Overview of the current commercial situation on prion diagnostics

Updated: 7 March 2005

• Review of companies involved in TSE diagnostics
• Post mortem testing of brain tissue
• Post mortem tests on their way
• Ante-mortem non-specific tests
• Ante-mortem specific tests (for PrPsc in blood)
• Editorial concerning their potential success
• If the companies would just talk to each other....
• US test market for cattle
• Ante mortem test: the big prize
• Stock Market funding
• Beware!!!
• Index of companies involved in prion diagnostics
• News on diagnostics companies (dont forget latest full TSE news)

Overview By Consultant Editor, Dr Steve Dealler:

However, as a short review:

• Post mortem tests of brain tissue: These are, at the moment, the only ones that could be looked on as being valid even in symptomatic animals when testing cattle under the European Commission.  (They cannot be looked on as being capable of demonstrating that an animal is not infected or to test blood for infectivity).
• Idexx test is currently used in the USA for testing of deer for CWD and BSE.  It has now got its license (now a much more strenuous testing to gain this license than many of the previous systems). Like the CDI-5 test it is quick, relatively simple and does not require well trained staff.  However, Idexx's test can be used in any laboratory that uses standard equipment and can  be easily, and cheaply mechanised.  Also the ELISA method that is used is well known to many people in laboratories and its microtitre trays can  be stored and transported easily for relatively long periods.
• Sanyo Junyanku have taken the rights on the test that Idexx have got, but they are only available in Japan.
• BioRad test ELISA systems (now licensed from CEA) shown initially to be 100% sensitive and specific.  Biorad's test was originally taking most of this market but it is clear that the current winners are not improving their methods adequately to permit them from being wiped from the field at a later date. At the moment there is a tendency by BioRad to claim that Idexx's test is producing false positives.  Well, we are also seeing false results from BioRad and probably the results seen were because BioRad's test may have got the test falsely negative!  (I am willing to discuss this statement).
• Prionics blotting system, shown to be 100% sensitive and specific but is relatively complex and expensive.
• Abbott's ELISA system (bought from Enfer in the Republic of Ireland),  shown initially to be 100% sensitive and specific.  Licensed in USA and Europe. Relatively expensive, and complex but was taken through the European Commission testing early and so got an easy ride.
• Aventis Behring/Beckman-Coulter have taken on the CDI-5 test from InPro seems good.  The use by InPro of europium labelling of the antibody and then time-resolved fluorimetry testing may make their method more sensitive than others.   Their hope was to take out background noise by separating PrPc and PrPsc interaction with antibodies due to the folding shape.  They then require complex equipment that is not present in many laboratories. Already they have had to go back and use the proteinase K to avoid problems and that is bound to turn out with false negatives, further problems,  and a more complex method. Prusiner and Safar have good patents and InPro to some degree are doing well from the Nobel Prize that their department at UCSF have gained...But whether it will win the economic fight is not clear.
• D-Gen test.  Dr Collinge's Imperial College group (through D-Gen) have an antibody that is specific for the prion form but I think they are all likely to have the same difficulty with background noise as previous groups (even after Western blotting systems are used).  Their selling of systems through IGEN seems much more of value but again this is seems unlikely to be a winner.
• Lelystadt group test. The excellent scientific research from Lelystad in Holland must, in my view, put them in a leading position to confirm a case of BSE but would not be good for screening. No commercial value has come form this.
• Post mortem tests on the way: They have shown PrPsc antigens present very early in the incubation period of the scrapie in their breed of sheep that always develop the disease. I suspect the system from
• Rubenstein's group on Staten Island may be too complex to carry out without the backing of major biodiagnostics corporations.  The fact that Roche seem to be interested, and another group in the USA Mid West have come out with a very similar method they have tested on scrapie sheep, may give this a chance.....but what we will find is that the test is non-specific and no patent will stand.
