Ampligen and Alferon N in the People's Republic of China. The agreement
stipulates that the Guangdong Medicine Group Corporation (GMC) will conduct
clinical trials with Ampligen for the treatment of HIV. All costs related to
the trials are to be covered by GMC. Additionally, GMC has to develop and
implement marketing and promotional programmes. In May 2003, Hemispherx
Biopharma and the Center for Cell and Gene Therapy entered into a research
project agreement that will see Ampligen implemented in a protocol used in
patients with relapsed EBV-positive Hodgkin's Lymphoma. In March 2002,
Esteve and Hemispherx Biopharma entered into a collaborative agreement under
which Esteve will be the sole distributor of Ampligen in Spain, Portugal and
Andorra for the treatment of chronic fatigue syndrome. Under this agreement,
in addition to other terms, Esteve will also collaborate in the drug product
development by conducting clinical studies in Spain in patients coinfected
with HIV/HCV. In July 2001 Hemispherx Biopharma announced that it had formed
a strategic alliance with Empire Health Resources for clinical trials of
Ampligen in the treatment of HIV and hepatitis C virus infections. Empire
Health Resources, a healthcare management firm, will be responsible for
accrual and retention of patients for HIV trials, and protocols for trials
in patients with hepatitis C or both HIV and hepatitis C infections.
Hemispherx has entered into a collaboration with RED Laboratories, and RED
Laboratories NV expects that this will facilitate the continued development
of Ampligen. Hemispherx has also entered into an agreement with Schering
Plough to use a Schering facility as its principal manufacturing platform in
the US. This agreement may be expanded to include other territories.
Hemispherx and AOP Orphan Pharmaceuticals have signed a marketing agreement
for Ampligen for the treatment of chronic fatigue syndrome for Austria, the
Czech Republic, Poland and Hungary. In an arrangement between Hemispherx and
Bioclones, Bioclones has certain marketing rights for Ampligen in the
Southern Hemisphere, UK and Ireland.

In the US, Ampligen has been granted orphan drug status for the treatment of
AIDS, renal cell carcinoma (phase II, completed), chronic fatigue syndrome
(phase III) and invasive/metastatic malignant melanoma (phase II). In August
2004, Hemispherx announced that it intends to use the proceeds from the
private placement of company stock to complete the clinical work for its
immunotherapeutics/ antivirals Ampligen and Oragens. Previously, Hemispherx
submitted an application to the EMEA for the approval of Ampligen for the
treatment of chronic fatigue syndrome; the first stage of th;) for the
treatment of chronic fatigue syndrome; the first stage of the regulatory
review has been cleared.

In 2000, Hemispherx Europe (Hemispherx) obtained orphan drug status for
Ampligen for the treatment of chronic fatigue syndrome in the EU, providing
Hemispherx with 10 years of marketing exclusivity following the launch of
the drug, as well as potential financial research benefits for the agent. In
February 2000, Crystaal Corporation (now Biovail Pharmaceuticals Canada)
acquired exclusive marketing rights to Ampligen in Canada, where it
submitted an NDA for the agent for the treatment of chronic fatigue
syndrome. In the meantime, Ampligen has been available since May 1996 under
the Canadian Emergency Drug Release Programme for the treatment of chronic
fatigue syndrome and immune dysfunction syndrome by Rivex Pharma (Helix
BioPharma). Bioclones has initiated clinical studies with Ampligen for the
treatment of chronic fatigue syndrome in Australia. The active substance for
Ampligen is manufactured by F.H. Faulding Ltd. Clinical treatment programmes
for chronic fatigue syndrome in other Pacific Rim countries are planned.
Ampligen is available for severe chronic fatigue syndrome on a named
patient, cost-recovery basis in South Africa. Hemispherx has developed a
'ready-to-use' liquid formulation of the drug and has begun treating
patients with chronic fatigue syndrome in ongoing clinical trials.
Hemispherx has also developed an oral version of the drug (Oragen), which is
undergoing preclinical evaluation.


