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Guruprasad P. Aithal, Digestive Diseases Centre, University of Nottingham, Nottingham, Great Britain
Thursday, Nov. 1, 2018 · 6:51 p.m. · 39m 01s
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the title was very a interesting and challenging so i have focused on last
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five months of uh information i'm assuming you know everything before that
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might have a couple of slides just to tell you where the roots are but i genuinely have picked up a literature
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for the last twelve months about twenty seventeen to twenty eighty nothing else
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and i've taken some of our own work which is on publish so i mean i added them out before the uh the yeah the out
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um some which are presented market paper some which are under review from
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we're going to be presented in the a. s. l. b.
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and i've also taken some work which i think is important in the field from others uh so i'll i'll talk you through that
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so always make it move
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okay first of all i want really kind of um be up front with the
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uh with the definition of what i call going in his liver injury
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which is accurate onset liver injury activity to the medication in a therapeutic goals
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that is not predictable by its pharmacological action and so that is my definition of going into a little bit
00:01:10
it is not an overdose and i personally think that thinking more power to
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them or lower those isn't a distraction forty this incredibly windows loaded
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i've just been so for the so it's it's been so for clinical purposes well
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so the terminology soft feel typing crudely used uh but
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still have full and they seem to be unique uh which i'll show you some data for
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it's happened a cellular is predominantly a l. t. elevation called static predominantly l. p.
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elevation and mixed when that is the um combined uh elevation about and that
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i'll be talking one um what the gaps are and how big data
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epidemiology will probably improve our knowledge of a a pretty now you
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have begun to live in the which has been the biggest a battery of for us to even tell how common anything is
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i'll talk about um short and long term outcome which we
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have got a much more um uh information on
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i'll talk about what we have learned from g. was um and noble marcus
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and the program which is going to open the probably in january february
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and then i'll talk about treatment again all from the last yet so
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good going to lose a prevalence is really on on
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um other than one probably well done prospect do
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a study in the population level then in iceland value can know all the population by the name
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so that whole scene by three physicians in the country so my friend
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and i was managed to do a population based call for study
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but there isn't really otherwise oh anyway of really finding out other than going for a big
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data which is available so you'll case seem to have a clinical practitioners a data link
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this is start in nineteen eighty seven and it's got a longitudinal um population based data
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and also uh uh because it's national health service uh you will be able to link it
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even if the mood a towns because they have got one and it says number
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and but only difference from other countries with a light databases that about
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probably five percent of the population are um in this database
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so they're widely spread in the country but they're not that for every every primary kept track it's
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so since still doesn't chan the data has improved by linking it
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to possibly labs or statistics at all the data cancer registry
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and lab data which means that now we can do much more sophisticated
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a much more reliable piece of work and this is one of the uh studies which is published last year
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which eventually nail down the prevalence of one of
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the common drug induced limited the importance of
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trying to first of all tell whether drug is really related to a
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big signal is because regular got artist make decisions all the time
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to read the whole with drawl all really the send a while arms on this
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all the time it comes from what discourse point is reporting prowl the work
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and the reporting from spontaneous um methods is about two percent for all they
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can do that in the end ten percent force you just beginners level
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so we do not really a have hard data for someone
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to make a even a regulated decision making choices of
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what direction will give so this was one of the study which has got prescription data link to it
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so always sees if you see lots of registry data which are published in big generals that all caught
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which uh biased by bad they see the doctors and whether they get into the registry or not
