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PR: FDA to Rule on Testing New Drug for Chronic Lyme

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PR: FDA to Rule on Testing New Drug for Chronic Lyme

Postby rlstanley » Mon 2 Apr 2012 17:28

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http://www.prweb.com/releases/prweb2012 ... 353599.htm

FDA to Rule on Testing New Drug for Chronic Lyme

Stamford, CT (PRWEB) April 02, 2012

Researchers led by Time for Lyme grantee, M. Karen Newell-Rogers, Ph.D, have submitted a pre-IND briefing document to the US Food and Drug Administration, a preliminary step toward developing proposals for clinical testing of a new drug that could one day end the suffering of those with chronic, or long-term Lyme disease.

“To our knowledge this is the first novel drug candidate that has been proposed for study in the treatment of chronic Lyme Disease post-infection in some time,” said a representative of Viral Genetics, that submitted the proposal for its drug candidate, VGV-L, to the FDA. A response is expected in April.

Tests led by Dr. Newell-Rogers, a professor at Texas A&M Health Science Center College of Medicine and Scott & White Hospital, and a scientific advisor to Viral Genetics, have been conducted for over two and a half years. The results were submitted this month to the FDA, along with a protocol for a proposed human clinical trial designed under the guidance of a leading Lyme clinician at one of the nation’s top medical centers. Testing to date was conducted by Dr. Newell-Rogers with significant contributions from other clinicians at the University of Colorado, Texas A&M Health Science Center and Scott & White Hospital in Texas.

Prior research had established the insight that certain immune characteristics may contribute to whether a person is susceptible or resistant to the development of chronic inflammation as a result of infection. Dr. Newell-Rogers theory proposes a “targeted” peptide to replace or remove the self-peptides and restore a healthy immune response in patients.

Much of the funding for the pre-clinical studies leading to the FDA filing was provided by Time for Lyme, acting in concert with Richard Gerstner, the ex-IBM Executive VP who saw the potential applicability of Dr. Newell’s work, to Lyme disease.

Time for Lyme has raised over $5 million since its founding in 1998 to fund research on Lyme and other tick-borne diseases at esteemed institutions across the U.S., including the establishment and endowment of Columbia University Medical Center’s Lyme and Tick-borne Disease Research Center.

“Time for Lyme is focused on its clear and single mission of promoting research into Lyme and tick borne diseases,” said Peter Wild, executive director of the organization. “At present there is no recognized treatment for Lyme once it has developed into its chronic, long-term state. We are hopeful that Dr. Newell-Roger’s work will provide the solution that long-term Lyme disease sufferers have been hoping for, for decades.”

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Re: PR: FDA to Rule on Testing New Drug for Chronic Lyme

Postby rlstanley » Mon 2 Apr 2012 17:41

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http://www.viralgenetics.com/investors/pr_030712.php

Press Release
Source: Viral Genetics, Inc.

Viral Genetics Submits Pre-IND Document for Lyme Disease Drug Candidate to FDA.

First Potential Treatment of its Kind for Chronic Lyme Disease Sufferers is Second Candidate Developed from Company’s Targeted Peptides Platform.

Company Also Notes That Research 2.0 Completes Updated Report on VRAL's Growth Prospects.

Business Wire
San Marino, CA (PRWEB) March 7, 2012



snippet

Viral Genetics (Pinksheets: VRAL.PK - News) announced today that it has submitted a pre-IND briefing document to the US Food and Drug Administration (FDA) for its Lyme Disease drug candidate, VGV-L, marking important milestones for both the Company and its supporters in the Lyme community.

“To our knowledge, this is the first novel drug candidate that has been proposed for study in the treatment of chronic Lyme Disease post-infection in quite some time. We are equally pleased that it represents the second drug candidate we have developed from our licensed Targeted Peptides platform,” said Haig Keledjian, President of Viral Genetics. “Our shareholders should be proud that our team managed to bring a drug candidate to this step of preliminary FDA review within about 30 months. Within the single Targeted Peptides platform, we are also developing candidates for treatment of sepsis, staphylococcus and streptococcus infection, multiple sclerosis and other conditions, while we continue to complete IND-enabling preclinical testing for our HIV/AIDS candidate.”

