CFS and the antiviral pathwayarticle

Discussion in 'Fibromyalgia Main Forum' started by ravenpaige, Feb 26, 2007.

  1. ravenpaige

    ravenpaige New Member

    Doctors receive $1M grant for HIV prevention research

    Through the use of gene therapy, researchers are striving to find ways to stop the spread of HIV.
    Vicky Thomas
    Issue date: 2/27/07 Section: News
    The Temple News: An editorially independent student newspaper of Temple University, Philadelpia

    Researchers in the School of Medicine are making progress in the understanding and treatment of two diseases caused by abnormalities in the human antiviral pathway: HIV and Chronic Fatigue Syndrome.

    According to the Centers for Disease Control and Prevention, approximately 40,000 people will be infected with HIV this year in the United States alone. The virus' rapid mutation rate allows it to resist many drug therapies, making it impossible for a vaccine to guard the body against the spread of an infection.

    But the research team, headed by Dr. Robert
    J. Suhadolnik, a professor of biochemistry in the School of Medicine, is developing a way to immunize against the spread of HIV through the use of gene therapy.

    After 20 years of researching the intracellular immunization approach to inhibit HIV, Suhadolnik's six-member team was recently awarded a $1 million research grant by the National Institutes of Health to continue its work.

    "We have shown now that we can protect the cell from HIV infection in vitro, in the laboratory," Suhadolnik said. Gene therapy immunization, as opposed to vaccines, introduces an antiviral pathway into a patient's genes. The gene replicates and becomes incorporated into the patient's system.

    When the HIV virus is introduced to the body, the gene becomes active and kills the virus.

    "The HIV virus has developed ways to counteract the natural antiviral pathways," said Suhadolnik, adding that this new therapy could stop the spread of HIV because the delivery of antiviral genes to cells would restore the antiviral defense pathways.

    "Gene therapy is extremely interesting because we're using the body's own immune system to combat the virus without outside chemicals or agents," said Sean Roberts, a graduate student in the School of Medicine and a member of the research team. "It's important towards finding a cure. Our primary goal is to find a cure."

    Suhadolnik said the earlier antiviral construct had shortcomings because there was a chance that the modified cell could contain infectious particles.

    "Now we have a self inactivating vector that we can put the antiviral pathway in by way of gene therapy, and the target cells get activated when the virus comes along," said Suhadolnik.

    He also explained that, like a vaccination, the particles would be inactive until infection was introduced.

    "When you get vaccinated, you don't know that those antibodies are present, but when an infectious particle comes in the body, then the antibodies are made and the disease is wiped out," Suhadolnik said.

    Gene therapy has also been successful in curing other immune deficiency diseases, such as Severe Combined Immunodeficiency or "Bubble Boy" disease, which was once considered a fatal condition.The study of antiviral pathways has been the center of Suhadolnik's research program and is also applied to the team's research on CFS, said Nancy Reichenbach, an associate scientist in the School of Medicine and a member
    of the research team.

    According to Suhadolnik, the cause of CFS is unknown and can occur suddenly with flu-like symptoms and debilitating fatigue.

    The illness, which was once believed to be a psychological disorder connected to depression, is common in women. But Suhadolnik and his research team have found that CFS is not a clinical depression disease, but rather caused by a defect in the antiviral defense pathway.

    While HIV turns off the human antiviral defense mechanism, CFS is a disorder caused when the antiviral pathway is working too hard, making the patient exhausted.

    "Initially we reported that the antiviral pathway was abnormal in patients diagnosed with Chronic Fatigue Syndrome," Suhadolnik said. "In subsequent studies, we reported the appearance of an abnormal protein in the blood cells of the patients diagnosed with CFS.

    "In essence, what we showed was the appearance of a new protein."

    In addition to the grant for their HIV research, Suhadolnik and his team were also granted a U.S. patent for their research and discovery of diagnosis for CFS.

    Vicky Thomas can be reached at

  2. Forebearance

    Forebearance Member

    Wow! Thank you, Ravenpaige!

    I am so grateful for doctors like Bob Suhadolnik, who manage to include CFS research in whatever grant they get.

  3. fight4acure

    fight4acure Member

    Yeah! You found this article I've been looking for since Saturday night when they mentioned it on the news!

    Thanks much!
  4. ulala

    ulala New Member

    What does this mean for us?

    CFS is a disorder caused when the antiviral pathway is working too hard, making the patient exhausted.

    "Initially we reported that the antiviral pathway was abnormal in patients diagnosed with Chronic Fatigue Syndrome," Suhadolnik said. "In subsequent studies, we reported the appearance of an abnormal protein in the blood cells of the patients diagnosed with CFS.

    "In essence, what we showed was the appearance of a new protein."

    Is this new protein causing our antiviral pathway to work too hard? Anyone have any more information?


  5. Forebearance

    Forebearance Member

    Hey, Ulala,

    I believe that when he refers to a "new protein", he is referring to the low molecular weight RnaseL molecule that he discovered. And remember, that is produced when the RnaseL goes crazy and cleaves everything (that it targets) in sight.
    So I think that is what he means by an overactive immune system.

  6. ulala

    ulala New Member

    RNase is a protein. I'd like to see a diagram of the antiviral pathway.

