Overview of FGF-2 and Autism

The Scientific Logic of Using Homeopathic Recombinant FGF-2 for Autism Augmented with Homeopathic IGF-1, PDGF_BB and TGF_b¹ Growth Factors
by Barbara Brewitt, Ph.D.

FGF-2 has four main activities that are relevant to autism; stem cell stimulation, blood vessel regeneration, bone marrow functioning and intestinal healing.

Introduction to Autism

Autism is a neuro-biological disorder whereby children do not communicate or respond in the same manner as the general population. The incidence of autism is four to five times higher in boys than in girls. Autistic children have developmental delays that impair social interactions, impair verbal and non-verbal communications, such as lack of eye contact, speech difficulties and the openness for social interactions. These children also will enter into repetitive and stereotypical patterns of behavior and appear to have no fear of societal definitions of danger. The ability to identify self from non-self is low. It appears as if the children have low tolerance for frustration, poor comprehension of communications toward them, exhibit poor skin color, reveal little awareness of their surroundings and have a low interest level in their interactions with the world outside of themselves. The sleep disturbance that is most common is early morning arousal (Hering et al. 1999).

The cause of autism is unknown and thus is open to many different types of theories ranging from environment toxicity, to viral infections, and biochemical to developmental imbalances. Seizures and other co-existing nervous system and digestive system imbalances are common. Some children with autism do respond to subtle energy interventions and communications, such as hands-on–healing (Reiki), cranio-sacral therapies, and biofeedback. Some children respond to nutritional interventions and behavioral education. It is entirely probable that autism is not caused by a single agent or can be profiled in the same way, thus the same treatments will not work for every child or to the same degree.

Studies on toxic environmental chemicals show a statistical significance in autistic children and their families (Edelson & Cantor 1998; Felicitti 1981; Niewander and Gordon 1972). Drs. Edelson and Cantor examined 20 autistic children and showed that all children exhibited chronic toxicological damage, especially in the intestines, liver and tissues of the central nervous system.

Brain research is scarce and has enough inconsistencies to prevent a universal conclusion as to the site(s) or causes of autism. However, it is believed that anatomical defects in autism are caused by abnormal development in areas of the brain versus damage to fully developed brains. The areas of the brain that are affected include the cerebellum, the hippocampus and the frontal and temporal lobes of the cerebral cortex, especially those areas related to memory and emotional systems (the limbic system). The abnormalities found include the stunting of dendrites; abnormal secondary and tertiary branching of dendrites and reduced numbers of Purkinje cells.(Arin et al. 1991; Bauman & Kemper 1985).

At the biochemical level of understanding the autistic brain, it appears to be generally agreed upon that serotonin synthesis is depressed in the frontal cortex and the thalamus, while serotonin is elevated in the dentate nucleus of the cerebellum (Buitelaar & Willemsen-Swinkels 2000; Rumsy & Ernst 2000). The neurotransmitters related to dopamine also are implicated as out of balance, especially in the frontal lobes of the cerebrum and the cerebellum (Rumsy & Ernst 2000). In general, damage in the nervous system includes that to dendrites, neurons, axons, myelin and oligodendrocytes. The cerebral cortex controls higher cognitive functions. Connections between the cortex and the basal ganglia control the motor and cognitive programs, whereas connections between the cortex, the amygdala and medial temporal lobes mediate emotional behavior.

There are some theories that autoimmune processes have played a role in the ongoing problems of autism. One study demonstrated that CD4 lymphocytes and their naïve recruit lymphocytes (CD4⁺CD45RA⁺) are very low in autistic children. Natural killer cells are also decreased in autism (Kalf et al. 1982; Pangborn 1984; Warren et al. 1995; Yonk et al. 1990).

A New Perspective

The body is challenged daily by a barrage of toxins and changing pathogens. Our sense of well being and survival are maintained in tact via a highly regulated cell-to-cell communication network within the neuro-immuno-endocrine system. This system uses the language of growth factors (also known as cytokines) to co-ordinate activities of the immune, nervous and hormonal systems. The neuro-immuno-endocrine system is adaptive and memory-specific to each person’s set of experiences. Development and maturation occur as the regulatory controls over cell-to-cell communication strengthen. Premature aging occurs once well-established regulatory controls over cell-to-cell communication break down. It may be possible to strengthen the regulatory controls over cell signaling within the brain, immune and hormonal (endocrine) system in order to improve health, quality of life and build a sense of self in relationship to the surrounding world by using growth factors.

Growth factors are well characterized, biologically active, small proteins that regulate normal cell growth, cell development and cell death. Growth factors are active within the body at very low physiological concentrations that range from nanogram levels (10^-9 molar) and lower. Due to their key physiological roles in growth and development in the body and brain, defects in growth factor regulation are hypothesized to be involved with many diseases.⁴ (Patton et al. 1989). Higher than normal concentrations of growth factors or inappropriately activated growth factors contribute to pathophysiologies via aberrant cell signaling ⁶ (Bellavite & Signorini 1995). Cell signaling molecules, such as fibroblast growth factor-2 (FGF2), insulin-like growth factor-1 (IGF-1) and platelet-derived growth factor (PDGF) are part of the developmental stage growth factors that determine the timing of astrocyte and oligodendrocyte development and provide protective shields for environmental toxins.

