The Use of RNA to Address Multifactorial Disease

Transcription

1 The Use of RNA to Address Multifactorial Disease Dr. Amy Yasko Dr. Garry Gordon May 2005

2 Many factors influence our susceptibility to disease. These include our stress load, our environment and the toxins we absorb from it, the total number of infectious agents we are exposed to as well as our underlying genetic susceptibility to these diseases. It is important in this day and age to address all the contributing factors to these multifactorial diseases.

3 Multifactorial Disease What do schizophrenia, diabetes and autism have in common? The answer is that many different factors act together to influence their development. As well as fundamentals like age and gender, other genetic and environmental factors may play a role in the onset of these so-called multifactorial diseases. Multifactorial Diseases:Choose your targets BIOPEOPLE, Summer 2004

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5 IOM Report June 15, 2004 In recent years, a number of chronic diseases have been linked, in some cases definitively, to an infectious etiology: peptic ulcer disease with Helicobacter pylori, cervical cancer with several human papillomaviruses, Whipple's disease with Tropheryma whipplei, Lyme arthritis and neuroborreliosis with Borrelia burgdorferi, AIDS with the human immunodeficiency virus, liver cancer and cirrhosis with hepatitis B and C viruses, to name a few. The proven and suspected roles of microbes does not stop with physical ailments; infections are increasingly being examined as associated causes of or possible contributors to a variety of serious, chronic neuropsychiatric disorders and to developmental problems, especially in children.

6 Infectious Agents and Schizophrenia Most cases of schizophrenia are caused by infections and other environmental events occurring in genetically susceptible individuals. Infections relating to schizophrenia occurring in this context would not lead to disease in individuals who do not have the appropriate genetic susceptibility. There was an association between infection with HSV2 and higher rates of schizophrenia. The authors found increased levels of antibodies to Toxoplasma gondii in individuals with recent onset schizophrenia. On a related note: Parasitic infection impairs the immune response to the tetanus vaccine. (Infection and Immunity May 2004 )

7 Multifactorial Disease Environmental Genetic Infectious Stress DISEASE

8 Autism as a Multifactorial Disease Multifactorial Diseases are caused by a combination of factors acting together. This can include infections and environmental events occurring in genetically susceptible individuals. Basic parameters like age and gender, along with other genetic and environmental factors, play a role in the onset of determining vulnerability to these diseases. What we currently call "autism" is actually a medical condition caused by infections and environmental events occurring in genetically susceptible individuals. Infections would only lead to autism if they occur in individuals with the appropriate types of genetic susceptibility that render them vulnerable. The basis for this susceptibility in autism may result from single or multiple mutations in the methylation pathway, combined with complex interactions between thimerosal and this pathway. These imbalances in methylation lay the appropriate groundwork for the further assault of environmental and infectious agents to result in autism. As a result of the decreased activity in the methylation pathway, there is a shortage of methyl groups in the body for a variety of important functions.

9 All of these changes, when they occur in utero or in very young children, can alter brain development, and can also set up metabolic changes that cause ongoing compromise of brain function. The metabolically caused changes in brain function can, however, be treated if problems driving these metabolic changes are treated and corrected. This would suggest that autism is a medical condition associated with a defect in the methylation pathway, with brain and behavior changes that lead to observable autistic behaviors occurring as a downstream consequence of these medical abnormalities. and that it should be characterized as such. Continuing with this analogy, perhaps autism should be reclassified as a defect in methylation that results in neuroinflammatory disease.

10 Atherosclerosis v.s. Autism Genetic MTHFr Infectious Chlamydia pneumonia Streptococcus Stress Inflammatory Mediators Glutamate Improper Calcium Regulation Improper CO 2 Regulation Environmental Cholesterol Cardiovascular Inflammatory Disease Genetic MTHFr Infectious Viral: MMR, Herpes Bacterial Stress Inflammatory Mediators Glutamate Improper Calcium Regulation Improper CO 2 Regulation Environmental Heavy Metals Neuroinflammatory Disease

11 Stress + Infectious agents + Toxins + Underlying genetic susceptibility = Disease

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14 Bacterial infection Antibiotics Lack normal flora Pancreatic malfunction Improper fat absorption Stress Vit K Mg Ca IL6 MAP38 Kinase methylation cell death myelination