In February 2001, Hemispherx Biopharma announced that it was initiating
phase II/III trials of Ampligen in the treatment of late-stage,
multidrug-resistant strains of HIV in the European Union. Patients treated
in these studies will have exhausted all other treatment options. In July
2001, Hemispherx stated that Ampligen was being evaluated in a phase IIb
trial in patients with HIV in the US. The trial, comprising two studies,
REARMI and REARMII (Research/Evaluation of Ampligen for Retroviral Mutations
I and II), will evaluate the ability of Ampligen to prevent the emergence of
mutated, drug-resistant strains of the virus. 'Several hundred' patients
currently on antiretroviral therapy and at risk of viral relapse will be
enrolled at centres in Connecticut, New York, Florida and California.

A second phase IIb study evaluating the effect of Ampligen on structured
treatment interruptions (STI) is also underway. Final results from this
study were reported in December 2002. NIH sponsored studies of potential
therapies for SARS have identified Ampligen as having unusually high and
consistent antiviral activity against human coronavirus, the pathogen
implicated as the causative agent of the disease. Ampligen demonstrated very
high potency at very low concentrations (0.4 microg/mL) and had a favourable
safety profile.

In October 2003, Hemispherx announced that, based on these promising new
results, the company will stockpile injectible and/or oral formats of
Ampligen and Alferon N. Independent researchers have demonstrated the
antiviral activity of Ampligen against flaviviruses (West Nile virus, Equine
Encephalitis virus, Dengue fever virus and Japanese Encephalitis virus) as
well as virus classes associated with bioterrorism. In an animal study,
Ampligen was shown to prevent destruction of nerve cells, reduce virus
concentrations in the brain and blood stream and increase survival rates.
Researchers at the Rega Institute in Belgium have published results from an
animal study demonstrating that Ampligen was superior at protecting mice
against coxsackie B3 virus-induced myocarditis compared with pegylated
interferon. In May 2004 Hemispherx announced that it had filed an expanded
US patent application covering the use of Ampligen for the potential
treatment and prevention of severe acute respiratory syndrome (SARS) and
dreaded emerging viruses. Copyright 2004 Adis Data Information BV

PMID: 15357629 [PubMed - indexed for MEDLINE]


<javascript:AL_get(this,%20'jour',%20'In%20Vivo.');>


<javascript:AL_get(this,%20'jour',%20'In%20Vivo.');>

In Vivo. <javascript:AL_get(this,%20'jour',%20'In%20Vivo.');> 2005
Nov-Dec;19(6):1013-21.
Impairments of the 2-5A synthetase/RNase L pathway in chronic fatigue
syndrome.

Nijs J<http://www.ncbi.nlm.nih.gov/pubmed?term=%22Nijs%20J%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>,
De Meirleir K<http://www.ncbi.nlm.nih.gov/pubmed?term=%22De%20Meirleir%20K%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract>
.

Department of Human Physiology, Faculty of Physical Education and
Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium.
Jo.Nijs@vub.ac.be

This paper provides an overview of the evidence addressing the impairments
of the 2'-5' oligoadenylate (2-5 A) synthetase/RNase L pathway in Chronic
Fatigue Syndrome (CFS) patients. The 2-5A synthetase/RNase L pathway in CFS
patients appears to be both up-regulated (i.e. increased levels of bioactive
2-5A synthetase and increased activity of the RNase L enzyme) and
deregulated (elastase and calpain initiate 83 kDa RNase L proteolysis,
generating two major fragments with molecular masses of 37 and 30 kDa,
respectively). The deregulation of the 2-5A synthetase/RNase L pathway in
CFS accompanies decreased NK-function and deregulation of apoptotic
pathways. Since various components of the pathway appear to be related to
performance during a graded exercise stress test, some evidence supportive
of the clinical importance of the impaired pathway in CFS patients has been
provided. Studies addressing the treatment of the deregulation of the 2-5A
synthetase/RNase L pathway in CFS are warranted.
 







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