I hypothesize that intervention with a combination of these three oral homeopathic growth factors could increase normal brain development and regulate nervous and immune system functioning in autism.

Fibroblast growth factor-2 (FGF2)

FGF2 is a member of a large family of proteins that bind heparan sulfate and modulate the function of a wide variety of cells especially in terms of growth and development, survival, stimulation of new blood vessels (neovascularization) and cell specialization (Nugent & Iozzo 2000; Okada-Ban et al. 2000). It used to be called basic FGF to distinguish it from acidic FGF. FGF2 has been discovered to regulate G-proteins and is well known for its activation of tyrosine (a required rate-limiting precursor amino acid in the formation of serotonin and the synthesis of catecholamines) via adenylate cyclase signaling. There is a direct relationship between FGF2 activity and serotonin uptake activity. FGF2 is widely distributed in the brain, and in the rat (a model with similarities to humans) FGF2 is found at highest levels in astrocytes with FGF2 receptors on oligodendrocytes as well. The hippocampus, amygdala, hypothalamus, mesencephalic trigeminal nucleus and cells of the cerebellum and the lateral walls of the III ventricle in the brain all have both FGF2 and FGF receptors. The nurse cells surrounding the neurons and the white matter have FGF2 and their receptors.

Microinjections of FGF2 in the cerebral ventricles of rat embryos increases the proliferation or cortical progenitors in vivo, resulting in an increased cell number and surface volume (Flora M. Vaccarino and associates at Yale School of Medicine 1995). Research available by Teresa Binstock, a scientist in developmental and behavioral neuroanatomy, points out that FGF2 has four main activities that are relevant to autism; stem cell stimulation, blood vessel regeneration, bone marrow functioning and intestinal healing. Other positive attributes of FGF2 are that it participates in thyroid, thymus and pituitary tissue development. The down side of injectable FGF2 is that it can enhance inflammatory damage in the peripheral tissues and can cause imbalances in astrocyte replication. Too much FGF2 can cause too much stimulation and contribute to gastric ulcers.

Homeopathy as a clinically effective approach to healing

Homeopathy uses drugs that have been highly diluted and shaken to produce safe, less expensive, non-toxic medicines. The most ancient roots of homeopathy date back into the time of the Delphi Oracle (8^th-4^th Centuries B.C.). The roots were represented at this time by the wisdom of the unconscious and the gods’ statement: “That which wounded shall heal”. The medical practice of homeopathy was systematically and formally developed by Samuel Hahnemann, M.D. (1755-1843 A.D.) who stated in the Law of Similars “similia similibus curentur” or “let likes be cured by like”. This Law was developed after years of observing the interactions between drugs and the body. Hahnemann identified two elements underlying the fundamental principle of pharmacology, i.e. a drug has a physiological effect on the body and the body produces positively and negatively reacts to a drug, producing symptoms. A toxic concentration of a drug will evoke the first symptoms of toxicity in the organ(s) where the drug action is most efficacious. Hahnemann found that by serially diluting drugs into homeopathic preparations patients experienced key attributes of the drug without the negative reactions. His writings also clarify that the more powerful the substance, the more dilute it needs to be for therapeutic effectiveness (Hahnemann 1996).

Dr. Hahnemann developed the first systematic method for awakening the ‘elan vital’, or vital energy force within the body and mind. The study of a drug‘s action on a person was called the homeopathic ‘proving’.(1) Typically, a homeopathic drug ‘proving’ included the assessment of a drug’s action on healthy ‘sensitive’ subjects at concentrations high enough to produce or alleviate symptoms. Data collected from self-perceived symptoms on the treatment versus a placebo provided the drug’s guiding symptoms and characteristics.

Other Growth Factors and Nutritional Support for Autism

Insulin-like growth factor-1 (IGF-1)

In addition to FGF2, other important growth factors participate in nervous system healing and protection. IGF-1 is produced throughout the brain, especially in the cerebral cortex, hippocampus, cerebellum and diencephalon (Lee et al. 1999; Ye & D’Ercole 1998). IGF-1 regulates and protects neuronal cell growth, healing and differentiation. It is particularly important during post-natal development even under conditions of under-nutrition. IGF-1 can ameliorate brain growth retardation caused by lack of nutrients or toxic agents. IGF-1 prevents cerebellar granule cells from developing neurotoxicity (Leski et al. 2000). IGF-1 plays critical roles in neuronal survival by regulating which neurons live, die (via apoptosis) or specialize (differentiate). IGF-1 regulates neurite cell length (Raghunath et al. 2000).