    I found this blurb about CFS on Dr. Suhadolnik's website. It is very technical. He mentions low natural killer cell (NKC) function, but I don't understand exactly what he is saying about the low NKC function. I know that there are things that we can do to raise our NKC, such as low dose naltrexone and mistletoe.

    Maybe some of the more technically inclined people here will know more.

    Best wishes!

    Another major focus of research in Dr. Suhadolnik's laboratory concerns chronic fatigue syndrome (also known as CFS or CFIDS). Chronic fatigue syndrome is an illness of unknown etiology that is associated with sudden onset, flu-like symptoms, debilitating fatigue, low-grade fever, myalgia and neurocognitive dysfunction.

    Dr. Suhadolnik has reported biochemical abnormalities in the 2-5A synthetase/RNase L and PKR antiviral defense mechanisms in peripheral blood mononuclear cells from individuals with CFS.

    These findings are consistent with the reactivation of one or more viruses in individuals with CFS and subsequent dysregulation of the antiviral defense pathways.

    A major research effort in the laboratory focuses on the isolation and characterization of a novel low molecular weight (37-kDa) form of 2-5A-dependent RNase L from CFS peripheral blood mononuclear cells.

    In recent studies, we have demonstrated that the 37-kDa form of RNase L shares structural and functional features with the native 80-kDa RNase L, in particular, at the 2-5A binding and catalytic domains.

    Even though the 80-kDa and the 37-kDa RNase L both bind 2-5A and hydrolyze single-stranded

    RNA in a 2-5A-dependent manner, these two forms of RNase L have different kinetic parameters for 2-5A-dependent activation.

    We have recently reported enzyme kinetic data demonstrating that the rate of RNA hydrolysis by the 37-kDa RNase L is three times faster than that of the 80-kDa RNase L. Continuing characterization of the structural and functional relationship between the 80-kDa and 37-kDa forms of RNase L is designed to provide insight into the role that alterations in the 2-5OAS/RNase L pathway play in the pathogenesis of CFS.

    A recent study examined a number of attributes of clinical presentation, functional status, immune function and the RNase L pathway in a cohort of CFS patients and two well-defined control populations.

    Our results are consistent with the immune activation model of CFS and do not support the contention that CFS is simply a form of depression. The abnormalities demonstrated in the RNase L pathway, i.e., increased 37/80 kDa RNase L ratio, can reliably identify a relatively homogeneous subset of patients within the larger group that comply with the working definition of CFS.

    Observation of an elevated 37/80 kDa RNase L ratio is a quantitative measure that correlates well with the severity of CFS symptoms and with low natural killer (NK) cell function.
  7. bunnyfluff

    bunnyfluff Member

    very good news indeed.
  8. ulala

    ulala New Member

  9. mezombie

    mezombie Member

    NOBEL PRIZE FOR MEDICINE CAN IT HELP US? 10/02/06 05:35 AM (originally posted by Marta608)

    Have you heard about the two U.S. scientists who have won the Nobel Prize for Medicine allowing for RNA interference? If it's true that our illnesses are genetic, this could be the break we've been waiting for. Here's the news story:

    STOCKHOLM (Reuters) - Americans Andrew Fire and Craig Mello won the 2006 Nobel prize for medicine on Monday for their groundbreaking discovery of how to "silence" genes, which has opened up potential new paths to treating disease.

    Fire and Mello's discoveries offer "exciting possibilities" for use in gene technology, said the prize-giving body, the Nobel Assembly of Stockholm's Karolinska Institute.

    "It's amazing. It just hasn't sunk in yet," Mello told Reuters from his home in Massachusetts after learning that he would share the prize of 10 million Swedish crowns ($1.37 million) with Fire.

    Fire, 47, and Mello, 45, showed through experiments with nematode worms that a particular form of ribonucleic acid, or RNA -- the cellular material that transmits genetic information -- can "silence" or switch off targeted genes in a process known as RNA interference (RNAi).

    They published their findings in 1998. This technology has become a hot area of research for pharmaceutical and biotechnology companies, who view it as a promising new way to tackle a range of conditions.

    "I had an inkling that it might be possible, but I am only 45 so I thought it might happen in 10 or 20 years or so," Mello told Reuters, saying the two may give some of the money to charity. The Nobel science prizes are usually given for work done decades earlier.

    The Nobel prizes in medicine, physics, chemistry, literature and peace were established by dynamite inventor Alfred Nobel and have been given out since 1901. Fire and Mello are the first of the 2006 prize winners to be announced.

    Fire told Swedish radio he was very happy.

    "At first it was difficult to believe," he said. He said it was "very nice" to have won and to have "positive attention."

    "I am still the same person, my goals are still fairly simple goals of research and science and teaching and family and I don't expect that to change."

    Fire earned his Phd in biology in 1983 at the Massachusetts Institute of Technology and is now a professor of pathology and genetics at Stanford University School of Medicine. Mello has a Harvard doctorate and is a professor of molecular medicine at the University of Massachusetts Medical School.

    The Massachusetts school said RNAi was now a state-of-the-art method and that a number of companies had bought licenses for the mechanism.

    It mentioned companies including Novartis AG, Bristol-Myers Squibb, Monsanto Co., GlaxoSmithKline and Pfizer had bought licenses, co-owned by the school and the Carnegie Institution, to help in treatment development.

  10. LonelyHearts

    LonelyHearts New Member

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