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Kutapressin is a drug which consists
of processed extract from porcine livers
that contain peptides. Nexco Pharmaceuticals
has introduced a generic form of kutapressin,
called Nexavir, which is based on the
original formula. Kutapressin has
demonstrated efficacy against HHV-6 in a
1994 in-vitro study (Ablashi,
Berneman et al. 1994) as it
inhibited replication by over 90% and has
also been used in the treatment of patients
with herpes zoster. Results of uncontrolled
studies have indicated that treatment with
kutapressin results in the abatement of
symptoms among many patients with CFS.
Kutapressin has also improved the NK cell
function in CFS patients.
Ampligen,is a
mismatched double-stranded RNA with broad
antiviral and immunomodulatory properties
produced by Hemispherx Biopharma, Inc. Hemispherx
recently completed Phase III trials for
Ampligen as a treatment for CFS and is
currently pursuing FDA approval of the
product. In a 1994 study, Ampligen was found
to inhibit replication of HHV-6A in in-vitro
testing at concentrations of 100 and 200
pg/ml (Ablashi, Berneman et al 1994). When
the Ampligen was removed from the
virus-infected cell culture, HHV-6 infection
reappeared slowly but never reached the same
level as before. No toxicity of the cells
was noted. In a 1995 randomized,
double-blinded placebo controlled study (Strayer
et al) of CFS patients, patients on Ampligen
had improved Karnofsky performance scores,
increased capacity for daily living (ADL),
reduced cognitive impairment and improved
work on the treadmill. Patients on Ampligen
also required less medication to control
their symptoms.
In 1994, Sudaholnik evaluated the 2-5A
and RNAase L levels in 15 CFS patients
before and after Ampligen treatment compared
to healthy controls. Patients had lower
levels of 2-5A and increased levels of
RNAase L activity. Therapy with Ampligen
resulted in significant downregulation of
the 2-5A/RNAase L pathway. Also the levels
of HHV-6 replication in PBMCs significantly
decreased after treatment. For additional
information regarding Ampligen, please refer
to:http://www.hemispherx.net/content/rnd/drug_candidates.htm
Whey protein ImmunoPro(which
enhances glutathione production) was found
to inhibit HHV-6 in testing done at Advanced
Biotechnologies (Ablashi et al. unpublished
data). Further, it was found to reduce the
toxicity of foscarnet and potentiate the
foscarnet (thus reducing the amount of dose
administered) when the two were tested
together. Of course, clinical trials are
necessary to determine if there is any
clinical benefit.
Isoprinosine
Isoprinosine is a
synthetic purine derivative licensed in 1971
that exhibits both immune modulating and
antiviral properties. Isoprinosine modulates
T cell and NK function (Diaz-Mitoma et al.,
2003). Isoprinosine did not exhibit side
effects in safety studies or post-marketing
experience (Diaz-Mitoma et al, 2003).
Isoprinosine has been used by physicians
in Europe for CFS patients with evidence of
active HHV-6 infection, although no in vitro
efficacy studies have been done specifically
for HHV-6 infections.
Isoprinosine is not currently available
in the United States.
Immunoglobulin
Study results using intravenous
immunoglobulin (IVIG) for treatment of CFS
have been mixed. Several clinical studies
have been done in patients with CFS
utilizing IVIG compared to placebo. One
double-blind, placebo controlled study of 30
CFS patients (Peterson et al. 1990) did not
demonstrate symptom amelioration or
improvement in functional status. A similar
study of 99 CFS patients from Australia (Vollmet-Conna,
1997) also showed lack of statistically
significant benefit of IVIG compared to
albumen. However, another randomized,
double-blinded study (Lloyd et al., 1990)
comparing monthly high-dose IVIG (2 g/kg)
versus placebo showed improvement as defined
by decrease in symptoms, increased
functional status and improved immunologic
measures. A study of relapsing/remitting MS
patients (Fazekas et al., 1997) compared
IVIG at smaller doses (0.15-0.2 mg/kg) to
placebo. In this 150 patient study benefits
were noted in the IVIG group as measured by
the Kurtzke expanded disability status
score. Over 90% of immunoglobulin batches
tested by Dr. Sudhir Gupta of at University
of California, Irvine contained IgG antibody
to both HHV-6 and EBV at levels sufficient
to inhibit the cell free virus.
While the reasons for the discrepancies
among these studies remains unclear, it is
thought that if humoral immunity is more
important than cell mediated immunity to
control an HHV-6 infection then IVIG would
be a valuable treatment. IVIG is also
expensive and is associated with a variety
of adverse effects.
Interferon:
HHV-6 infection induces production of
certain cytokines from infected macrophages
which play a role in controlling and
containing the viral infection (Inoue et al,
1993). One of these cytokines, Interferon,
has broad antiviral properties and has been
shown to have in vitro activity
against HHV-6 infections.
However there is little information
regarding treatment of HHV-6 with any of the
three types of interferon. Treatment with
alpha interferon has contributed to improved
quality of life scores in CFS patients (See
& Tilles, 1996). Interferon beta has been
used to treat MS patients for over 20 years
as it has shown effectiveness in decreasing
the progression of the disease and reducing
disability (Fillipini, 2003), particularly
with relapsing/remitting MS.