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so the data is really a prima logically and sound we can learn from them in a different way
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so this was um a population based this that lather followed the prescription of the drug
00:05:15
and just to compare to drugs they took occidental cycle as a control and there's down posted actually
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flew clocks as an antibiotic has got higher likelihood of causing the the news louis and
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if you really uh look at other controversies that by that age user this factor not
00:05:34
and they've concluded that it was really increase lose by three four
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um compared to what uh at that age group so you can i just flick otherwise you will have to really go to the core
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database in seven we have made a lot of them are elderly but my dog of them and really always get the drugs
00:05:52
so you have no denominator which is really scientifically sound for it really calculate any of such data
00:05:59
but this is on publish date it was present at the in the abstract is one of my friend uh i uh causes whoopee
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was sent me a bit more updated data she haven't published it so they need to be sacked from your relates on
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which was the even bigger data we a has got very
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good database and they developed an algorithm really question it
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and they had nearly a one point eight million um
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prescriptions and they identified about eight hundred uh people
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who didn't have any problem about that
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is it me
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so this is not what i meant by factoring um so
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so they they had a large database and they don't appear rather than to
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quest to this database as you know me do adjudication of every case
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to several easy related roadblock that's another challenge but the device an algorithm where
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there could really look at you know shot description of two weeks
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they could put a a cut off by forty five days and found out
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how many had really trash short of begin to live in new reached
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and for those who had long the prescription they had a threshold um set
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up at about ninety days and then they uh design a longitudinal study
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of people who had that modified good into louis i'm had what happened in the end
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and this short or long term outcome which is very very valuable comes from the population database
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showing that they not only demonstrated that they didn't leave it in the uh
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prevalence but also the rate of people who needs that ten transplantation
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as well as long term outcome up to twenty four months two point five seven percent
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mortality so now we start having really meaningful reliable data on drug industry with it
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outcomes this is a paper from a large cohort study from america which showed that about
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ten percent of patients who are now biased cohort who come to the doctor
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directly into yes this is substantially more bit condition
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and you can see that about eighty percent of these are considered directly related to
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the drug induced liver injury or at least a secondary causes the gun disneyworld
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and they tried and find out what the buyer market far we have for beginners lovers
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you might know that is a a very popular a terminology used by regulator toward is quite high is low
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quite slow comes from observation by time of the moment we just said that patients
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will become don't based what would happen to sell a pattern of liver injury
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i have got a serious outcome about ten percent of the time and this has become
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almost like a gospel through and regulate your thirties for this very very strictly
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and they usually pick up people what would be little been elevation more than to talk to tom simply become normal
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and a l. television more than two income supplement of normal and look at whether there
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is problems of people meet high is a lot more in cases compared to controls
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and this is become almost like a a sub speciality in itself uh in have that already
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well this study showed that actually if you calculate properly you have to sell
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a pack of liver enzymes by looking at a l. t. elevation
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activity divided by l. p. aviation activity which is call now
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our biggest highs law is uh another a new term or use i am still avail t.
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you can still identify patients but much back uh who will develop a a
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fee via outcomes that that's a pretty active have had a failure
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the point is this observation just so just that happen to sell
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a pack normally within them is more c. via them that
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and the way to identify it much more european based way
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which is using in our value calculating that um
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uh have a similar pattern based on our value rather than going by what high describe nineteen seventy four
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now coming to some of our own work so when i started my p. eighty
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about nineteen ninety six first thing i did was read and find out that
