The Stanford Initiative For Chronic Infectious Diseases (including ME/CFS)

December 23, 2010

Posted by Cort Johnson

Dr. Montoya runs the Infectious Disease Clinic at Stanford University. His 50 plus publications have focused on wide range of pathogens including toxoplasma, encephalomyelitis, herpesvirus 6, cytomegalovirus, acanthoamoeba, and many more etc. A preliminary study several years ago suggesting that antiviral therapy returned a large percentage of the recipients to health sent a jolt through the ME/CFS Community. A followup study will soon be released.

He recently sent a letter to his patients and supporters that caught them up to date on his work and his plans for chronic fatigue syndrome and other chronic inflammatory infectious disorders. He is another example of a respected researcher that has made a strong commitment to chronic fatigue syndrome – something we can all be grateful for.

If he’s successful at what he’s attempting to do he’ll achieve one of the great goals of ME/CFS research; he’ll define a group or groups of patients using biomarkers giving them legitimacy and providing them treatments and shepherding them into the embrace of the US medical system. Of course he’ll be doing that under the umbrella of one of the more prestigious Universities in the world.

Below is an overview of the letter; the entire letter is posted below

Dr. Montoya is leading the august Stanford University into areas where many other university’s fear to tread – the chronic infectious diseases such Lyme Disease, (some types of) ME/CFS as well as multiple sclerosis (MS). It appears, though, that his initial work has paid off and has laid the groundwork for growth in the future. Dr. Montoya reports that he has been able to identify several subgroups of patients who’s lives have been ‘dramatically changed’ due to prolonged anti-microbial (antiviral/antibacterial) therapy.

His new initiative aims to investigate the infectious underpinnings of, and provide biomarkers for,a wide array of difficult to understand diseases including ME/CFS, chronic Lyme disease, epilepsy, MS and others.

Recent work - they have recently wrapped up a number of longstanding projects and have or are submitting the results for publication. These include two papers on the double-blinded Valganciclovir trials in EBV and HHV-6 positive ME/CFS patients that started some years ago. Another paper indicating both that clinical (symptoms) and viral titers responded to antiviral treatment in HHV-6 infected patients should be in press in the not too distant future.

(Interlude: Barcelona Conference - According to a report on the internet http://pochoams.blogspot.com/2010/11…-november.html in November Dr. Montoya presented evidence suggesting that monocytes may key a role in this type of ME/CFS patient and that several immune markers (IL5, IL17F, ENA78, EOTAXIN, IP10) improved during treatment – a potential breakthrough in demonstrating the legitimacy of antiviral treatment (and the disorder itself). He has also found that an early antigen marker usually associated with cancer may be a biomarker for this group, that HHV6 integrates into the chromosome of CFS patients, which is apparently not normal for this virus. (Viral integration into the chromosomes means that when the cell replicates the virus replicates as well).

Current Work:

The Big Pathogen Study – They are currently collaborating with Dr. Lipkin and other colleagues on a comprehensive analysis of the pathogens in ME/CFS

Immune Signatures - They are analyzing the immune response using gene expression, cytokine profiles and phosph immune-flow to look for biomarkers and immune signatures correlated with these infections. These biomarkers could be used both to diagnose and to assess improvements during treatment.

Biomarkers in the Brain – Finally? – in a novel approach that reminds one of the attempts to correlated MRI findings with disease early on in the history of CFS, the Montoya team is doing sophisticated new MRI techniques to see if they can use brain imagining to identify unique abnormalities in infected individuals. Several of these pathogens are able to access the central nervous system.

A New Website - a new website explaining their work should be open early next year and a patient forum has been set up.

Quantifying Impairment -Legitimizing ME/CFS - they are also using sub-maximal exercise testing and EEG readings to quantify (and make real) the physical and cognitive impairments in ME/CFS.

Education and Outreach

  • A Major Research Meeting – will be held to change information on and educate investigators on ‘chronic inflammatory diseases.
  • Biennial Education Meeting – will educate researchers, students, etc. on their progress

The Ultimate Goal - is the formation of a Center for Infection Induced Chronic Disease at Stanford, kind of a Stanford Centers Of Excellence for chronic infectious diseases that combines treatment and research. This is a big project that takes much teamwork and over the next five years Dr. Montoya has committed to enrolling and integrating many of Stanford’s best faculty and resources in the project and already has the support of the Director of the Institute for Immunity, Transplantation and Infection, and the Chair of the Department of Medicine.

If you would like more information about any of the projects listed, are interested in participating in any of the research, or would like to financially support a project please contact June Lang at 650-234-0674.