One group demonstrated in vitro that
interferon beta at concentrations of 0.5 ug/ml
reduced the replication of HHV-6 in a line
of T cells. Additionally, they examined the
sera of MS patients treated with interferon
beta compared to control MS patients and
found that the treatment group had reduced
levels of HHV-6 DNA and lower levels of IgM
antibody reactivity. The group also noted
that the sera obtained after treatment
showed decreased levels of HHV-6 DNA as
compared to the pretreatment sera. Another
study (Alvarez-Lafuente, 2004) evaluated 105
patients with relapsing/remitting who were
treated with interferon beta, and compared
them to similar patients who were not
treated and found that the viral load was
twice as high by quantitative PCR in the
untreated patients versus the treated cases.
These effects were only seen during relapse;
no differences were seen when patients were
in remission. Additionally, all cases of
HHV-6 were variant A. Thus, interferon beta
may exert some of the same antiviral
properties exhibited in HHV-6 treatment as
for MS.
Interferon therapy is associated with
several adverse effects including fever,
fatigue, myalgia, nausea, and headache,
among others (Fillipini, 2003)
Transfer factor:
Transfer factor (TF) is a molecule that
can transfer cell-mediated immunity from an
immune donor to a non-immune recipient. TF
seems to have the properties of a cytokine
that can induce an immune response in the
recipient. While TF is antigen specific, it
is not species specific and can thus be
transferred from one species to another
without an allergic reaction in the
recipient. There are several potential
sources of TF; one of the most common is and
accessible is bovine colostrums (Jones,
2003).
Few studies have been published regarding
the efficacy of TF. One study described 28
patients given TF from bovine colostrum with
specific activity for HHV-6 compared to 10
patients who were given TF devoid of
activity for HHV-6. The group given the
HHV-6-specific TF showed significant
improvement in symptom s as well as improved
NK immune function compared to the placebo
group (Fudenberg and Pizza, 1989; Brewer and
Wilson, 2003).
Another report (Ablashi et al, 1996) was
published on the treatment of two CFS
patients with active HHV-6 infections
treated with HHV-6 specific TF. One patient
improved rapidly and resumed normal
activities and the other patient did not
improve. These studies, among others, have
reported no adverse effects from the use of
TF. However, if the patient is lactose
intolerant he or she should not use the TF
from colostrums but find another source of
HHV-6 specific TF, such as human cell line.
While the data for TF in the treatment of
HHV-6 infection is limited, it may be an
attractive option that warrants further
investigation as it has proven to be an
effective therapy in some cases and has a
clean safety record.
Inosine
Inosine is a precursor to adenosine, an
important energy molecule, and plays many
supportive roles in the body. Inosine is a
small molecule that helps restore nerve
function and is one of the few supplements
shown to help regrow nerve connections in
laboratory animals. It is being used in
research and by some physicians for patients
with MS, stroke injury , brain injury and
autism. It is most effective when
administered at the time of injury. It is
used in France and Russia to improve energy
production in the heart.
In 2002, researchers at Harvard's
Children's Hospital, lead by Dr. Larry
Benowitz, began using Inosine to switch
damaged nerve cells in the cerebral cortex
into a growth state. In 2002, they reported
that inosine helped stroke-impaired rats to
regrow nerve connections between brain and
spinal cord and partially recover motor
function. Benowitz's team reported that
inosine could cause nerve cells in rats to
sprout new axons -- the tendrils that nerve
cells reach out to one another with.
The protein, called inosine, acts as a
kind of master switch to turn on a number of
genes involved in the growth of nerve cells,
the team at Boston's Children's Hospital and
Harvard University reports. "Inosine
switches on a whole constellation of genes,"
Dr. Larry Benowitz said.
Benowitz indicated his team found that
inosine can cause severed nerves to
regenerate axons in rats. "It juices them up
nicely," he said, but adding that the
experiment will have to be repeated before
he can be sure it really works the way he
thinks it does.
Benowitz said his team found in the latest
experiment, published in the Journal of
Neuroscience, that inosine passes through
the nerve cell's membrane and activates an
enzyme that in turn controls the cell's
molecular program for axon growth.
"We think it is directly targeting and
activating a protein kinase, an enzyme,
inside the cell, that is the linchpin of the
signaling pathway that activates growth,"
Benowitz said. Inosine promotes the
production of a substance known as 2,3-DPG
that is necessary for the transport of
oxygen molecules from the red blood cells to
body tissues for energy.
In 2004, Dr. Craig Hooper and colleagues
at Thomas Jefferson University,
Philadelphia, administered inosine to 11
people with MS in a study. Among 11 people
taking inosine for 10 or 15 months,
neurological exams showed some clinical
improvement in three patients, and stability
in 8 patients. Some areas of myelin damage
seen on MRI in two patients could not be
detected after treatment (Multiple
Sclerosis, October 2001). Based on these
findings, a larger study is underway at the
University of Pennsylvania, comparing
inosine to placebo in 30 people with
relapsing-remitting MS.
Precaution: Although it has few or no
side effects, inosine is broken down to the
purine end-product, uric acid. Because of
this, inosine supplements should not be used
in people with a history of gouty arthritis,
hyperuricemia or purine autism unless being
monitored by a physician. Pregnant women and
nursing mothers should also avoid its use.
Recommended Dose: 1 capsule
Amount per capsule: Inosine (hypoxanthine
ribose) - 500 mg
Other ingredients: magnesium stearate,
silicon dioxide
Het gebruik van Isoprinosine,
een immuunstimulerend middel, is o.a. getest in
de Scandinavian Isoprinosine-trial bij HIV-patiënten.
2 patiënten in de ISP groep en 17 in de placebo-groep
ontwikkelden AIDS. En bij CVS, met zeer goede
resultaten.
Studie NEJM
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