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and other models are really of no use 'em in anything really and
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they are the reason why we have learned very little about
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the gun delivered is still used for regulatory purposes but um they
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do not really reflect a brooding does live under twelve
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so one of our our hypothesis was that drug goes
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through metabolic pathways and commonly generate reactive multiple like
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it's not uncommon at all even for the current breaks to generate director mike about
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but body has got really by activation processes which turns them into
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either stable megabyte or actually the acting what about very quickly
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if they still have got some the empowerment of uh
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um these processes or individual has got a susceptibility
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to either generate highly active multiplied by put uh uh to the park place
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or inability to actually them even produce higher level of reactive mike about like which might cost
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i the beginners limiting you know very very extreme circumstances but more
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often than not courses sub clinically which sends a danger signal
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but he acted like might either directly cause oxygen c'est ca some sub clinically injury
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or it might be buying to cellular also played in protein and the is really might
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really hard to sell a function or sometimes the function of other organs elsewhere
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these
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itself might really costello injury by arguing the function of the set than
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these cellular product yes taken up by the i didn't present itself
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and that really generated in the action and that is really cause of a good is limited
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in the meantime they're a feller adaptation process if you fall under the act multiple like
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that is into cellular processes which really protective from oxygen stress
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if you have got to a certain limited you label can
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recover if yeah buddy melinda spawns that is emitted talker
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so it's only when you are on the wrong side of the drug at several
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steps you actually get into that would interfere with the fancy phone call
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but our principal was that we will only tested it in a human way
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of course that are very difficult to really have human behave in an experimental standards
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but we taught that at least they're humans so you take
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a confounded as a uh as the um in the
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right species you might get to the like ants so you
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i don't really do always you might association study
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and use the robust methodology to identify
00:13:48
associations and see whether they come up with biologically plausible reasons for going in is limited
00:13:56
we did really initially find out that are drug specific
00:14:01
and class specific and genetic factors i showed you the ops events which are usually
00:14:09
before i'd like to to be drug specific jogger polymorphism in these obscene events
00:14:16
and you will get little dingy for both specific drugs
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because both specific part with have got really abnormalities
00:14:25
so that shouldn't they generate partway which really eventually
00:14:30
pretty exposes you to toxicity and kill now
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with all the long white association study we had done we hadn't really shown anything common
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but last e. s. you know might association study had about a thousand patients and we found that
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if you take away call lock sick level through clocks is only because that was confounding
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over results because predominantly patients all local what was full operation with colours clown folklore
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so we took them away so that we took away all they had chili singular they haven't really uh bringing out
00:15:05
we still found significant association with hatcher later to the oh so what have we learned from it
00:15:13
first thing is that i know i was really generally part ways which probably is related to add up to me and just wants
00:15:22
and they may not be necessarily depending upon
00:15:26
completely to the actually reminds although they're still necessary but
00:15:32
not sufficient steps to cause begin is limited
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outdated up some of the four top drugs which have contributed to be school park
00:15:41
where there is a strong association we had a little bit the or what
00:15:45
and find out how the final common part to works it'll come to indeed yeah
00:15:50
so these are the four bucks and i've got a structure that and you can't see any commonality between them
00:15:57
so if you look for common factors is that they're all like herbalist
00:16:01
in wonder about which means that the obscenely went far really
00:16:06
i said sure but not sufficient probably it really eh come up in that you
00:16:10
know might association study but they're still really part way which i mentioned
00:16:14
that you probably are going to palmer recommended like you probably going to format
00:16:19
that and then really uh haven't adapt human response um a trigger
00:16:27
so i'll show you some um ways we have really explode how you
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can really have just i tell association which might intricately related
00:16:40
to pad the genesis of going in and would it was twenty one year old student i saw a few years ago
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she had six this of the only this should just come back from holiday shared a boy
00:16:51
in the back and just describe the motors and chatted for one week and she's jaundiced
