Monday, February 6, 2012

6 Viral Genetics Issues Latest Report On Chronic Lyme Clinical Trials Status

Recently, Viral Genetics posted an update on its move towards testing its product, VGV-L, for treating chronic Lyme disease.

Research for this product was funded by two Lyme disease advocacy organizations, Time For Lyme, Inc. and the Turn The Corner Foundation.

You might be familiar with the project lead, Dr. Karen Newell Rogers, whose research was mentioned at the LDA-Columbia University Lyme 2011 Lyme and TBD Conference.

I previously wrote about Dr. Newell Rogers research, and highlighted the following excerpt from a summary report on her conference presentation:
"Dr. Karen Newell Rogers presented a talk about novel ways to target chronic inflammation and chronic immune activation among patients with chronic Lyme disease. 
She pointed out: 
"[...]Some researchers would argue that chronic inflammation requires the continuous presence of bacteria, whereas others would suggest that continuous presence of bacteria does not always result in inflammation and that exacerbations of chronic symptoms could result from infection with a different organism--or that chronic symptoms could re-cur from unrelated pro-inflammatory events. Potentially reconciling these seemingly conflicting perspectives on the mechanism of Lyme disease may be the effect of Borrelia burgdoreri’s bacterial by-products on Toll Like Receptors, (TLR)-mediated immune activation. 
TLR appear to be the “gate-keepers” of an inflammatory response. Bacteria, including Borrelia, produce products that, by binding to TLRs on the cell surface, promote leukocyte activation, cytokine production, and acute inflammation. In some genetic backgrounds of mice, acute inflammation is sufficient to fight off infection and resolve disease. In other mouse strains, the pathogens, or in this case the bacteria, get past TLR-induced inflammation and remain symptomatically undetectable in cells and tissues (Barthold, etc); Barthold et al. have found that no matter how severe or mild the disease in any of the genetically inbred strains of mice, there was no more inflammatory disease when the bacteria were eliminated."
So what is VGV-L, and what does this soon-to-be-tested product supposedly do? It would seem to fall more in line with Dr. Newell Rogers' research addressing chronic inflammation than addressing chronic infection, based on what I've read thus far.

According to Viral Genetics' web site, VGV-L seems to be related to Targeted Peptide Therapy (TPT), a therapy which uses synthetic peptides to "trick" cells that may be responsible for harmful symptoms and makes these cells vulnerable to the body's natural immune response mechanism.

What exactly are targeted peptides? According to Viral Genetics (VG), targeted peptides are custom-designed protein fragments that work to modify certain immune system reactions that they believe cause or worsen some inflammatory diseases.

More about Targeted Peptide Therapy is found on its own VG page:
 "Autoimmune diseases occur when the body reacts to itself or self-tissues. In some cases, an external threat from disease-causing organisms activates too many of certain types of immune cells which in turn cause damage the body. A physical trait of those cells also makes them impervious to the body's natural defense system that would ordinarily limit their numbers.  
TPT works by tricking those impervious cells into dropping their defenses. They can be fooled into releasing their protective shields, swapping the shield for a synthetic TPT-polypeptide instead. Those peptides, created by our research team, have been engineered to make the cell susceptible to the body's natural defenses. We expect our TPT drug compounds to enable the body to destroy the cells that help trigger the symptoms of autoimmune diseases." 
 So what this sounds like is it a treatment for chronic Lyme disease which lessens inflammation by modifying the immune system in some way.

And judging from the content above, I am wondering if the "certain types of immune cells" of which there are too many could be referring to the overabundant low quality plasma cells that were found in lymph nodes in Tunev and Barthold's study, "Lymphadenopathy during Lyme borreliosis is caused by spirochete migration-induced specific B cell activation."?

So what is the status of getting VGV-L's TPT to the clinical trial stage?

Excerpts from its letter to shareholders indicated that due to the time required for coordinating schedules, screening clinicians, and presenting the data, that it was only "recently that we neared finalization of securing a clinician to act as lead on this program. We expect to be able to discuss this in much more detail very soon, but I am very confident that we will be filing our pre-IND for our Lyme disease candidate this year."

 For those who are reading along who do not know what a pre-IND is, "IND" stands for Investigational New Drug, and any clinician who wishes to begin clinical trials to test a new drug must file for approval from the FDA.

From the FDA's own site:
"During a new drug's early preclinical development, the sponsor's primary goal is to determine if the product is reasonably safe for initial use in humans, and if the compound exhibits pharmacological activity that justifies commercial development. When a product is identified as a viable candidate for further development, the sponsor then focuses on collecting the data and information necessary to establish that the product will not expose humans to unreasonable risks when used in limited, early-stage clinical studies.