The pre-IND submission provides extensive research information gathered by Viral Genetics’ researchers over a 2 ½ year period of rigorous and detailed testing which resulted in positive results, to the FDA, along with a protocol for a proposed US human clinical trial designed under the guidance of a leading Lyme clinician at one of the nation’s top medical centers. Testing to date was conducted at the University of Colorado, Texas A&M University, Scott & White Hospital, and has been led by Viral Genetics Chief Scientist, Dr. M. Karen Newell-Rogers, with significant contributions from several clinicians.

The Company anticipates that the response to the pre-IND submission will be received in March-April 2012. While the FDA’s written responses to pre-IND submissions are typically comprehensive, in some cases the need for additional clarification or discussion necessitates a meeting in person or by teleconference.

The written pre-IND response typically provides detailed insight into the FDA's concerns about available information on a particular drug being proposed for human testing in a particular patient population, and helps preempt any potential deficiencies that the FDA may find upon submission of the full IND application. This feedback acts as a kind of blueprint that guides the sponsor’s completion of the full IND towards attainment of FDA clearance to proceed with the proposed clinical trial. Post-submission of an IND, FDA reviewers may need clarifications or additional information before making a decision. FDA requirements for an IND include detailed information on all aspects of the proposed product such as manufacturing, preclinical and clinical testing, scientific background, proposed clinical development plan, clinical protocol, etc. This information needs to be presented in a format aimed towards clarifying the rationale of the proposed clinical trial, and for ease of review by the FDA reviewers.

Funding for some of the pre-clinical trial studies leading to the filing was initiated by Viral Genetics advisor, Richard Gerstner, former head of IBM’s Asia operations and later the company’s personal computer division. In April of 2011, Mr. Gerstner, who faced a long battle with Lyme during his tenure at IBM and his subsequent career in the venture capital arena, was a recipient, along with Dr. M. Karen Newell – Rogers, of the Lauren F. Brooks Hope Award, given by the Time for Lyme Foundation. Since the commencement of Time for Lyme’s fundraising efforts in 2001, it has raised nearly $5 million and partnered with Columbia University Medical Center to create its Lyme and Tick-Borne Disease Research Center. Past recipients of the award include Nobel Laureate Dr. Luc Montagnier, also an advisory board member of Viral Genetics, and world-renowned pediatrician Dr. Charles Ray Jones.

This research was further supported by grants from the Time for Lyme and the Turn the Corner Foundation who both saw the promise in Dr. Newell-Roger’s approach, helping it to reach this phase of development and the pre-IND filing. The proposed therapy, like several others in Viral Genetics R&D pipeline, is based on Targeted Peptide technology (TPT) and uses synthetic peptides to "trick" cells that may be responsible for harmful symptoms, making them vulnerable to the body's natural immune response mechanism.

Emphasizing the platform nature of the TPT approach, Dr. Newell-Rogers expanded on how TPT potentially may be targeted to a number of potential diseases or “indications” that have proved stubbornly resistant to more traditional approaches such as, in this case, chronic Lyme Disease. “The idea behind our research is that those with a genetic blueprint that does not allow certain self-peptides to be processed or removed tend to mount a chronic inflammatory immune response that is not properly controlled. In terms of drug development, we believe that many diseases and chronic illnesses may be dependent in important ways on this harmful type of inflammation,” Dr. Newell stated. Her theory proposes a “targeted” peptide to replace or remove certain self-peptides and hopefully restore a less harmful and more specific immune response in patients. The studies conducted by Viral Genetics aim to shed light on this chronic inflammatory response and symptoms shared by a significant subset of Lyme disease patients.

Currently there is no treatment for Lyme Disease once it has developed into its chronic, long-term state, other than antibiotics regimens which, while managing the disease for some of those infected, leaves untouched some of the symptoms for a significant portion of those suffering from this debilitating condition.