• PDL's strip tests sounds great but it will have to be assessed by the EC and shown to be as sensitive as other methods or it will not be looked on as acceptable for political reasons.  One of the major problems with the selling of these tests is simply in getting hold of enough samples with which to try it out!  The EC demand that they must validate the methods completely before they are permitted and hence it is likely that methods are available in USA before the huge market in Europe is open them.
• Ante mortem non-specific tests: These tests look for other changes in the blood or physiology that are due to damage to the body due to the prion disease.  As a result what is happening is that they will become positive relatively late in the incubation period.  Don't forget that currently tests are being done by looking for EEG changes, CSF changes in 14-3-3 protein and by CAT scanning looking for changes in the opacity of the caudate putamen region of the thalamus. All these are relatively late.  It is unlikely that any non-specific test will be useful in testing blood for blood transfusion.
• Roslin Institute.  Their test for EDRF has indeed shown that there is a specific range of normality in very large numbers of patients' bloods used for blood transfusion.  Now all they need to do is to show that prion infected humans have a different range.  This is potentially quite hard work.  The dreadful changes that have taken place in the UK limiting research ethically has made Roslin's work much harder.
• Proteome Sciences have found a protein in the blood of patients with CJD that is found at a lower level in normal patients. Although this is bound to require further tests on any positive result, it can be looked on as quite a find.
• Boehringer-Ingleheimhave taken over Mark Roger's and Matthias Giese's test that involves looking for PrPc, laminin receptor and gamma interferon... again as non-specific tests which would require a further test for full diagnosis. In my opinion, much more work is likely to be required on both the BI and the Proteome tests before full commercialisation.
• IGER's method may, I think, turn out to be too non-specific until later in the disease also but I would not have thought it would be a potential screening system as it seems to require electrophoretics to avoid the background noise.  At that point it may be extremely useful to confirm a positive result on a screening system (e.g. if a positive test appears on Microsens' system for instance).
• TSEnse method is extremely interesting in that one of the first pieces of damage in the animal's body is to be found in the vagus nerve and that is exactly what the method tests.  However many other things must do some damage to breathing or heart rate connection and hence any animal that turns out to be positive by his method may need to be shown to be positive by another method later before it is accepted as being infected.   The method should certainly be watched as there is no reason currently why it should beaten by many of the others. Other groups such as Gabizon, Narang and a French group (Lyon) have also shown non-specific changes in urine.
• Chronix Biomedicals.  At the moment simply so little information is being released that it is impossible to assess.
• Roche's Infra Red plasma spectrometry system must be useful if we only knew why it worked or in what other conditions it became positive.  For instance, along with the TSEnse methods it must be good for confirming biochemical screening of  blood.
• Ante mortem specific tests: Blood tests
• Microsens Biotechnology has a good system shown to seek epitopes at a lower level than background noise. It is fully patented, and they have been fully funded for research. Again, they require a PrPsc separation scheme and antibodies with a high affinity. Certainly the PrP separation is now available to them  through an interesting designer compound they have called 'Seprion' and they are now putting together a second method to check their screening results. I am told that they can now seek positive or negative tests for PrPsc in <1ml blood  from sheep with scrapie early in the incubation period to the time of death. These findings make it not surprising to find Microsens Biotech discussing the full selling of their methods to major companies but no data is being given out about this.   It appears that their system would be good for testing large amounts of blood transfusion samples (at least for further assessment) or possibly cattle and to follow that up with a highly specific method.  Already they are testing blood samples for CJD in symptomatic patients. Their method now seems to be the most effective at extracting PrPsc from mixed samples, concentrating them and then looking for extremely small quantities.  At this point (2005) they have been approached by several large players.   The question is whether they can organise themselves adequately to make sure that their small company can gain from their amazing research.