FDA's role in the development of a new drug begins when the drug's sponsor (usually the manufacturer or potential marketer) having screened the new molecule for pharmacological activity and acute toxicity potential in animals, wants to test its diagnostic or therapeutic potential in humans. At that point, the molecule changes in legal status under the Federal Food, Drug, and Cosmetic Act and becomes a new drug subject to specific requirements of the drug regulatory system."
(For more specifics, see: http://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/investigationalnewdrugindapplication/default.htm)

I am finding this all very interesting and will continue to watch Viral Genetics as they move towards the trial phase.

I wonder what requirements will need to be met for study participants - and how many chronic Lyme disease patients would be willing to sign up?

Would you?

Additional Information: http://www.viralgenetics.com/investors/2012-Letter-to-Shareholders.pdf


6 comments:

  1. I noticed the announcement contained in the Viral Genetics website just a day or two ago, and despite a bit of digging, wasn't able to find more details about the new drug. This probably shouldn't surprise anyone, but I would definitely want to know more specifics before entering into any sort of clinical trial.

    I find it all very interesting too, and any treatment that safely and effectively addresses the type of inflammation thought to be responsible for persistent symptoms would be a major breakthrough.

    ReplyDelete
  2. Rita,

    I wouldn't look at research specifically for this drug - anything you find about VGV-L is either going to be on Viral Genetics' web site or a pr wire press release about it, because they are in the pre-IND filing process and just about everything about their therapy is proprietary information at this stage.

    The best thing to do is look at more general research related to the use of synthetic peptides in treating autoimmune disorders and how it might relate to Lyme disease, where chronic Lyme disease might result in an autoimmune condition.

    Check out this:
    http://www.eurekalert.org/pub_releases/2011-12/wios-nsm122211.php

    It's a link to research that uses synthetic peptides to block members of the matrix metalloproteinase (MMP) enzyme family. MMPs can cut through collagen and are heavily involved in Lyme disease - so I'd be willing to speculate that something similar to this is being used by Viral Genetics - but I'm not sure which peptides they are using and what specific part of the immune response chain they are looking to block. It may not be MMPs - it may be something else entirely, like overabundant plasma cells.

    If you find any more information, please post it here and let us all know. I'll continue to look, too.

    ReplyDelete
  3. CO,

    Yes, I suspected that the proprietary information angle would make it difficult to find anything specific, but that's never stopped me from trying. :-)

    Thanks for the tips and the link. I must say this stuff is really cool! I'll need to educate myself a bit more about synthetic peptides, and then I'll start searching for any clues. I promise to post anything that seems even remotely related.

    Rita

    ReplyDelete
  4. CO,

    I found quite a bit of information contained in various patents or patent applications where both peptides and Lyme disease are mentioned. Since patent holder addresses are included, I would prefer not to post those links publicly, however I could e-mail them to you for your review if you are interested.

    What I can share at this time is this tidbit, which I've haven't researched further because I just found it:

    http://www.prnewswire.com/news-releases/viral-genetics-researcher-and-advisor-set-to-share-award-116222294.html

    [quote]

    Viral Genetics' Researcher and Advisor Set to Share Award

    Time for Lyme Will Honor Dr. M. Karen Newell Rogers and Mr. Richard Gerstner

    SAN MARINO, Calif., Feb. 15, 2011 /PRNewswire/ -- Viral Genetics, Inc. (Pink Sheets: VRAL) announced today that lead researcher Dr. M. Karen Newell Rogers and Advisor Mr. Richard Gerstner will receive the Lauren F. Brooks Hope Award, presented by Time for Lyme, Inc. The award presentation is set for the Illusions of Lyme Gala, April 2, 2011, in Stamford, CT. Dr. Newell Rogers is being recognized for her research on Targeted Peptide treatment for Lyme Disease at the University of Colorado at Colorado Springs and Texas A&M University. Mr. Gerstner helped Dr. Newell Rogers to initiate research on a treatment for the disease and has supported her research with funding.

    "We are very proud of Dr. Newell Rogers' work and appreciative of the support that Mr. Gerstner has provided," said Viral Genetics' CEO, Haig Keledjian. "This award is a confirmation that Dr. Newell Rogers' research into a treatment for Lyme Disease is showing results."

    "I would like to personally thank Mr. Gerstner for his original gift," added Monica Ord, Viral Genetics' Senior Vice President for Corporate Development and Communications. "Since that day, and with the steadfast support of Tyme for Lyme, Dr. Newell Rogers has uncovered not only a promising treatment but new information about this disease that is invaluable. We have never had such a willingness of immediate support in any other disease as with the Lyme community. We applaud you."