“Dr. Karen Newell and her team have done a tremendous job unraveling many of the complexities of Lyme disease. We are extremely grateful for the support, heartfelt pleas, and input of so many physicians from the Lyme community. Our focus now is to move this as quickly as possible through the clinical stage with top tier Lyme Literate physicians and research institutions. Our goal has been and will continue to be walking this successfully through approval for the suffering Lyme community that desperately needs it. We could not be happier,” said Monica Ord, SVP of corporate development and communications.

The pre-IND submission filing for VGV-L is one of three drug candidates in Viral Genetics’ pipeline that are nearing FDA review and clinical trial status. This includes an oncology trial at Scott and White hospital of the Company’s Metabolic Disruption therapy which went from being a relatively small, single-site, more traditional 'physician's study' to potentially a dual-site, larger study consisting of upwards of several dozen patients with a second (or 'co-') primary investigator that may be a Phase 1 or Phase 2 study.

In a final comment, Mr. Keledjian noted that equity research firm Research 2.0, has completed its latest update on VRAL. The report highlights the exciting “pivotal year ahead”, and details the company's progress on both the biological sciences front and the algal biofuels opportunity for the company's VG Energy subsidiary. The report provides insight into the various market opportunities and posits a framework for the company's growing valuations.

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Re: PR: FDA to Rule on Testing New Drug for Chronic Lyme

Postby Claudia » Mon 2 Apr 2012 17:48

Rita, with your educational background, what are your thoughts about this?
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Re: PR: FDA to Rule on Testing New Drug for Chronic Lyme

Postby rlstanley » Tue 3 Apr 2012 2:41

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Claudia:Rita, with your educational background, what are your thoughts about this?


Don't have access to anything on it; don't know what TPT entails; would have to dig and see what is out there. I'll look and see what I can find. These are just Press Releases by PR Web.

Red flags, of course, leave me skeptical; here's one:
Our focus now is to move this as quickly as possible through the clinical stage with top tier Lyme Literate physicians and research institutions


Uh huh.

Perhaps others have info. I'll look around to see what I can find. I remain skeptical; that's what my background taught me. Press releases don't convince me of anything.
.
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Re: PR: FDA to Rule on Testing New Drug for Chronic Lyme

Postby Claudia » Tue 3 Apr 2012 17:03

Thanks so much, Rita.

I just saw that Camp Other has a blog post on this, and has pulled together some related information. I need to read through it carefully to begin to understand it: http://campother.blogspot.com/2012/04/v ... e-for.html
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Re: PR: FDA to Rule on Testing New Drug for Chronic Lyme

Postby Camp Other » Tue 3 Apr 2012 20:48

I did as much poking around about Viral Genetics' new chronic Lyme disease candidate drug, VGV-L, as I could and it wasn't easy. One CV, several patents, and a few Dr. Karen Newell Roger interviews later, and the best I could get out of it is that it is not just a synthetic thymus peptide that they patented but a method of replacing a peptide, CLIP, on the surface of B cells with this synthetic thymus peptide (which somehow maps to the MHC genetic type (HLA) of the patient) so that it activates Treg cells. The activation of these Treg cells is supposed to lead to reduction of non-specific B cells (polyclonal B cell activation).

In the patent, there is also mention of using bacterial antigens and antibiotics as adjunct treatments which are optional. The impression I'm left with is the bacterial antigens are used to prime new B cells and if there is any existing infection, antibiotics are used.

So the entire method of treating patients may be: a) VGV-L alone, b) VGV-L and antigen exposure, or c) VGV-L, antigen exposure, and antibiotics are used. (antivirals and antiparasitics may also be used, depending on the patient's diagnosis)

All of this has been pretty difficult to write about; I think my most recent post about it requires an update if not a rewrite.

I don't get the impression after reading everything I've read thus far that chronic Lyme disease is a pure B-cell disorder. But maybe it's a variant on that? Maybe cell-mediated immunity is somehow affected by B. burgdorferi?

I think we need to consult with an immunology researcher about this. It does get pretty complex, and there is already controversy around the role of polyclonal B cell activation in infection.

