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Re: Anyone know the latest on the Ceres Nanotrap

Posted: Mon 31 Oct 2016 16:42
by Henry
The Ceres nanotrap method used to detect OspA in urine reminds me very much of the old --and now abandoned-- Lyme Urinary Antigen Test (LUAT) that was advocated by many LLMDs and likewise was used to detect OspA, as well as other Borrelia antigens, in urine. It has been discredited as a reliable diagnostic test (see : http://www.cdc.gov/lyme/diagnosistestin ... index.html ).

There is not a very good history of urine-based diagnostic tests for Lyme disease. Consequently, the people at Ceres are going to have to come up with solid proof for validation of their method certainly to get FDA approval. In the mean time, I would not but any stock in that company...............

Re: Anyone know the latest on the Ceres Nanotrap

Posted: Mon 31 Oct 2016 22:21
by velvetmagnetta
OK, hv808ct. Pile it Higher and Deeper. I do still believe, however, that you could be a scientist working in the Lyme field. Unlinke Henry, you have not claimed anything scientifically questionable to make me believe otherwise.

(Except, perhaps, that the horrible pain people are in after a Lyme infection should have been eradicated with antibiotics is just the normal aches and pains of everyday life! But many scientists in the Lyme field have claimed as much, it doesn't necessarily mean you are not one of them.)

But really, aybody could be anybody online, so I encourage everyone reading posts online do their own research, ask known professionals in person, and then draw your own conclusions.

This Lyme test is not the same as that other one Henry mentioned - yes, I know they both have the words "antigen" and "urine" in their titles, but the Ceres test uses a very new carbon nanotube technology.

So, I think by now everyone knows about the reciprocal relationship of Osp A and Osp C. I guess, so the question becomes: Is this test sensitive enough to pick up on some very low quantities of Osp A? Remember, this test does not look for our bodies' response to the Lyme infection, but the actual OspA on the actual spirochetes themselves.

Re: Anyone know the latest on the Ceres Nanotrap

Posted: Mon 31 Oct 2016 22:37
by velvetmagnetta
Kiki- I tried sending you a Private Message (PM), but for some reason it found you but wouldn' let me select your name for the "To" box in the message. Do you have an account here? I though you needed one to post, but it's been so long since I've joined that I can't remember. Do you have a log-in username and password?

Re: Anyone know the latest on the Ceres Nanotrap

Posted: Mon 31 Oct 2016 22:59
by Henry
Recently, the FDA revised its policy concerning laboratory developed tests (LDTs). It is going to be tougher for Ceres to get its test approved. See: http://www.nytimes.com/2014/08/01/busin ... .html?_r=0 . So, now let's see how good the test is. It will have to pass this test before it can be marketed as a diagnostic test.

Re: Anyone know the latest on the Ceres Nanotrap

Posted: Wed 2 Nov 2016 0:48
by velvetmagnetta
OK. So I really don't know enough to properly defend this test. But what I do know is that this company and this nanotube technology are very good and very exciting for the future of Lyme diagnostics and treatment. And in this way, yes, you actually should buy stock in this company - I have no idea if this is a publicly-held company, but if it is, I would definitely buy stock in it (if I had any money to do so, that is!)

OK, so I thought I'd find out straight from the horse's mouth what the deal is with this Osp A down-regulation business and what it means for the test. And not 2 days later, they wrote me back in much detail!

The question I asked was this:
Hello! I am very excited about your new nano tech inspired test. I think the is wonderful technology and should be widespread soon. But, I regularly read a Lyme disease message board called Lymnet Europe (NOT related to Lymenet in any way) and someone there has pointed out the OspA is downregulated as OspC is upregulated in animals shortly after infection. OspA is found in abundance inside the tick's midgut, but not so much when the spirochete is inside the human or animal host. I know this test is capable of detecting very low quantities of OspA antigen, but is it sensitive enough? Does OspA being downregulated mean that it is not present at all? I have been trying to defend this test on that website, but find I do not know enough to properly defend it. Please tell me if and how this test will still detect antigens that are down-regulated?
And their answer to this was:
Here is our pathologist’s response to your question:

Dear (My Name Here),

Thank you for this very good question. Our initial goal of the nano trap test was to detect Lyme disease very early, soon after the tick bite, and in the first 30 days prior to the patient developing a robust immune response. For this intended use we chose OspA because it is the earliest protein antigen in early stage disease and has been definitively detected by mass spectrometry in the blood of Lyme patients. The conclusions you cite that OspA is only expressed by the spirochete in the tick, and is down regulated afterward, is based on measuring antibodies to OspA in the patient, not by measuring the OspA antigen itself. Antibodies to OspA are found in patients with Lyme Arthritis if Lyme persists untreated. Osp A is expressed in abundance in actively growing spirochetes in vitro in culture without the tick. 