Let the good times roll…

STANFORD UNIVERSITY MEDICAL CENTER

STANFORD UNIVERSITY SCHOOL OF MEDICINE
DEPARTMENT OF MEDICINE
DIVISION OF INFECTIOUS DISEASES & GEOGRAPHIC MEDICINE

TELEPHOl\1E: 650/853-4824
FAX: 650/329-9853
WEBSITE: www.pamf.orglserology
DIVISION OF INFECTIOUS DISEASES & GEOGRAPHIC MEDICIl\1E
300 PASTEUR DRIVE, MlC 5107
STANFORD, CA94301NEWS FROM THE STANFORD INITIATIVE FOR THE
STUDY OF INFECTION-ASSOCIATED CHRONIC DISEASES

FALL / WINTER 2010

Stanford University is taking the lead in a critical area where research is lacking: the study of patients with unexplained chronic illnesses. Chronic Lyme disease (CLD), chronic fatigue syndrome (CFS), and multiple sclerosis (MS) for example, can significantly impair the lives of our patients and result in substantial reductions in previous levels of occupational, educational, social, or personal activities.

Our group has taken a broad-spectrum, innovative approach to discovery surrounding these debilitating diseases. Five years ago our team postulated that infection, or the body’s immune response to it, can play an etiologic role in CLD, CFS and MS. We also hypothesized that prolonged and specific antimicrobial interventions could result in partial or complete reversal of a patient’s symptoms. Since then, we have been able to successfully identify several subgroups of patients whose lives have been dramatically changed with our approach [Kogelnik, 2006]. Our hypothesis has been reinvigorated by the publication last year on the possible association of a relatively unknown infectious agent, namely the Xenotropic murine leukemia virus-related virus (XMRV) [Lombardi, 2009] and the subsequent studies on this virus.

Our proposed initiative for infection-associated chronic diseases will be focusing on chronic Lyme disease, chronic fatigue syndrome, epilepsy, multiple sclerosis, and other unexplained chronic illnesses. We are interested in learning more about the infectious agents that may play an etiologic role in these diseases, including human herpesvirus-6 (HHV-6), retroviruses such as the Xenotropcic murine leukemia virus-related virus (XMRV), parasites such as Toxoplasma gondii, fungi such as Coccidiodes immitis, and bacterial infections such as Borrelia burgdoferi (Lyme).

We hope to see our work changing the lives of patients suffering from CLD and CFS. Our aim is to see patients being validated by their health care providers and fully integrated back into mainstream medicine. We plan to identify biomarkers and other tests that can be diagnostic for these diseases so that appropriate and personalized treatments can finally take place and end individual suffering.

T[B]O DATE WE HAVE MADE PROGRESS IN THE FOLLOWING AREAS:[/B]

Completed Research:
• Last year we completed a randomized, double-blind, placebo-controlled trial on the use of Valganciclovir in patients with chronic fatigue syndrome (CFS)and elevated human herpes virus-6 (HHV-6) and Epstein-Barr Virus(EBV) antibodies. Results from this study are presently being written up and a manuscript will be submitted for publication in December 2010.
• This summer we completed a manuscript using observational data on the response to valganciclovir treatment in Chronic Fatigue Syndrome patients with positive Human Herpes virus 6 and Epstein-Barr virus IgG titers. We are submitting it for publication this month.
• We are also in the process of submitting a manuscript showing that antiviral therapy induces viral and clinical response in patients with central nervous system dysfunction andchromosomally integrated Human Herpes virus 6.

Dissemination of CFS research: Our team frequently presents research findings at national and international meetings. Sharing Stanford’s perspective on pathogens in chronic illness and talking with other physicians who share our interest is important in advancing knowledge and treatment in the entire field of infectious disease.

Formation of an online patient’s support forum: A support forum has been set up on Yahoo groups so Stanford’s CFS patients may interact and give support to each other.

WE ARE CONTINUING OUR IMPORTANT WORK IN THE FOLLOWING AREAS:

Detection of infectious pathogens that may be a trigger for chronic diseases: We are looking for pathogens such as herpes viruses, the Lyme disease agent, xenotropic murine leukemia virus-related virus (XMRV), Toxoplasma gondii, or any unknown pathogen that may be a trigger for chronic diseases such as CFS(chronic fatigue syndrome), CLD (chronic Lyme disease) or other diseases. We plan to look
for such pathogens in a broad population of CFS patients at Stanford and compare the findings to age and sex-matched controls. Towards this end we are collaborating with:

Manisha Desai, Ph.D, Clinical Associate Professor of Medicine
Holden Maecker, Ph.D, Director, Human Immune Monitoring Core, here at Stanford;
and my colleagues at the Columbia University Medical Center in New York City:
W. Ian Lipkin, MD, The John Snow Professor of Epidemiology, and Director,
Center for Infection & Immunity, Professor of Neurology and Pathology
Mady Hornig, MA, MD, Associate Professor of Epidemiology.