IGF-1 is also produced throughout the body with the highest levels produced in the liver (commonly, in response to human growth hormone.). It is also produced in the intestines, kidney, spleen, pancreas, lung, heart, testes, and by macrophage immune cells.

As a widely effective hormone/growth factor/ neuropeptide, IGF-1, generally exerts its effects on growth and healing, especially in the liver, muscles, intestines and in the nervous, immune, and hormonal systems. IGF-1 regulates which cells progress into DNA synthesis. IGF-1 exerts its regulatory effects as a cell-signaling molecule without the necessity of entering the cell through activation of specific, high affinity, cell-surface receptors.

Platelet-derived Growth Factor (PDGF)

PDGF plays a critical role in the timing and differentiation (specialization) of multi-potent stem cells into astrocytes of oligodendrocytes especially during late fetal and post natal development. It plays an important role in regulating FGF activity and is found along the micro-blood vessels in the brain. Its expression is highest in neuronal cell bodies of the cerebellum, cerebral cortex and hippocampus. PDGF stimulates nerve regeneration and glial cell proliferation. PDGF is called the competence factor because it moves cells out of a ‘resting phase’ and activates them to enter the cell cycle. PDGF and IGF-1 work often together to move cells through the entire cell cycle to promote healing, regulate gene expression and maintain optimal homeostasis within the body.

Transforming-Growth Factor-beta 1 (TGF_B1)

TGF_B1 plays a key on/off regulatory role throughout the body turning on and off other growth factor’s effects depending upon the context of the environment surrounding specific cells. TGF_B1 plays a critical role with inflammatory processes, especially with respect to control of genetic regulatory sites associated with gene transcription. TGF_B1 is well known for its participation with wound healing by regulating an ‘off’ signal to prevent overgrowth of cells. TGF_B1 is expressed within the cerebellum, hippocampus, hypothalamus and midbrain (Gayle et al. 1999).

Biomed Comm Inc recommends including homeopathic IGF-1, PDGF and TGF_B1

Homeopathic IGF-1, PDGF and TGF_B1 in combination are recommended as the ‘Optimal Health Trio’. In the body these three growth factors play central roles during the healing processes. We have clinical studies on these products plus one other (granulocyte-macrophage colony stimulating factor) for people with HIV-infection. We found tremendous benefits to the immune and nervous systems, metabolic processes and quality of life. With healthy people, preliminary data collected at UCLA and antidotal evidence shows speedy recovery from inflammatory conditions and ailments that are three times faster than other standard medications.

Nutritional Supports:

From the 1999 Conference for the American College for the Advancement in Medicine held in Orlando Florida nutritional solutions for neuro-degenerative processes were presented. The lectures focused on ALS, Alzheimer’s, Parkinson’s, Autism and Attention Deficit Hyperactivity Disorder.

Among topics on neurotoxicity (Bland 1999) Dr. Jeff Bland presented a case study on a young 6 yr old boy with rigidity. GABA reduces rigidity. If you can’t find homeopathic GABA then try:

500 milligrams of carnitine (3x/day, t.i.d.),

15 mg CoQ10 t.i.d.,

5 mg Vitamin K t.i.d.

Nutrition to protect the nervous system was presented by Dr. Dharma Singh Khalsa (Khalsa 1999). In his book Brain Longevity suggested the following nutrients to maximize brain function while also preventing brain toxicity.:

Vit. E (200 IU or 400 IU with other nutrients),

Co Q₁₀, (100 mg), which helps the mitochondria,

Gingko Biloba (90-120 mg) which helps vasculature,

Phosphadityl serine (100-300 mg) which helps improve attention

Omega 3 oils, or Flax seed, or Fish oil, or DHA

TABLE I – Classic Observable Symptoms of Autism:

How to contact us: 888-637-3516

Customer Support customersupport@biomedcomm.com Ordering information and Review of Symptoms

Barbara Brewitt, Ph.D. - drbrewitt@biomedcomm.com Chief Scientific Officer – Technical Questions

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Raghunath, M., Bannerman, P.R., Lee, C.M., Baker, S., sutton., L.N., Phillips, P.C., Damodar, R.C. A novel kinase, AATYK induces and promotes neuronal differentiation in a human neuroblastoma (SH-SY5Y) cell line. Brain Res. Mol. Brain Res. 2000, 77 (2):151-162

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Endler PC. Schulte J. Ultra High Dilution: Physiology and Physics. Boston: Kluwer Academic Publishers, 1994: IX.

Barbara Brewitt, M.Div., Ph.D.is recognized for her research and publications on homeopathic growth factors and growth hormone for healthy aging, longevity and models of rapid aging such as HIV. Her findings document non-prescription methods for optimizing hormonal, nervous and immune system functioning by integrating three paradigms: growth factor biotechnology, homeopathy and bioelectric medicine. Dr. Brewitt did post-doctoral research on growth factors at the National Institutes of Health (NIH) after receiving a Ph.D. from the University of Washington, School of Medicine, where she is now a Visiting Scientist.