 

We chose a new epitope of OspA that is conserved across all species of Lyme. When we tested our assay in true positive early stage EM rash positive patients, prior to treatment, we found a very high sensitivity and specificity. Nevertheless we also found OspA in later stage disease in some patients with persistent symptoms. We found that our test switched from positive to negative after antibiotic treatment. 

 

Our test uses an epitope mapped specific antibody and a second stage competition. Thus we achieve very high specificity. From our point of view OspA should not be present in a patient's urine unless they have an active Lyme infection.

 

It is an open question which of all the many pathogen Lyme protein antigens (different from the serology antibodies) are present, and at what levels, at different stages of the disease. Since Lyme resides mainly in the tissue compartment, concentration of an antigen in the blood may be unrelated to the levels of the patient's antibodies against that same antigen. To definitively answer this question, we are developing a highly sensitive and absolutely specific test for a panel of ALL the major Lyme antigens. We will then apply this panel to patients at all stages of the disease before and after therapy.

 

I hope this answers your excellent question.

 

Sincerely,

(Pathologist's name here)*

*I did not ask permission to post the pathologist's name publicly.
I hope this adequately answers any questions or doubts people reading this thread may have. If not, feel free to write to them yourselves, their contact info is right there on the Ceres Nano website. (And please post your questions and answers in this thread just in case someone else might have the same question?) This is a real company with very real and state-of-the art technology - And sorry to disappoint some of you, but they won't be going out of business any time soon.

But their answer also gives migs and others in that situation hope that when Ceres completes their lengthy new panel of antigen proteins to detect that you WILL have a difinitive answer to whether you are presently infected with any of the various Lyme spirochetes.

Unfortunately, this wonderful test will tell you nothing about whether you are infected with some other Lyme-like pathogen or virus, nor will it tell you if you are now suffering damage to your nerves and tissues, etc. from a past Lyme infection.

But hey, it's a start. And as you can see from their response, there in fact ARE people with Lyme who have taken antibiotics for it and yet they are still infected with Lyme. I believe this situation is called "Chronic Lyme Disease" but I don't want to speculate - especially not in front of our trained monke...I mean our trained microbiologists - if there really are any out there reading this. ;)

Re: Anyone know the latest on the Ceres Nanotrap

Posted: Wed 2 Nov 2016 1:14
by Kiki
Henry--

Haha….. You think *I* should do more studying!?!

I have been brief with my responses and explanations so far because this isn’t worth my time, but now I must. You are infecting hope with splintered, fragmented truth and the illusion of knowledge. Sufferers do not deserve this.

This link (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC42328/) that you recently provided is laughable. It is only explaining the expression of OspA & OspC during the FEEDING OF A TICK! The transfer of Borrelia burgdorferi! That's where you choose to rest your argument? Host response is the key role in disease pathogenesis.

The downregulation of OspA is required to successfully infect mammalian hosts. As soon as the sucker hits warm blood (please refer to the link you provided) it is rapidly down-regulated. This is an excellent transmission strategy because OspC is not always an immune target and OspA is.

If this conversion doesn’t happen quickly enough the EM rash will develop, which explains why some people get the rash and some don’t. This of course triggers a strong immune response, which the bacteria responds quickly to by altering protein expression. Sometimes expression of the disease is delayed, but as soon as the immune system (or antibiotics) threatens the bacteria it takes evasive maneuvers. This back and forth cycle repeats itself over and over again.

Borrelia is (nearly) genetically and morphologically perfect. It understands human immunity and adjusts itself accordingly.

You don’t like Ceres’ choice of OspA. Yes, the expression of OspA is variable, but it is highly conserved and always found in ACTIVE lyme (when a patient is symptomatic), making it the perfect choice. This allows for the distinguishment between symptomatic and infected patients, and symptomatic non-infected patients. You should be ecstatic about this--seeing how heavily you criticize those who report persistent and recurrent LB.

I agree with you on one thing, Henry. C-6 is constant and abundant and would be a great choice, except for the fact that it persists even after successful antibiotic treatment. The Nanotest will be able to determine if the first round of antibiotic treatment was successful or if a second is needed--meaning, you can monitor treatment success! There is currently no way to know if a patient is cured of LB because the immunological memory of the disease is retained.