    Dr. Newell Rogers and Viral Genetics are now completing the development of a molecule for the treatment of Lyme disease. This molecule is comparable to the Company's APi1177 Targeted Peptide molecule being studied for HIV/AIDS, which appears to rely on a similar underlying mechanism to assist in the control of chronic inflammation believed to be responsible for certain symptoms of Lyme Disease. Preliminary animal studies of this compound showed positive results in decreasing levels of inflammation in Borrelia infection in animals. Viral Genetics' goal is to initiate review of this drug candidate by the United States Food and Drug Administration through a pre-IND filing in 2011. Dr. Newell Rogers' research has been funded, in part, by grants from Time for Lyme, Inc., Mr. Richard Gerstner, and funding from Turn the Corner Foundation.

    M. Karen Newell Rogers, Ph.D., is currently the Raleigh R. White Jr. Endowed Professor of Surgical Research at Scott and White Hospital's Department of Surgery, affiliated with Texas A&M University Health Science Center's College of Medicine, located in Temple, Texas. She was previously at the University of Colorado at Colorado Springs, where she began her research into Lyme Disease.

    Richard T. Gerstner serves on the Advisory Board of Viral Genetics and is also on the Advisory Committee to Columbia University's Lyme and Tick Borne Diseases Research Center. He has served in executive management in numerous technology companies, including IBM and Telular Corporation.

    [snip]

    [end quote]

    Rita

    ReplyDelete
  5. I think this is infection-driven autoimmunity and inflammation, so it would seem like you would still have to treat the lyme at the same time as you treat the autoimmunity or inflammation. Otherwise, if this knocks down the immune system and there are still spirochetes around, you will get worse, just like with steroids.

    The interesting thing is that doctors have found the autoimmune markers disappear with successful lyme treatment.

    So, I would not volunteer for this treatment until I was sure they understood that infection could still be in the picture.

    ReplyDelete
  6. Anonymous,

    You bring up a good point - you don't want to just use an agent which modifies the immune system if infection is still present. The question remains though: How long should would treat with either modality, and how would one determine what the duration of treatment is?

    The one study that comes to mind related to the issue of immune system dysregulation and persistent infection is one from Finland conducted not long ago:

    Yrjanainen et al from Univ of Turku in Finland reported in J Infectious Disease (2007; 195(10):1489-96) a study which examined whether anti-tumor necrosis factor-alpha would have a beneficial effect on Bb-infected mice.

    C3H/He mice were infected with B. garinii A218 or B. burgdorferi sensu stricto N40. In study 1 (with B. garinii) and in study 2 (with Bb SSN40), 2 weeks after infection, 10 mice were treated with ceftriaxone only for 5 days and 10 mice were treated with anti-TNF-alpha only. In another group of 10 mice, anti-TNF was added simultaneous to the ceftriaxone at 2 weeks after infection while in another group of 10 mice anti-TNF was added at 6 weeks after infection (ie, 4 weeks after ceftriaxone). Finally, a fifth group of mice was treated with saline as a sham treatment.

    For the group that received ceftriaxone only, no samples were positive by culture or by PCR at 2 weeks after infection. However, among those mice treated with anti-TNF-alpha either at 2 weeks or 6 weeks after infection, spirochetes grew from one-third of the mice. Contrary to earlier findings by Bockenstedt et al (2002) in which the spirochetes detected after antibiotic treatment were attenuated in activity, the recovered spirochetes in this study did not appear to be attenuated, as ceftriaxone sensitivity rates, plasmid profiles, and virulence rates were similar to those of bacteria used to infect the mice. This study demonstrated that a portion of B. burgdorferi-infected mice still have live spirochetes in their body, which are activated by anti-TNF-alpha treatment.

    Now I don't know what entirely to make of this study. It would be good if someone else were to replicate the results and confirm it. But if this is so - and anti-TNF-alpha actually activates spirochetes, then much more needs to be known about this.

    I'm not sure whether or not Viral Genetics' synthetic peptides would operate in a similar fashion. This is one reason why I want to learn more about their chronic Lyme disease treatment. So far, I'm speculating as to how it might work based on other similar products on the market for other conditions.

    With Viral Genetics' pre-IND status, they would have already completed animal model testing so they have some idea how much of their synthetic peptide product would work for reducing inflammation and would have collected safety data for an effective dosage. But it remains to be seen if their product will work the same way in people.

    I respect your decision not to volunteer if you think that infection is still present and it is not being treated. I don't know what Viral Genetics' clinical trial design/plans will look like, though, and whether or not antibiotic use would be part of any of the treatment arms. We'll just have to wait and see.

    I am not sure whether I would do it or not. I know there are risks involved in any trial. I probably couldn't make my own decision until I saw who was conducting the trials and how they were designed.

    ReplyDelete

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