Aethlon Medical is pioneering the development of viral
filtration devices to treat HIV/AIDS, Hepatitis-C (HCV), and pathogens that
are mass casualty biological warfare candidates. Each treatment application
employs the use of a proprietary technology known as the Hemopurifier™,
which is designed to rapidly reduce the presence of infectious disease and
toxins in the body. The Hemopurifier™ converges the established scientific
principals of affinity chromatography and hemodialysis as a means to augment
the immune response of clearing viruses and toxins from the blood before
cell and organ infection can occur. Aethlon has an experienced management
team, which receives support and guidance from globally recognized science
advisors representing the infectious disease, biowarfare, and dialysis
industries.
Published HIV/AIDS & HCV Data
Aethlon’s science publications document that on average,
the HIV-Hemopurifier removes 55% of HIV from human blood in three hours, and
in excess of 85% in twelve hours. The HIV-Hemopurifier also cleared 90% of
the toxic protein gp-120 in one hour. GP-120 is known for depleting healthy
immune cells, which is the hallmark of AIDS. The HCV-Hemopurifier removed
58% of the Hepatitis-C virus from infected blood in two hours. The HIV & HCV
Hemopurifier are both designed to extend the benefit of drug therapies by
capturing mutant viral strains that cause drug resistance, and to enhance
and prolong life for infected patients who inevitably become resistant to
drug regimens.
Countermeasures Against Bioterrorism
Aethlon recently announced that it is developing
treatments to combat infectious agents used in biological warfare and
terrorism. These Hemopurifiers are designed for rapid deployment by American
armed forces as wearable post-exposure treatments on the battlefield, as
well as a dialysis based treatments for civilian populations. Aethlon is
focusing its biodefense strategy on "Category A" agents that are considered
by the Centers for Disease Control (CDC) to be the worst bioterror threats.
These agents include the viruses that cause Smallpox, hemorrhagic fevers
such as Ebola and Marburg, the Anthrax bacteria, and Botulinum toxin. In
addition to these pathogens, Aethlon is uniquely suited to treat unknown new
toxins or hybrid pathogen strains. The most frightening forms of these
infectious diseases will genetically engineered biological weapons designed
to kill large population masses.
Aethlon’s biowarfare treatments are based on the same
proprietary Hemopurifier™ filtration technology that is utilized in
advancing the Company’s HIV/AIDS, and Hepatitis-C treatments. The regulatory
path for Aethlon’s biowarfare treatments will be pursuant to a recent rule
implemented by the U.S. Food and Drug Administration for medical
countermeasures to weapons of mass destruction. Under this rule, in
situations where it is deemed unethical to conduct efficacy studies in
humans, a treatment can be reviewed for approval on the basis of efficacy in
the most relevant animal species and safety data in humans. On March 4,
2004, Aethlon announced a cooperative agreement with the National Center for
Biodefense (NCBD) at George Mason University. Under the agreement, Aethlon
and the NCBD will collaborate to develop pathogen and toxin filtration
devices designed to protect the lives of U.S. Military personnel exposed to
infectious agents as a result of biological warfare.
A Technical Summary of the Hemopurifier™
The basis for Aethlon’s technology is the extracorporeal
removal of toxins and pathogens from the blood using modified hollow-fiber
hemodialysis cartridges that selectively trap targeted toxins and pathogens.
The derivation of the technique, which is more accurately known as affinity
hemodialysis, is the combination of affinity chromatography, developed by
Cuatracasas, Wilchek and Anfinsen [1] in the late 1960s, and hemodialysis, a
proven technique that has been used clinically for over 30 years to treat
renal failure.
Hemodialysis removes urea and other small metabolic
toxins that build up in the blood of patients with acute or chronic kidney
failure. Acute renal failure is generally handled in the intensive care unit
using continuous renal replacement therapy (CRRT) while chronic renal
failure is treated using intermittent hemodialysis (IHD) in a stand-alone
dialysis clinic.