The Nanotest sensitivity and accuracy is massively enhanced to the CDC standard test. It attracts like a magnet a single and very specific epitope of OspA that is both easily distinguished from human serum proteins and unambiguous of the bacteria. The Lyme Urinary Antigen Test was incapable of this and 1000x less sensitive.

The Ceres laboratory has all the certifications they need to perform the test and diagnose patients, and as I said before, the Nanotrap test is in final stage of FDA approval. All they have left to do is create a diagnostic kit.

Nanomedicine is poised to take the clinical and diagnostic world by storm. A microbiologist should be deliriously enthusiastic about this!

Enough said.

Re: Anyone know the latest on the Ceres Nanotrap

Posted: Wed 2 Nov 2016 1:24
by Kiki
Velvetmagnetta, we must have posted at the same time. Consequently I repeated much of what you just said. Sorry!

I love that you emailed Ceres about this! They are always so helpful. BTW, I PM'd you. Did you get it?

Re: Anyone know the latest on the Ceres Nanotrap

Posted: Wed 2 Nov 2016 1:36
by duncan
Kiki, I agree with most of what you and VM have been saying. I'd like to add, when trying to figure out why some might reject any new test, it may be prudent to learn whether they have interests in the status quo of the present $500,000,000 Lyme diagnostic market.

But quick question: What makes you think the C6 remains positive after SUCCESSFUL abx treatment? It certainly can remain elevated after treatment, but couldn't this be indicative of unsuccessful treatment? I think the official line is that most "old guard experts" cannot explain away persistent elevated C6 values post-treatment (unlike conventional ELISA or even WB results, where immune memory is invoked) - but the simple reason for that is that C6 values remain high because the infection remains.

Re: Anyone know the latest on the Ceres Nanotrap

Posted: Wed 2 Nov 2016 3:10
by velvetmagnetta
Hi Duncan - that's a good question. I have no idea what the answer is, but I hope when Ceres completes its more thorough Lyme panel and the technology becomes more affordable and accesible (which will be soon!), you won't have to worry about it any more.

Kiki - I am ecstatic about what you wrote! As I was reading it I thought, "Hey this sounds really familiar," and I thought you might really be the pathologist from Ceres!!

See? Anybody could be anybody on the internet! But by the end I realized that you are a long-suffering, well-informed patient just like so many of us here on Lymenet Europe.

I was pleasantly surprised at how quickly Ceres answered my question. I see you have been in communication with them, too. I'm starting to really like this company. I saw on their website that they are doing work with this diagnostic technology in all sorts of disease fields - including cancer. Very impressive.

I wonder if they've ever considered drug delivery with carbon nanotubes?

Re: Anyone know the latest on the Ceres Nanotrap

Posted: Wed 2 Nov 2016 15:02
by Henry
Velvetmagnetta: You really must re-read my previous postings, if you read them at all. There, I said that OspA is expressed on Borrelia when cultivated on artificial laboratory media and in the midgut of ticks; however, there is reciprocal expression of OspC vs OspA during mammalian infection in which case the expression of OspA is down-regulated . Both you and the pathologist at Ceres must have missed (or more likely ignored) the fact that I also cited data derived from human studies ; those studies also substantiated the point re: reciprocal expression (see: http://jid.oxfordjournals.org/content/1 ... 8.full.pdf ). So, I have presented human host response data on this issue, as well as what happens in ticks.

I never questioned the specificity of OspA for for all strains of Borrelia, or the fact that it is expressed by Borrelia cultured on artificial media. I am quite willing to concede that the Ceres nanotrap method is able to detect small amounts of OspA if it is present in sufficient amounts during mammalian infection. It is just that, in view of what is known and evidence that I have cited about the expression of OspA during mammalian infection, the odds are very much against success.

With respect to whether OspA is a better "immune target" than OspC (whatever you meant by that expression), most of those who have been involved in the development of vaccines for Lyme disease understand that OspC indeed is a virulence antigen and would therefore be an ideal candidate for a vaccine. However, the biggest disadvantage is the extent of genetic diversity associated with OspC (at least 23 different genotypes, some of which are more important than others in the severity of infection) that is much greater for U.S. vs European strains of Borrelia. That's the only reason it has not been given more consideration for use as a vaccine. One would have to construct a vaccine that would be a combination of several (which ones?) different genotypes to ensure significant protective immunity in an endemic region.

Some of your views about the EM rash are without foundation. There is no evidence that the expression of an EM rash is dependent upon the expression/presence of OspA. Would you please cite evidence to support that claim? Or is that just another one of your wild fantasies that you got from reading "Cure Unknown", which is not a reliable source of factual information about Lyme disease?