|Non-Technical Summary of How Immudel-gp120 Should Work|
"Changes in the immune system ... will ultimately be the way we control HIV."
- Dr. Gifford S. Leoung, Medical Director of HIV Care at St. Francis Memorial Hospital and Associate Clinical Professor of Medicine, University of California San Francisco.
The Institute for Applied Biomedicine agrees with the increasing numbers of AIDS experts around the world who believe that modifying the immune system is the key to developing new AIDS treatments. Here we summarize our approach and the design of our drug, Immudel-gp120.
HIV and AIDS
AIDS occurs when a person's immune system collapses as a result of HIV infection. The immune system has the challenging task of identifying every kind of foreign invader and removing or destroying it, while recognizing all normal parts of the body and leaving those parts alone. This happens through exquisite cooperation among the different kinds of white blood cells. Among these, the cells that regulate the complex process are called T4 cells (also called helper T cells or CD4 cells). As an HIV infection progresses, T4 cells fail to function properly. Eventually, the number of functional T4 cells decreases until there are too few to run the system. Then, the rest of the immune system must sit idle, no longer able to fight off the many new invaders that would normally pose no threat. So the person becomes ill, and eventually dies, from what are known as opportunistic infections.
In an HIV-positive person, T4 cells fail in two ways. First, T4 cells become infected by HIV. Second, uninfected T4 cells quit functioning and die early. Of these two, the failure of uninfected T4 cells is the most common and the most damaging to the immune system. In fact, in advanced AIDS less than 1% of T4 cells are infected with HIV, but 80% or more of the T4 cells are disabled and destroyed. (See Direct Infection Model)
Current Anti-Viral Drugs
Current AIDS treatments are designed to destroy HIV's ability to reproduce. While these treatments do an excellent job at preventing more T4 cells from becoming infected, they do little to prevent the failure of uninfected T4 cells. Anti-viral drugs have been very effective for some, but not at all effective for others. Even when the drugs are initially effective, they have dangerous side effects, are prone to drug resistance, and are not affordable or practical for most HIV-positive people. (See Current Treatments)
Another Approach to AIDS Treatment
We have developed and filed for patent protection on a drug, Immudel-gp120, which should destroy HIV's ability to cause damage to uninfected T4 cells, rather than target HIV itself. The drug's design is based on extensive and varied research evidence indicating that HIV confuses the immune system into attacking its own T4 cells. (See Literature Excerpts or References.) This explains how HIV does so much damage even to cells it does not directly infect. The following summarizes how HIV confuses the body and how Immudel-gp120 would prevent the body from attacking itself.
The Protein gp120 from HIV Sticks to T4 Cells
The surfaces of HIV and cells infected with HIV are covered with protein molecules called gp120. They are not attached very securely, and fall off in large numbers to float through the bloodstream. When free-floating gp120 molecules bump into a T4 cell, they stick to receptors on the T4 cell surface. But gp120 alone does not harm the T4 cells if the person is given a common hormone supplement.
B Cells Make Antibodies to gp120
The combination of HIV and gp120 does not, by itself, cause serious problems in the immune system. Those problems come with the addition of antibodies against gp120. These antibodies are made by B cells, another part of the immune system. B cells make antibodies against foreign molecules. Antibodies are designed to stick to the foreign molecules and anything attached to them and label them as foreign so that other parts of the immune system can destroy them. Since gp120 is foreign, a small fraction of the B cells make antibodies to gp120. These antibodies go out into the blood stream and attach to gp120 proteins wherever they find them.
These Antibodies Bind to gp120 on T4 Cells, Inactivating the T4 Cells
Unfortunately, when an antibody attaches to a pair of gp120s that are stuck on a T4 cell, the T4 cell is irreversibly inactivated and marked for destruction. These T4 cells are not infected by the virus, but are damaged and destroyed by the combination of gp120 and antibody to gp120. (See Autoimmune Model.) This combination causes antibodies to indirectly target T4 cells.
For example, experiments using mice which have human immune system cells show that if you inject these mice with gp120 and antibody to gp120, their T4 cell count drops and they develop the symptoms of AIDS, even though they are not infected with HIV.
Immudel-gp120 Prevents the Production of Antibodies to gp120
Thus, when the body produces anti-gp120 antibodies to attack gp120 and HIV, the antibodies also attack gp120 stuck to T4 cells, and accidentally damage the T4 cells themselves.
Autoimmune Model Diagram
There are two ways to end this process. First, reduce or eliminate the production of gp120 as current, failing, drugs do to some extent. Second, reduce the production of antibody. Our drug, Immudel-gp120, is designed to get rid of the small fraction (6%) of the B cells that make antibodies to gp120. Without those particular B cells there will be no antibodies to gp120, and so the body will no longer target itself.
Immudel-gp120 consists of two parts joined together. The first part is gp120, modified so that it cannot bind to T4 cells, but binds only to those B cells that make antibodies to gp120. The second part is a protein that kills any cell it can get into, but changed so that it has no way to get into a cell on its own. The only way the protein can get into a cell is by being carried into one by the gp120 to which it is attached. And the only cells the gp120 can get into are the particular B cells we want to eliminate.
So, B cells which are sensitive to gp120 pick up the gp120 portion of Immudel-gp120, drag the entire drug into themselves, and are then destroyed by the toxin portion of the drug. Consequently, these B cells are no longer present to make antibodies to gp120. With no antibodies being produced, antibody-targeting and destruction of uninfected T4 cells will end.
We have demonstrated that Immudel-gp120 is effective at stopping the production of antibodies to gp120 (see Pilot Test Results). Since the body is always making more B cells, a person on this drug will have to have one injection of Immudel-gp120 each month for life.
Immudel-gp120 Should Prevent AIDS in HIV-Positive People
Immudel-gp120 should keep an HIV infection in remission indefinitely and restore people with full-blown AIDS to normal immune function. While a person on this drug would still be HIV-positive, he or she should be able to live out a normal life span with a fully functional immune system. Immudel-gp120 does not work on the virus itself, and therefore would not be vulnerable to the rapid development of drug-resistant strains of HIV. And Immudel-gp120 should be inexpensive to make because it will be produced by a substantially cheaper process than the current anti-viral drugs.
We predict that, like a similar drug in use for leukemia, Immudel-gp120 would have very few side effects (see Anticipated Side Effects in Humans). Safety testing of Immudel-gp120 in rats and human cells demonstrated no observable side effects (see Pilot Test Results).
We have filed for patent protection on Immudel-gp120. Please see Technical Information or Contact Us if you would like more information, the research evidence which supports our claims, or answers to any other questions you might have. Our unique research is supported by grants and charitable contributions. We can only succeed if you and others Support Our Research.
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