Investigation of gene expression and immune system dynamics of infection in acute and chronic diseases: Our team is working on new studies to understand the immune response and possible immune dysfunction observed in our patients. We are looking at gene expression, cytokine profiles, and phospho immunoflow to learn whether our patients’ immune response correlates with the presence of an infectious agent, organism, or pathogen. We hope to identify new markers from the blood that may help predict changes in disease over time and response to changes in medication. Towards these goals we are collaborating closely with the Human Immune Monitoring Core facility at Stanford, including Mark Davis, Ph.D, Professor of Medicine in the Division of Microbiology and Immunology, and Holden Maecker, Ph.D.

Discovery of possible biomarkers in the brain of infection-associated CFS patients: We are collaborating with the Neuroradiology department at Stanford to investigate the rol of novel magnetic resonance imaging (MRI) techniques (e.g. using a 3T magnet) in the hope of discovering biomarkers in the brain for infection-associated CFS.These MRI tests are not available for routine clinical use at this time. Scott Atlas, MD, Professor of Medicine in the Division of Radiology, and his neuroradiology fellows are helping us analyze preliminary imaging data to apply for an NIH grant to begin a larger study on neuroimaging in CFSpatients.

Creation of a Stanford Chronic Fatigue Initiative website: We have been working hard (many thanks to Lindsey Merrihew) to set up a website that will provide patients and their providers with information on Infection Associated Chronic Illnesses. The website should be operational by January. This website should be operational sometime in January. There will be a different web address than the one listed here. We will let you know when that website is operational.

PROJECTS:

Establishment of objective parameters to guantify the physical and cognitive impairments experienced by our patients: Francois Haddad, MD, clinical assistant professor of medicine in the division of cardiovascular medicine, is working with our patients using a sub-maximal effort exercise testing machine to find an objective method to assess fatigue and physical impairment. Marcie Zinn, Ph.D, an
experienced neuropsychologist, will be working with neuropsychological testing and an EEGmachine to find an objective method to quantify cognitive dysfunction in our patients.

Lack of these objective parameters is partially responsible for the skepticism widely prevalent in the medical community towards these patients. We hope that our efforts will result in validated tests that will improve our capacity to diagnose physical and cognitive impairment as well as to evaluate treatment interventions.

Educational outreach: We will host a major research meeting with the participation of international investigators to increase the understanding and the exchange of information in the field of chronic inflammatory disease. A biennial educational meeting aimed at practicing physicians, fellows, residents, and medical students will be initiated. We believe that we can significantly impact the field by re
educating the nascent and established medical community about the major and complex issues faced by our patients.

DREAM PROJECTS:

Formation ofa Center for Infection Induced Chronic Disease at Stanford: We hope, with your financial support, to establish an inpatient center separate from a hospital environment where patients with chronic diseases can benefit from a holistic approach to their treatment. Patients will receive treatment for the specific infectious agents likely to be playing a role in their disease over the course of weeks to months. In addition, they will receive complementary treatments to promote recovery and healing.

MOVING FORWARD:

During the next five years we will mobilize and integrate many of Stanford’s best faculty and resources toward our mission and goals. The director of the Institute for Immunity, Transplantation and Infection, and the Chair of the Department of Medicine have committed to support our mission and have been an integral and key part in the development of this initiative.

The task ahead of us is monumental and requires the participation of faculty and researchers from many areas. Under the leadership of the principal investigator, Jose G. Montoya, MD, we have already begun assembling a world-class team of researchers, post-doctoral fellows, statisticians, bioinformatics faculty, graduate students, laboratory personnel (human immune monitoring core facility), a neuropsychologist, and an exercise physiologist.

If you would like more information about any of the projects listed, are interested in participating in any of the research, or would like to financially support a project please contact June Lang at 650-234-0674.

Relocation of the CFSclinic: The CFSclinic has moved to a new location. Please note that the new address is 900 Blake Wilbur Drive, Palo Alto, CA 94304. Once you are on Pasteur Drive, turn left on Blake Wilbur Drive. The clinic will be on the left, and parking is available in the parking garageon the right. The CFSclinic is located on the second floor. For directions see: http://stanfordhospital.org/directions/maps/BW.html

5 comments

{ 3 comments… read them below or add one }

LJS December 23, 2010 at 6:26 pm

“Formation of an online patient’s support forum: A support forum has been set up on Yahoo groups so Stanford’s CFS patients may interact and give support to each other.”

Does anyone know what the name to this yahoo group is? Also how do we get on their mailing list?

Reply

Cort December 23, 2010 at 6:35 pm
Dr Rod Jones April 7, 2013 at 2:08 pm

Dear Dr Montoya,

You may find this recently published book chapter of relevance to your work http://www.hcaf.biz/2013/CMV_Read.pdf since it investigates the possibility of a new type of infectious immune impairment.

Kind Regards

Rod

Reply

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