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16 MAP38 & Stress

17 How worms tackle stress JNK and p38 pathways are used and integrated in response to pathogen stress in C. elegans By David Secko July 14, 2004 When an animal cell encounters a bacterial or chemical toxin, it needs to respond to ensure its survival, but how it does this is still poorly understood. Now, two independent studies clarify the involvement of the c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signalling pathways in these responses in Caenorhabditis elegans. Both JNK and p38 are well known mediators of stress responses in mammalian cells, and in C. elegans, these proteins, other components involved in their signalling pathways, and their involvement in stress responses are conserved. The two new papers, reported in the July 12 issue of PNAS, together reveal an evolutionarily interconnected mechanism for responding to bacterial stress.

18 Stress MAP38K IL-6 Inflammation

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20 IL6 Inflammation

21 MAP38

22 Inflammation and Stress It is not sufficient to simply address inflammation. It is necessary to also address the underlying physical or chronic stress that leads to further inflammation.

23 Chronic Inflammation is like a house of cards

24 Inflammation

25 Connectivity map of TNF Nature Cell Biology, Feb. 2004, Vol. 6, No. 2

26 Nutrition Industry Executive, Nov/Dec 2002 Andrius Baskys, MD, PhD

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28 Effect of Nerve Calm RNA NutriSwitch on Excitotoxins 26 month old Female Seizure Activity Avg. # Seizures/Day 9/28-10/4 10/5-10/11 10/12-10/18 10/19-10/25 10/26-11/1 11/2-11/8 11/9-11/13 11/13-11/21 11/22-11/29 12/1-12/7 12/8-12/14 12/15-12/22 12/23-12/29 12/30-1/6 1/7-1/13 1/14-1/20 1/21-1/27 1/28-1/31 2/1-2/7 2/8-2/14 2/15-2/21 2/22-2/28 2/29-3/6 3/7-3/13 3/14-3/15 3/16-3/23 3/24-3/31 7/1-7-30

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35 Effect of RNA on Inflammation 57 yr. old Female, A.F., Polymyalgia Rheumatica Initial CRP= 14 Prednisone= 15mg Start Health Foundation & Hyper Immune RNA NutriSwitch CRP=0 Prednisone= 0 mg CRP 3/28/02 4/30/02 5/28/02 6/15/02 7/10/02 8/1/02 8/9/02 8/28/02 10/15/02 11/13/02 12/15/02 1/5/03 4/7/03 5/6/03 6/3/03 11/7/03 1/9/04 3/9/04 8/18/04

36 Glutamate XLead amplifies excitotoxin damage Nerve Calm RNA NutriSwitch Reactive Oxygen Species (ROS) Inflammatory Mediators: COX2 NFKB TNF LO Health Foundation RNA NutriSwitch & Stress Foundation RNA NutriSwitch Metals RNA NutriSwitch & EDTA

37 We are all familiar with the game of telephone where one child whispers a message to the child sitting next to him, who in turn whispers the message to the child sitting next to her, who in turn whispers the message to yet a fourth child and so on until the message has been whispered to the last child in the circle. By the time the message reaches its destination, the final child, it has undergone significant changes.

38 Think of RNA as the mediator that ensures that the initial message is not distorted. RNA helps to facilitate our cell:cell communication by ensuring that the messages in our genes (our DNA) are accurately converted into the structural building blocks for our body (our proteins) in spite of the stresses, the toxins and the infectious diseases in our lives.

39 One area or variable that has been sorely overlooked is enhancing our natural cell: cell communication. As we attempt to facilitate the communication between our cells we can reduce some of our underlying genetic susceptibility to disease.

40 While specific RNAs can help us to address Stress and Inflammation, more importantly they help us to address proper cell cell communication that is necessary to address multifactorial disease.

41 Additional Resources

42 Glutamate and Gaba Neurological Inflammation Virus, Metals, Methylation Austin Conference, November 2004 Phoenix Conference, April 2005 Factors Contributing to Autism Putting It All Together Parents Weekend Boston Conference, August 2004 Genetics of Autism Phoenix Conference, April 2005 Personalized Medicine DVD/ Implications of Genetic Testing Book RNA Boston Conference, August 2004 Phoenix Conference, April 2005

43 Parents chat room