• Neil Cashman.   The publication of the prion-specific antibodies by Neil Cashman may actually have the answer to Caprion's problems in looking for prions in blood but there is a lot of worry that his antibody will not be adequately specific and  have a high background noise to get around.  Remember that Cashman may not want to continue his former working with Caprion and take his antibodies elsewhere to be assessed.  No commercially potential results have been published.
• Adlyfe Inc test is interesting to look at but really it is not clear whether it will work in anything but brain contaminated blood.
• BioMerieux.  Their group has gone to various blood transfusion units and declared that they can test blood fro prions.  Nothing has been published (2005), and nothing has been submitted on their web site.  Everyone is wondering exactly what they are doing but they might appear from nowhere with the answer.
• Aventis test is basically involved in the improvement of the CDI test that was developed in Prusiner's lab in California.  There are basically no data published to show that the test is of use from blood but this is appears to be their direction and they are quite determined to chase that direction.
• Prion Developmental Laboratories also has been invested in by NASDAQ investment corporations. However their methods are not clear to me at present. Again, I think that the use of RNA fragments or individual antibodies are likely to be found to be inadequate. I also think that the development of PrPsc based assays by creating the peptide and producing competitive capture assays will probably not be sensitive enough. This may be the same way that Paradigm Genetics and Nen (Perkin Elmer) have come into the field.  They seem to be getting scientists together that would otherwise, in academia, be against each other.  Hopefully they will succeed, but I am not yet convinced that they can come into a field and understand enough to get things right first time.  However, their ability to work with these academic groups may mean that they will be ahead in some ways, and their contacts with the academic groups appear to be exceptional.  We are now quite certain that immuno-PCR will not be adequate when looking for the quantities that are small enough in blood and that PCR will be an expensive method to use to screen huge numbers of blood samples or tissues.   We heard nothing from them in 2004/5 (except for more money being invested in them) and the question is whether they are just being quiet or are backing out.
• Mary-Jo Schmerr's technique has been shown to work in scrapie in sheep and chronic wasting disease of deer. It has been rumoured that it might not work in BSE and in humans, but I am unable to confirm this at present. Mary-Jo has now left the field, and other groups are looking at methods of using her separation systems before high voltage electrophoresis (e.g. Inga Zerr, Gottingen) and they are having exactly the same problems with a difficult test that cannot so far be useful in humans.  At the moment (2003) the system seems to  have been extremely poor at even showing that there is any PrPsc in blood that can be separated and demonstrated. Currently this method must be looked on as unsuccessful but Mary-Jo's work was acceptable.  To some degree she feels a bit put down by it all.
• Gabizon's system for showing PrPsc in urine early in the incubation period in hamsters.  This is bound to be an exciting twist and this method along with one of the others needed to simplify the technique may well turn out to be the answer. The similar extraction method from Harash Narang, and from Prusiner (in his patents) must make Gabizon's work clearly valid but I do not know whether she will be able to retain the market.
• Serono's multiplication system will certainly require a powerful indicator system and I think that the necessity currently of doing this at Category 3 means that it probably can not be used to bring the infective agent to high quantities. Because of the necessity to avoid false-negatives in the screening systems that are needed for blood transfusion testing, I suspect that the current Western blotting and sandwich ELISA systems systems would probably not be adequate.  It now seems (2003) that Serono's system will be unhelpful unless they find an answer on how to get around using ultrasound (and yet be patentable) and the fact that other groups are doing the same thing.  Also their desparate difficulty in expanding the number of prions past a certain ceiling just seems to be impossible to get around...it as if there is some other factor that is needed to be present.
• SIFT  This seems such a good method to get around the background noise problems that it seems excellent if it was put with a system that was good at separation and concentration.  So far it can  be stated to be patented and will work well but without the other methods SIFT is not likely to succeed.  The method requires a concentration step in advance.