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and when she came she already had a nine i'm going up not reaching the trash or
00:17:03
because she had come from a holiday she had extensive investigation just exclude all the infection possibilities
00:17:09
and then eventually you she though look operatic failure share the transplantation
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about the same six months i the second patient
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fat a similar story he had gone to middle east this lady came from india
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he had a law degree of temperature he was also exposed to call mark subtler
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he also developed uh i could have added value and had a transplant
00:17:39
patients why don't transplantation from call most probably in six months
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well you know transplantation they'll it what i tell a although they don't use it
00:17:48
for anything so it's just a bit of a fashionable thing to do
00:17:52
and this is biopsy of one of the patient um which is trans juggler you can
00:17:59
see i like that sells here and the rest of it is just really
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collapse to a tissue that is normally with the left
00:18:10
same thing with the other patient same thing in the next one
00:18:14
is clear cut massive some massive macros is of the little
00:18:21
one of those patients had had tell a yeah the one one five or two
00:18:27
which is not that this factor which we had found in the genome wide association study which one file one
00:18:33
but both of these patients variations so if you look at
00:18:38
thing elliptical palm of them frequency had to lay
00:18:41
the i. b. one one file one is about uh
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most common a variant uh in a caucasians but
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one fly or two is about point zero seven so it's really less than one percent really
00:18:55
while it's about fifteen percent uh combinations so busy that newness
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factor and how does it differ from i tell a
00:19:07
one five o. one molecule is the question well how could both be this factors
00:19:13
for that you need to really look at the propriety binding rule that i tell a money so i've got really that too
00:19:19
they want to i don't really want to in two different
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ways and there's one key side in the pocket one
00:19:29
which has got one i mean i should change between one file one one point o. two one for
00:19:35
your one has got well in in the same place back it's dry scene for one file to
00:19:42
that that binding blue is the place where drug modified add
00:19:47
that comes in by use i needed to fit in
00:19:51
into the do what physically and electro chemically so if
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you look at the um physical um properties here
00:20:02
that is really fairly similar shape this is bad unless it is you might see from a distance there's a
00:20:07
a daily in here is ominously this so there is no substantial difference between the puppet binding though
00:20:13
this is a electro chemical uh uh properties of it so
00:20:17
if you just want to simplified um ladies acetate
00:20:21
louise outline i didn't see the uh pockets are really fairly similar
00:20:28
so the calls that electro chemical properties and physical properties or the pap that
00:20:33
by bingo especially pocket read two different amino acids are so similar
00:20:40
you could really uh have a similar risk profile with then genotype
00:20:45
which makes you think that packet binding who is the one probably deciding the binding
00:20:50
off it which goes back to my point that actually most common way
00:20:55
you'll get to begin to live in the east really by i that formation of the drug
00:21:02
so going back to slow clock to fill in his own published data you would
00:21:05
have seen this and they didn't takes the two thousand nine where we picked
00:21:09
up this little starting the sky it'd be more fun you do what you
00:21:13
know might association study this is a a tad for i tell a
00:21:19
the five seven o. one so this was eighty four
00:21:24
elevated it's p. value was minus thirty two or something so it increases the risk of look
00:21:30
look succeeded by eighty four in the first quarter and holder forcing the axle second court
00:21:38
we have done more work on the part by binding that once evil as i said before is it
00:21:43
the puppet binding mu and specific amino acids are don't determinant rather than just the dealer type
00:21:51
you probably know that five seven o. one is also this factor for about going hypersensitivity skin reaction
00:21:58
so but i have a good hypersensitivity eh really is mediated
00:22:02
to a little bit different mechanism which i'll come to its clark arthur grappled for
00:22:07
a mechanism so we want it the civil whether through clocks isn't it
00:22:13
determined a change in the and i put a lot of peptides
00:22:19
um is bound to this molecule but if you look on
00:22:24
pad the uh the other types when we did
00:22:27
this second analysis is also genome association study when we had more
00:22:32
patience and we found actually beyond the five seven or one
00:22:37
five seven o. three was also this factor which which you know my significance
00:22:43
so then what is the difference within five seven or one and five seven o. three is just one of the nice it's
00:22:50
which you have labelled three key awareness it see a whaling is a ninety seven which is the
00:22:55
mean ass but i guess it is one one one four and see in one one six
00:23:02
it's yeah we're changing the way too large in in your diet changes from five seven all the five eight or one
00:23:09
and neither flow clocks actually know all about going hypersensitivity
00:23:15
is related to five eight or one which means that way ladies
00:23:18
really absolutely he i mean unless it will slow clocks
00:23:24
hi plus a hypersensitive suppose i'm sure they did a little injury up
00:23:30
this but with five seven o. one as others fly so
00:23:33
no three bar that is it changes from seed into tightening which
00:23:37
does a basis less important for flow clocks is really
00:23:41
what about the hyper sensibilities not related to five so no
00:23:45
one which actually that actually i have a good hypersensitivity
00:23:48
is really not related to save interaction between the ad
00:23:52
that or the drug with the puppet binding though
00:23:58
so what we have learned from g. wife is that actually drug
00:24:04
interaction with titanium molecule is much more complicated than we assume
00:24:09
i started with the hypothesis is the standard partway value have got a a drug arthur pap drive
00:24:16
just take the byline didn't present itself presented to the t.
00:24:19
cells and the interaction between the correct title or molecule
00:24:23
correct protein and the t. cell receptor generate the interaction
00:24:29
but then i really i don't ways how high terror molecules can be the mediating
00:24:35
um reaction to use an activation one of them is hard pharmacological interaction
00:24:41
bad drug directly binds to the i tell it uh
00:24:45
and pepper binding do and stimulate the reaction
00:24:49
second one a third one is our target to talk on a compound
00:24:54