Also, if anyone went to the Canadian Lyme disease conference that was held a few weeks ago and saw Dr. Karen Newell Rogers speak there - perhaps they would have more information about VGV-L?
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Re: PR: FDA to Rule on Testing New Drug for Chronic Lyme

Postby Camp Other » Wed 4 Apr 2012 9:26

I've made a major edit on my blog entry. I still think I need a revised version of the post to be made in the future, but I am so exhausted at the moment that I think it won't be for a few days at least. Maybe call it the revised executive summary version, because the current post is rambling even relative to rambling for me.

Why do I mention this edit here? Because it is very important to note, relative to how I infer the way VGV-L has been hypothesized to work:

The edit was about Tunev and Barthold's research on lymphadenopathy in Borrelia burgdorferi infection in mice. In their research, they noticed an outsized B-cell response to the presence of spirochetes. However, what they found differed from what has been found in polyclonal B-cell activation in other infections - where it's clear runaway non-specific polyclonal B-cell activation leads to autoimmune disorders. In Tunev and Barthold's research, the outsized immune response had B-cells which were specific for Borrelia burgdorferi yet were of low quality. This is notably different from typical polyclonal B-cell activation.

I don't know how this difference in response would work with VGV-L. It isn't clear to me, and I have to read through more research to understand it - at least hypothetically. I also want to know if anyone else has used similar technology to treat pure B-cell disorders and if so, what the pros and cons were. If this is a completely novel invention, then it's harder to evaluate and all one can do is look at the animal trials if one has access to them and examine the underlying hypothesis for its application.

The paper that this technology primarily appears to be based on is this one:

M. K. Newell, R. P. Tobin, J. H. Cabrera, M. B. Sorensen, A. Huckstep, E. M. VillalobosMenuey, M. Burnett, E. McCrea, C. P. Harvey, A. Buddiga, A. Bar-Or, M. S. Freedman, J. Nalbantoglu, N. Arbour, S. S. Zamvil, and J. P. Antel. 2010. TLR-Mediated B Cell Activation Results in Ectopic CLIP Expression that Promotes B Cell-Dependent Inflammation. Journal of Leukocyte Biology.
Online e-Pub. July 14, 2010.

Link to free full text of this publication: http://www.ncbi.nlm.nih.gov/pubmed/20631258

I'll just post the abstract here, and you can read the entire text at the link above:

Abstract

Infectious pathogens produce compounds called Toll ligands that activate TLRs on lymphocytes. Acute activation triggered by certain TLRs appears to "jump start" the innate immune response, characterized by the release of inflammatory cytokines and cellular expansion.

In some individuals, there is a failure to control acute inflammation, resulting in postinfectious, chronic inflammation. Susceptibility to chronic inflammation is strongly associated with an individual's MHC genes. Recent clinical trials for several autoimmune diseases characterized by chronic inflammation suggest that B lymphocyte depletion therapies dampen chronic immune activation. However, currently, there is no known mechanism that accounts for the correlation among TLR activation, MHC genetics, and a pathological role for B-lymphocytes.

Our hypothesis is that TLR-activated B cells (B cells that have been polyclonally activated in the absence of antigen-specific signals) are not controlled properly by T cell-dependent B cell death, thereby causing B cell-dependent chronic inflammation.

Here, we show that treatment with Toll ligands results in polyclonal B cell activation accompanied by ectopic expression of CLIP. Furthermore, by adoptively transferring purified CLIP+ B cells in syngeneic animals, we find that CLIP+ B cells induce production of TNF-α by host T cells. Finally, we demonstrate that CLIP-targeted peptide competition results in the death of polyclonally activated CLIP+ B cells.

--------

I think part of the reason I had trouble writing about VGV-L is terminology... it isn't always clear when they are talking about B cells which have already been targeted using peptides in the documentation I've read.

I need sleep, coffee, and a re-read. Then days later, revision or a new post.