If the companies would just play game with each other...... There are extremely small amounts of a prion agent present in brain and an even smaller amount in blood.  What is needed is a concentrating step, that is selective but does not lose much of the agent in the sample.  Then an extremely sensitive but highly specific method is required to indicate the presence of the prions that have been concentrated.   Well all this would be possible if perhaps the concentrating step of Microsens was joined with the very specific and sensitive systems of SIFT, Prionics or InPro.  Perhaps the multiplication step of Serono could be used to allow the sensitive step of InPro a chance...and many more.  If only the companies would realise that by joining together in some way the problems would probably be solved.  It is becoming clear that the lack of interaction between the different groups and companies has to some way stopped the growth of the diagnostic test itself. For instance the determination by some academics not to permit other groups to use blood or tissue samples for testing that they have to assess their test is a major faulting of the system that should be stopped by official intervention.  The different inventors will have to realise that between them they have the answer but they must interact to get there.  Some companies may be hugely overestimating their ability in this one; e.g. Chiron have bought up the rights on a good monoclonal in prions..but this is certainly not all that is needed and it may take them some time to find this out.

The US test market for cattle?  The current worldwide market for BioRad's test is around $100 million and they expect that if the USA demanded similar testing for cattle then this would be a further £300 million.  At the moment BioRad is the biggest supplier of BSE tests in Europe.  The major problem is that its test, however sensitive because of excellent antibodies from CEA,  is complex, and difficult to mechanise without running risks of making mistakes.  Already they have mechanised the system but they may be too late.  The major players for the US market must be looked on as InPro, which was simpler than BioRad's test, quick (3-4 hrs) test, and Idexx, which has a rapid, simple, mechanised test, not requiring complex equipment.  Despite all Idexx's sales advantages (they are the biggest selling of veterinary tests in the USA) InPro is associated with Stan Prusiner with his Nobel Prize and this must be a sales factor.  BioRad may be present in the fight for the market initially but the sheer simplicity of the Idexx and InPro tests will either drive down their price or give them only a small part of the market.  Current claims by BioRad salesmen of Idexx test errors cannot be justified.  The Prionics test is good but it must be realised that it is complex and expensive; being recommended officially mainly to avoid their errors perhaps.  Probably it might be used as a secondary test if any test result by Idexx or InPro claimed to be positive.

Ante-mortem tests: the big prize.  The company that wins this will make the most money of all.  The fact that vCJD patients are young and give blood long before they had any symptoms of disease themselves means that we must be looking for a way to test blood.  At the moment in the UK it is simply not clear just how many cases of vCJD we should expect and numbers from hundreds to millions have been put forward in a reasonable manner to their official groups.  Also, as can be seen in the USA currently, if there only had been a way of checking cattle before all the problem appeared then the various farmers, and cattle traders would not be worrying.  At the moment it is not clear who is going to win this prize:

• Microsens' method to look for exceptionally small amounts of PrPsc and to concentrate them from blood is just shown to be useful then they should do well.
• Cashman's new antibodies can separate PrPsc from blood early in the disease: and exciting step but no clinical or commercial direction taken.   We still do not know which company is doing the best and we are relying on the UK Blood Transfusion Service to tell us (because they are comparing the methods).
• Gabizon's (and hence Narang's) method turns out to be repeatable by others then we should have no problem but the difficulty is that their results may be non-specific.
• It is not clear that any of the non-specific tests will be useful if the specific tests get going, but they may be of value in simply screening large amounts of blood (e.g. the Roslin Institute test)  but in my guess TSEnse's method, which can be used to follow the progression of the disease may, because of its simplicity and speed, may well turn out to be of value. Don't forget Proteome's non-specific blood test and Roche's one on the way: we still dont know where they fit in the market but they may certainly be worth chasing meantime.

Beware!!  Any investors should beware that simply because of the way in which the BSE epidemic built up in the UK (denied as requiring testing or treating by the UK Government) most of the researchers in the field, who started up the commercial side, are academics and as such may be geniuses but poor businessmen.  As a result of this to some degree we have seen a number of small companies coming into the field that are completely incompetent and yet asking the NASDAQ for funding.  They just use the word 'BSE' as a way to get the money and you must look hard at their evidence before making any investment step.

Dr Dealler is a consultant medical microbiologist and has invested in several companies involved in this field.

Return to index page

If you have any comments on this page, please contact the editor, Stephen Dealler, deal@airtime.co.uk

©Priondata.org UK 2002, All Rights Reserved.