Autism Questions and Answers

These questions relate to the science behind the preparation, the biological activity of a homeopathic growth factor preparation, and the validation, if any, behind the claims for oral delivery of a growth factor giving benefits to a person with autism. The questions are in bold and the responses from Dr. Brewitt are in regular font.

1. Is there any evidence in the literature that FGF-2 is capable of crossing the blood-brain barrier?

Answer: I am not proposing that molecules of FGF2 cross the blood-brain barrier. We are talking about homeopathy here, not conventional medicine. While conventional science spends a lot of dollars researching biological delivery of a drug to the target site that is not what homeopathy talks about. In fact, many drugs in conventional medicine do not get into the target site. Protease inhibitors don't cross the blood-brain barrier and may not really even get into lymph nodes. So clinical efficacy is not always as clean cut as we 'research scientists' would like it to be.

Homeopathic drugs work via different mechanisms of action than conventional drugs. Certainly, pharmacological effects are thought to occur via growth factor-receptor binding, hence your question about FGF2 crossing the blood-brain barrier. Homeopathic drugs are not thought to literally bind the receptor site. However, that is not to say the FGF2 receptor site is not activated.

There are some published papers demonstrating that electromagnetic types of signals can activate growth factor and hormonal receptor sites. Please see:

1.Bourguignon, G.J., Bourguignon, L.Y. Electrical stimulation of protein and DNA synthesis in human fibroblasts in vitro. FASEB J, 1987 1:398-402

2. Bourguignon, G. J., Jy, W., Bourguignon, L.Y.W. Electric stimulation of human fibroblasts causes an increase in Ca influx and the exposure of additional insulin receptors. J. Cel Phys. 1989, 140 :379-385

3. Liboff, A. R., Rozek, R. J., Sherman, M.L., McLeod, B.R., Smith, S. D., Ca 45 cyclotron resonance in human lymphocytes. 1987 J. Bioelectricity 6:13-32

4. Liboff, A. R. , Williams, Jr., T., Strong, D.M., Wistar Jr. R. Time varying magnetic fields:Effect on DNA synthesis. 1984 Science 223:818-820

5. Liburdy, R., Callahan, D. E., Harland, J., Sloma, T., Yaswen, P. Signal transduction in the lymphocyte is influenced by 60 hz magnetic fields. Mitogen binding, calcium, and mRNA induction. 1992 The Annual Review of Research on Biological Effects of Electric and Magnetic Fields from the Generation, Delivery and Use of Electricity, San Diego, Poster 12

6. Liburdy, R.P. Biological interactions of cellular systems with time-varying magnetic fields. 1992 Ann. NY Acad. Sci. 649:74-95

7. Lin, Goodman, R., Shirley-Henderson, A. Specific region of the c-myc promoter is responsive to electric and magnetic fields. 1994 J. Cell Biochem. 54:281-288

What I hypothesize, after being influenced by the data of the above researchers, is that electromagnetic forces influence cell-to-cell communication which then triggers signal transduction pathways. There is no need for a growth factor to enter a cell. In fact, growth factors do not enter cells in order to affect a change in the cell or neuron, if you will. The cell receptor site only needs to become activated and then change its conformation. I have written about this in Chapter 18 of an in- press book entitled AIDS and Complementary and Alternative Medicine: The Current State of the Science the chapter title is "Bioelectromagnetic Medicine and HIV/AIDS Treatment: Clinical Data and Hypothesis for Mechanism of Action"

2. Microinjections into rat embryos are very different than taking a protein orally. How do you would expect the recombinant protein to promote cell growth? In regards to sample preparation and handling, can’t shaking a sample damage the protein?

Answer: I was asked by parents of autistic children to develop homeopathic FGF2. I questioned why, and this is what they told me. There is a doctor in Mexico, Dr. Aquilar who is taking extracts of purified FGF2 (bovine source?) and injecting it into autistic children. This is scary! However, some children show remarkable progress while some show less or possibly none. Well, homeopathic preparations of recombinant FGF2 would be much safer, much more affordable and potentially even effective!

Let's talk about sample preparations....we scientists all vortex. That is what I'm talking about. FGF2 is always with a buffer of some sort to protect the molecular integrity of the protein during the preparation process. The recombinant protein + buffer is brought up in solution as a source material and then serially diluted and vortexed to provide a homogeneous preparation. This is exactly the way that biochemists and researchers do it.

