Deconstructing the Claimed AIDS Cure

Yesterday I reported on a psychiatrist who claims to have a cure for AIDS, but won't explain how it works. Today, I will save him the trouble and tell you how it works. Because I'm nice like that.

The psychiatrist, William Rader, reportedly operates a company -- Medra, Inc -- from his Malibu home. A quick search of the US Patent Application database returns 13 applications filed on behalf of Rader. One of the 13 applications includes the claim -- "A method for treating a patient infected with HIV [..]".

HIV is, of course, a virus. In order for HIV to "work," it has to propagate itself by infecting neighboring immune system cells. In most cases of sexually transmitted HIV strains, the virus spreads by binding to two separate proteins (receptors): CD4 and CCR5. If this strain of the virus can't bind to either receptor, it can't spread or cause harm.

Since proteins are encoded by genes, a slight variation in the genetic sequence can cause the protein to be formed improperly. Humans inherit two copies of the gene -- one from each parent -- so they can have either two normal CCR5 genes, one defective gene (heterologous deficient), or two defective genes (homozygous deficient).

Researchers have found that people who are homozygous deficient for CCR5 are highly resistant, though not impervious, to HIV infection. One potential therapy for those affected by HIV, therefore, is to replace their compromised immune system with one that is homozygous deficient for CCR5 through a stem cell transplant.

This, my friends, is where the story begins. From the patent:

What is claimed is:

1. A method for treating a patient infected with HIV, the method comprising the steps of: administering CCR5-def hematopoietic stem cells to the patient via intravenous injection; and administering CCR5-def neuronal stem cells to the patient via subcutaneous injection.

2. The method of claim 1, wherein administration of the hematopoietic and neuronal stem cells is preceded by aplasia of the patient's marrow.

3. The method of claim 1, wherein about 10 million to about 100 million hematopoietic stem cells and about 10 million to about 80 million neuronal stem cells are administered to the patient. [..]

The patent defines embryonic stem cells as those obtained from an aborted fetus or those obtained from a blastocyst. Rader alleges the cells in his claimed cure come from fetal stem cells, so keep that in mind while reading. T-cells, monocytes, macrophages, and dendritic cells are all immune system cells.

[0038] Another example of the therapeutic use of embryonic stem cells is the use of stem cells containing (or lacking) specific chemokine receptors for the treatment of patients with AIDS. Research into the mechanism of HIV transmission has found that the incidence of transmission of HIV between active sexual partners who are not using any form of prophylactic is greatly reduced when the non-infected sexual partner is homozygous for the genetic marker CCR5. Similar results have been found in CCR5/CCR5(CCR5def) babies born to HIV-infected mothers.

[0039] CCR5 chemokine receptors are G-proteins found in the cell membranes of activated T-cells, monocytes, macrophages and dendritic cells. The receptors not only bind chemokines, but have also been found to act as co-receptors for the binding of immunodeficiency viruses. Macrophage-tropic HIV strains, which infect macrophages more readily than they infect CD4+ T cells, use the CCR5 chemokine receptor on the surface of macrophages in conjunction with the CD4 receptor to enter and infect a cell. Experimental evidence suggests that macrophage-tropic HIV strains establish the HIV infection, while CD4+ T cell-tropic strains are crucial in later stages of the infection. Thus, macrophages defective for CCR5 do not readily bind macrophage-tropic HIV strains, and individuals carrying a homozygous CCR5def mutation are resistant to the initial HIV infection.

[0040] Thus, individuals whose macrophages and T cells are deficient for CCR5 are particularly resistant to infection by HIV. Accordingly, embryonic stem cells found to be CCR5 homozygous deficient are isolated, then are given to a patient via intravenous injection, along with embryonic thymus given in a subcutaneous injection and sheep thymus in a subcutaneous injection. Some portion of the injected embryonic stem cells will differentiate into macrophage and T cells, deficient in CCR5, providing the recipient of the injection with a population of cells resistant to infection by immunodeficiency viruses such as HIV. Optionally, injection of these expanded embryonic stem cells may be preceded by aplasia of the recipient's bone marrow using conventional techniques. The GP41 and the NEF fragment may be important for the inhibition of the polymerase for the virus. It affords the possibility the patient cannot reduplicate the virus (stops viral replication). [..]

EXAMPLE 3

Treatment of a Patient with AIDS using CCR5/CCR5Embryonic Stem Cells

[0074] A 33-year old female living in Europe (Patient X) with late stage AIDS was given a prognosis of only a few days to live. Patient X presented with a sequela of HIV-related infections, including non-Hodgkins lymphoma, Candida albicans, Kaposis sarcoma (in the lung, mouth, skin and vagina), and Trichomonas, as well as hepatic insufficiency, as manifested by elevated liver enzymes, extreme dehydration notwithstanding intravenous administration of saline solution, chronic diarrhea, and extreme weakness. Patient X had a CD4 count of 35, and CD8 count of 586, and a CD4/CD8 ratio of 0.06. (A normal CD4/CD8 ratio is higher than 1.)

[0075] Embryonic stem cells (hematopoietic and neuronal) were isolated from an aborted fetus determined to be homozygous CCR5-def. Approximately 40 million hematopoietic stem cells were diluted with distilled water to 6 cubic centimeters and were given to Patient X via intravenous injection, along with subcutaneous injections of neuronal stem cells (approximately 40 million cells diluted with distilled water to 6 cubic centimeters). Both embryonic human and sheep thymus was also administered. Within six weeks of this treatment, Patient X was free of all HIV-associated infections, her liver enzyme levels had returned to normal, she no longer experienced diarrhea, her strength was close to normal and she was eating normally with a 9 pound weight gain. Her 6-week post-treatment CD4 count was 410, and her CD8 count was 512, resulting in a CD4/CD8 ratio of 0.8.

All-in-all, this looks to be a fairly well thought out (though possibly not original) idea for a therapy. That said, the approach is not perfect.

In the case Rader referenced in the interview, the patient remained HIV positive. The stem cell transplant prevented the HIV from spreading, however, with the inference being that the patient was asymptomatic. Unfortunately, this would probably not prevent the virus from being transmitted to other people through sexual intercourse or blood transfusions.

HIV can also spread using non-CCR5 receptor combinations, including CD4 and CXCR4, as well as CD4 and CCR2. People with homozygous deficiency for CCR5 have been known to be infected by HIV, so the therapy may not work for everyone.

In closing, I want to say that even though all of this sounds really promising, Rader's past history of not allowing others to examine the cells he transplants raises some eyebrows. As an unsatisfied mother of one of Rader's former patient's pointed out, there's no telling what he's really transplanting.

If history is any indication, Rader will not allow his "cure" to be tested for efficacy in clinical trials. Whatever that means, I'll leave for you to decide.