While there are several variations of technique, a
catheter is most often the primary method utilized to gain access to the
blood, which is then pumped through a hollow-fiber hemodialysis cartridge.
Within the cartridge, toxic salts, urea and excess water pass through small
pores in the walls of the hollow-fibers and are removed. Proteins and blood
cells that are too large to pass through the membrane are retained. The
purified blood is then returned back into circulation.
Renal hemodialysis, as practiced today, has technical
limitations due to the specifications of the membranes that make up the
dialysis cartridge. This technology is not applicable to a wide array of
toxins and pathogens because the hemodialysis cartridges are only capable of
non-selectively removing substances of a particular size from the blood.
Thus, in addition to removing toxins, the dialyzer may also remove
substances that would be preferential to retain. Additionally, many toxins
are too large to pass through the dialysis membranes and are therefore not
removed even when it would be desirable to do so.
Aethlon substantially increases the binding or clearance
capabilities of traditional dialysis by designing a cartridge which has
pores large enough to allow large toxins and even whole viral particles to
diffuse through fiber walls, yet the cartridge is selective enough to remove
only the targeted particles [2]. Materials such as antibodies, which bind
only to their corresponding antigen, provide selectivity, while the use of a
sealed cartridge allows for the use of large pore hollow-fibers, which are
traditionally incompatible with renal dialysis.
The binding antibodies or other selective agents are
chemically bound to the surface of glass or plastic beads that surround the
outside of the hollow-fibers. This design helps to prevent active materials
from entering the bloodstream while virus particles and toxins diffuse
through the hollow-fiber pores and are captured by the immobilized antibody.
As a result, relatively large pathogenic or toxic particles can be
selectively bound within the cartridge, while non-toxic materials of similar
size can readily leave and re-enter the bloodstream. Blood cells and
platelets, which are too large to enter the membrane, remain in the
hollow-fiber and are returned to the patient. Another advantage of the
Hemopurifier cartridge is the reality that it does not require the
development of any new equipment. Each cartridge has been designed so that
it fits directly onto the global infrastructure of dialysis machines already
located in hospitals and clinics.
Treatment for Infectious Viruses
Current treatment options for viral illnesses include
vaccination and antiviral drugs. Vaccines have been very successful in the
prevention of viral diseases (e.g. polio and smallpox). Unfortunately, newly
emerging pathogens (e.g. SARS, Nipah), highly mutable RNA viruses (e.g. HIV
and Hepatitis C virus) and exotic viruses that might be used in terrorist
attacks often do not have vaccine treatments. Similarly, antiviral drugs can
be useful in controlling viral infections, however, there are no general,
broad-spectrum, antiviral agents capable of treating the vast array of
potential viral infections. Additionally, many viruses are capable of
rapidly developing drug resistant mutations. Moreover, it generally takes
many years and hundreds of millions of dollars to develop vaccine and drug
candidates that may or may not be approved for use by the FDA.
Aethlon’s Hemopurifier represents a new approach in the
treatment of incurable viral diseases. This therapy is designed to work in
conjunction with current regimens to remove infectious viral particles,
toxic viral proteins, deleterious cytokines, and other harmful immunological
mediators directly from the blood of the patient. By removing circulating
virus and other toxins from blood, the Hemopurifier cartridge prevents virus
from entering unaffected tissues and cells, thereby allowing the body’s
natural defenses a chance to recover and reject the disease.
Current treatment targets include HIV/AIDS and Hepatitis
C virus, both of which are highly mutable RNA viruses that cause diseases
for which no adequate cure exists. In preclinical studies of HIV infected
human blood, Aethlon has demonstrated that the Hemopurifier can remove up to
90% of the viral toxin, gp120, in a 1 hour treatment along with 25% of the
circulating HIV-1 virus [3, 4]. The longer the treatment, the more virus and
viral toxins are removed.