With respect to taking a protein orally, again you are thinking in biochemical terms. A protein is digested and broken down in the alimentary track into potentially useless or even harmful smaller peptides. In the homeopathic model the homeopathic FGF2 is delivered to the mouth which has been shown as a sublingual or sub-buccal delivery. The mouth, especially the tongue, is filled with lymphatic and blood vessels as well as nerve fibers. The lymphatic system is one of the most permeable structures of the body and signals from growth factors or electro-magnetic sources can evoke lymphocytes to carry signals into the lymph nodes all the way to the axillary and sternal nodes. Lymphocytes have been called the mobile brain, because growth factor signals carried to the immune system also carry signals to the nervous system and the endocrine (hormonal) system. Growth factor signaling is the common language of the neuro-immuno-endocrine system. Thus a signal evoked from oral delivery of a growth factor signal to the tongue can trigger immune signals that emanate to the nervous system. I believe autism is a neuro-immuno-endocrine problem, thus interventions such as homeopathic FGF2 could be highly effective.

3. I'm a biochemist by training, and have had some experience in preparation of proteins samples for X-ray crystallography experiments as a result of my research. It is very critical that a protein be properly folded into its native conformation if you expect it to maintain native function, so I am curious about the expression system being used. If FGF-2 is being expressed in E. Coli, this could be a problem, because to my knowledge this bacteria can't properly process many eukaryotic proteins? Are there any post-translational modifications required for FGF-2's native function such as the formation of disulfide bonds, or glycosylation events?

Answer: FGF2 can be successfully expressed in E.Coli (Sommer, A., et al. 1987, BBRC 144:543-550). Interestingly, FGF2 contains 4 cysteine residues yet reduced FGF2 retains full biological activity, indicating that disulfide bonds are not required for activity. FGF2 stimulates the proliferation of all cells of mesodermal origin as well as neuroectodermal, ectodermal and endodermal origin. FGF2 is chemotactic as well as inductive to neuron differentiation, survival and regeneration.

4. Is there going to be any attempt to study the effects of different dosages of FGF-2 in human patients? Have similar studies (orally administered samples prepared in the same way) been performed in animal models?

Answer: At this time we are manufacturing one formulation, however quite soon will formulate another, also for use by human patients. I am collecting some preliminary assessment information from the parents of autistic children so that I might understand better how to best formulate questions for scientific clinical study.

Biomed Comm^® and I, as clinical investigator, have completed at least 10 different clinical studies on homeopathic growth factors. In three of the studies I was directly involved with patients in the studies conducted in Seattle. In the other seven, there have been clinical investigators in other cities who have conducted the studies. There have also been independent investigators who have verified and reproduced Biomed Comm's^® findings. The most relevant perhaps is our work with homeopathic preparations of recombinant growth factors, IGF-1, PDGF_BB, TGF_b1 and GM-CSF with HIV/AIDS patients. We have 2.5 years of data and many publications about benefits. My publications can be viewed along with excerpts, including background and rationale for homeopathic growth factors and graphs of clinical data from publications, here at this web site.

An article unrelated to homeopathic growth factors, but related to homeopathic medicines and DNA viral infections was published by Singh, L.M., Gupta, G. Antiviral efficacy of homeopathic drugs against animal viruses. Brit. Homeopathic J. 1985, July, 75:168-174.

For human applications, also see Singh, N., Squier, C., Sivek, C. et al. Determinants of nontraditional therapy use in patients with HIV infection. Arch. Intern. Med. 1996, 156:197-201

5. Since the recombinant protein is being administered orally, how would it survive the environment of the stomach and small intestine? I would normally expect that an orally administered protein would be structurally altered by the decreased pH in the stomach, and would most certainly be degraded down by proteases (trypsin, chymotrypsin, etc.) in the gut. I certainly fail to see how FGF-2 would be absorbed by the blood stream intact.

Answer: As I stated earlier, I do not believe that homeopathic medicines work via the traditionally shown mechanisms of actions. While we are talking about recombinant FGF2, the homeopathic preparation and small quantity of substance activates biological effects via a different route. I outline the hypothesis I have through Chapter 18 in the AIDS and Complementary and Atlernative Medicine book, that I cited earlier.

If you reason it out, growth factors and any signaling molecule in the body that activates and regulates feedback loops and cell cycle dynamics is highly powerful. Complex feedback mechanisms are in play that do not follow a linear dose response curve. TGF-beta for example effects cells one way at 10-9th molar and just the opposite way at 10-11th molar.(Battegay, E.J., Raines, E.W., Seifert, R. A., Bowen-Pope, D. F, Ross, R. TGF-beta induces bimodal proliferation of connective tissue cells via complex control of an autocrine PDGF loop, Cell, 1990, 63:515-524).

I’m sure there will be more questions that arise in reading this. If I can be of further assistance please feel free to contact our office at 888-637-3516 or via email at drbrewitt@biomedcomm.com . This is a new area of research, so there is much work to be done. I do not have all the answers, however we are beginning to shed light on biological, physiological and psychological benefits of homeopathic growth hormone and growth factors for humans. These medicines are safe and non-toxic and available to health conscious consumers.

With respect,

Barbara Brewitt, Ph.D.,
Chief Scientific Officer,
www.biomedcomm.com