Anyone reading this have ideas on how VGV-L might affect B cells which are low quality but are antigen specific for Bb and have been generated into isotypes? I'm curious to hear your perspective on this.
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Re: PR: FDA to Rule on Testing New Drug for Chronic Lyme

Postby Claudia » Wed 4 Apr 2012 14:46

Camp Other, this is really complicated to understand for the average layperson such as myself. You do a great job on your blog of putting up accurate medical science information, dissecting what it means or could mean, and making it as easy as possible to comprehend without dumbing it down. I am sorry if my premature linking to your blog post here caused unexpected work for you before you were ready to really get into it over there. But thank you for that, and for your replies here. It is really appreciated, and very helpful.

I hope that others that are knowledgeable will chime in, too, and help you with your questions as well.
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Re: PR: FDA to Rule on Testing New Drug for Chronic Lyme

Postby Camp Other » Wed 4 Apr 2012 18:08

Claudia wrote:Camp Other, this is really complicated to understand for the average layperson such as myself. You do a great job on your blog of putting up accurate medical science information, dissecting what it means or could mean, and making it as easy as possible to comprehend without dumbing it down. I am sorry if my premature linking to your blog post here caused unexpected work for you before you were ready to really get into it over there. But thank you for that, and for your replies here. It is really appreciated, and very helpful.

I hope that others that are knowledgeable will chime in, too, and help you with your questions as well.


Claudia, thanks for the compliment. I'm doing my best, but I have to issue a caveat: I am not an immunologist, so what I write about this subject is limited to my understanding of immunology at this time (translation: education which is somewhat dated at this point). I am good at finding as much information as I can which relates to the hypothesis behind VGV-L's development and demonstrating relationships between what has been discussed in the field as a whole and what has been researched which relates to B. burgdorferi, but there my ability to describe what is happening ends. An immunology researcher with sufficient experience dealing with Borrelia and spirochetal infections would be a better person with whom to discuss this - I wish we could get one on board here.
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Re: PR: FDA to Rule on Testing New Drug for Chronic Lyme

Postby Camp Other » Wed 4 Apr 2012 19:11

I've had sleep and some coffee. I don't know if I'm ready for that revision or executive summary post yet.

I think I know at this point what my missing pieces are now:

- describe the role of Treg cells (regulatory T cells) and how they relate to killing off B cells and generating more targeted immune responses.

- describe the hypothesis that Foxp3+ Treg generation in the thymus is somehow dysfunctional in those with persisting symptoms (I think this has some relationship to the core hypothesis behind VGV-L's use).

- And I have to more clearly state that even if the Foxp3+ Treg generation is what it is happening, there may be some risk involved in proceeding with this kind of treatment. Wikipedia managed to explain some of it, and while Wikipedia is not the most reliable resource on everything, it is relatively easy to follow and this particular entry (so far) jives with what I've seen in other sources:

http://en.wikipedia.org/wiki/Foxp3

This is also not half bad, and recommend checking it out:
http://en.wikipedia.org/wiki/Polyclonal_B_cell_response

Plus, of course, there are the papers I link to on the blog.

The more I delve into this, the more questions I have... Tunev and Barthold's paper, in particular, lead me to wonder if the hypothesis underlying VGV-L's design developed with the scenario described in their research being taken into account. Between T & B's research plus other publications, I get the impression that in at least the animal model of immune response to Bb, that there is a mixed state response to it - It is both immune suppressing and immune stimulating. Some research has even indicated a certain amount of tolerizing is involved. (http://en.wikipedia.org/wiki/Peripheral_tolerance - anergy plus inflammation; see also http://users.ox.ac.uk/~path0116/tig/tolg2.html for a more detailed explanation)

Adding a bacterial antigen/adjuvant (and possibly antimicrobial medicine) to the treatment may be a way of working around this combination, in order to produce new B cells which are stimulated and respond specifically to Bb and not be nonspecific - and in order to eliminate any remaining infection if there is one present.

This is complicated - and while more and more is being learned about immunology every day, there are still an enormous number of unknowns. I would want someone else with more background to explain the pros and cons here. Perhaps asking Dr. Newell Rogers some questions about this is next if we can't find anyone on board to ask.
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