Biodefense and Newly Emerging Pathogens
Viral and bacterial illnesses have always been with us
and have sometimes been used as biological weapons. In recent times, some
nations have refined and weaponized various pathogens for use in biowarfare
[5]. While there are differences between bioweapons grade organisms in the
way they are transmitted or how they are designed to kill, nearly all
related viral infections will result in sepsis.
Sepsis is essentially a dysregulation of the immune
system, often described as a “cytokine storm” or septic shock [6, 7].
Microbial invasion sets off an immunological chain reaction mediated by
inflammatory proteins produced by cells and tissues. Overexpression of these
immunological mediators “confuses” the immune system, ultimately resulting
in major organ failure and death. Hemodialysis has been used for many years
as a treatment in septic shock and has generally been acknowledged to be
beneficial [7]. Unfortunately, the current technique is limited in the size
of the toxins that can be removed and is inherently non-selective,
restricting the procedure’s efficacy [6].
Aethlon’s Hemopurifier is designed to solve many of these
issues. The Hemopurifier is capable of selectively targeting specific immune
mediators responsible for shock, thereby returning the signaling system to
normal levels. At the same time, the Hemopurifier can remove whole virus,
viral and bacterial fragments and toxic proteins that are too large to be
removed by standard hemodialysis. Thus the Hemopurifier adds the capability
of removing the antigens that are responsible for generating immune mediator
production in the first place, effectively removing the source of the
problem.
Perhaps just as important is the speed with which new
treatment options can be developed. A new bioweapon or emerging pathogen is
unlikely to have an effective treatment. For example, typical biowarfare
pathogens have been “weaponized,” or genetically engineered to contain genes
that can make them resistant to available drugs and vaccines. This presents
a substantial barrier to treatment since the development of new drugs or
vaccines usually takes several years (e.g. the long sought AIDS vaccine
[8]).
However, a Hemopurifier targeted to the new pathogen can
often be constructed in a matter of a few months. All that is required is
the existence of an antibody or binding protein that selectively adheres to
the surface of the pathogen or toxin. In one recent case, Aethlon built and
tested a new antibody cartridge for both HIV and HCV removal from infected
blood in less than 10 days. With the existence of an animal model and
samples of the virus, animal trials can be performed and a new Hemopurifier
treatment for the corresponding biowarfare pathogen could be submitted for
market clearance discussions with regulatory authorities within months.
References:
1. Cuatracasas, P., Wilchek, M. and Anfinsen, C.B.
Selective enzyme purification by affinity chromatography. Proc Natl Acad
Sci USA, 1968. 61(2): p. 636-43.
2. Tullis, R., Scammura, D. and Ambrus, J. Affinity
Hemodialysis for Antiviral Therapy with Specific Application to HIV. J
Theor Med, 2002. 3: p. 157-166.
3. Tullis, R.H., Duffin, R.P., Zech, M. and Ambrus, J.L.,
Jr. Affinity hemodialysis for antiviral therapy. I. Removal of HIV-1 from
cell culture supernatants, plasma, and blood. Ther Apher, 2002. 6(3): p.
213-20.
4. Tullis, R.H., Duffin, R.P., Zech, M. and Ambrus, J.L.
Affinity Hemodialysis for Antiviral Therapy. II. Removal of HIV-1 Viral
Proteins from Cell Culture Supernatants and Whole Blood. Blood Purif,
2003. 21(1): p. 58-63.
5. Alibek, K. and Haldelman, S. Biohazard:The Chilling
True Story of the Largest Covert Biological Weapons Program in the
World-Told from Inside by the Man Who Ran It. 1999, New York, NY: Random
House, Inc.
6. Reiter, K., Bellomo, R., Ronco, C. and Kellum, J.A.
Pro/con clinical debate: is high-volume hemofiltration beneficial in the
treatment of septic shock? Crit Care, 2002. 6(1): p. 18-21.
7. Kellum, J.A. and Bellomo, R. Hemofiltration in
sepsis: where do we go from here? Crit Care, 2000. 4(2): p. 69-71.
8. Cohen, J. A shot in the dark. The wayward search for
an AIDS vaccine. 2000.