our target the problem model bladder drug goes and
00:24:58
sits in the a puppet binding do without
00:25:03
cold and you're bound to it and are to the shape of
00:25:07
the next to a space left in the piper piper bindings
00:25:11
which means that the normal proteins which have got a shape which would not have bowed to the
00:25:16
pocket binding little in the normal circumstances no that is the other person in the bad
00:25:22
so different shape applied which is no multiplied and uh just apply can't bind and generate reaction
00:25:30
which brings me to that next patient whose eighteen year old male
00:25:35
who uh presently jarvis so his stories really interesting almost like speaks of all twenty two
00:25:40
packets so he actually see directly so he was prescribed right america as it
00:25:46
which is the first line medication for acne didn't work so you've given my most likely
00:25:51
he began jaundiced has got a in a which is high idea is high s. m. is positive
00:25:58
and is bob seashells portable track is completely destroyed
00:26:02
with informative cells blast muscles excluding outside
00:26:07
so this was diagnosed last argument for guidance and someone
00:26:12
started a mostly whites and what acne so the
00:26:17
patient was gonna disease you fade to treat it by one but you my mother dread human disease
00:26:23
and then three that this is that you have given and you is this is back so it's kind of a trial and error of madison
00:26:31
but the lessons from him is that he had um i tell a bean five three or two
00:26:39
and if you want to tell a bar fight to a file at the fire or two
00:26:43
just caught the docking experiment you can model the packet binding
00:26:47
go and see whether the molecule directly six it
00:26:52
these are good i forgot complex you can see both the today and that really like them and there are lots of calculations
00:26:58
you need to do it in the computer i'm not an expert but i am reliably told that it does what
00:27:04
so you have got about that but the girl had got something sitting in it so if you live in the low will put up tight
00:27:11
which has got a shape which would have fit in on top of it
00:27:15
would not have wanted it's logical had it not been half occupied
00:27:20
so this is uh what is called a wider was three actions
00:27:24
it's like they get cause walking on a glass wall
00:27:27
so these are physical uh actual not calling binding or any binding actually they just sit and there
00:27:34
are to the shape of the puppet binding though i make normal peptides bind and then generate
00:27:40
so that it is important but but kind of drug is also important
00:27:45
and how we didn't actually actually is what we have learned by studying this
00:27:50
so what is the application of so this is a uh one of the um
00:27:56
facts of all ugly compact is we need to see if you think of
00:28:00
anybody comes available and rams five times or three comes up look of
00:28:04
normal i'm sure most of the hamper dollars we'll all do a they
00:28:08
f. m. a. i. d. d. l. k. on all of them
00:28:12
and one of the ways of looking at how these caspar form is really say well
00:28:17
how many of normal people imported into it and how many patients
00:28:21
with drug uh individual condition will be positive about it
00:28:26
and if you look at the the genetic tests that got similar performance
00:28:31
characteristics similar to the test what you do all the time
00:28:37
if you look at um a in a in patients all forty about
00:28:42
twenty four percent will be positive or even given the title that
00:28:47
and if you go but i. d. s. m. any if you don't do really i mean
00:28:50
to act in a specific it'll be that in forty three percent of the time
00:28:57
and these tests are easily available can be done
00:29:04
and there are several uh drugs i would say about twenty blocks
00:29:08
rather high tell a a a associations i really found
00:29:12
and they can have a very good negative predictive value that negative
00:29:17
predictive value generally over ninety five percent most of the times
00:29:21
so you can use them to really explore we're going to the body when someone
00:29:26
need to be on a white light seven bucks antibiotics are very pressure
00:29:30
and applet curves are quite precious auntie to butler box in most of the countries are very very precious
00:29:36
so you don't really necessarily need to uh take away the draw
00:29:40
when the suspicion is what you go by to stop that
00:29:45
and many circumstances they can actually support the diagnosis because of the
00:29:50
you use a therefore supported diagnosis estimated for supported likenesses they're no different
00:29:57
and i don't have a kite is the the paper which is published i'm not really fighting it here but it's in
00:30:03
a little international also last year which showed that about all the patients in you get agnes vitamin a packet
00:30:11
only to to hurt me international uh um criteria for
00:30:17
automatic right of which be that we as
00:30:19
you it's easy to diagnose but it isn't and d. r. b. one one file one
00:30:27
is really last represented in the ottoman appetite is while zero three zero one and zero four zero one
00:30:33
on really more represent an automatic i get an argument
00:30:37
appetite is original scoring did include genetic testing
00:30:41
so you can easily tell what the patient who had gotten acne to get this to you right back
00:30:47
uh by doing such tests that's that's a kind of application
00:30:52
in my system it cost me thirty five pounds to do i
00:30:57
teletype high resolution five seven or one four four digit one
00:31:03
while all the specific antibodies you do rampant lee about a thousand times the uh
00:31:07
cost about twenty one pounds so there isn't really any need
00:31:12
for us to look these tests that's all that precious
00:31:18
totally to the data which we haven't published even more generically this is the paper which will
00:31:24
be present in a sunday we now have got larger data set between us in america
00:31:30
and this is the first non h. l. a. g. n. h. which has been associated with the good as leverage to
00:31:39
this is a a track for p. g. p. n. twenty two
00:31:43
which is a molecule which uh has got a key role in regulation of a t. cell activation
00:31:51
and beefy condition for i tell a molecule it'll still be
00:31:55
positive which we that is not willing to italic
00:31:59
important thing is that the j. p. n. twenty two is
00:32:02
a social type one diabetes targets causes a details disease
00:32:06
a remote or arthritis and some of the ottoman diseases which brings back to the hypothesis that actually
00:32:12
e. t.'s uh uh an adaptive immune response which
00:32:16
is key to probably begins with the susceptibility
00:32:21
and i just put it up this only slide which is from the past i had
00:32:26
draw only slide in two thousand four when i was giving a talk on
00:32:30
bike lovemaking do limited just to say that how signs comes around
00:32:35
so at the time we had this hypothesis and we're looking
00:32:39
at vital kind polymorphism really demonstrate whether they're susceptible
00:32:45
i just told you about uh um the p. d. p. n. twenty two
00:32:50
this is the staff maddy taps so if yeah but i didn't present things out which binds the t. cell receptor
00:32:57
activation and proliferation of t. cell depends upon the sideshow kind in
00:33:02
wonderment and regulate the circumstances under which it it works
00:33:07
so if the debian twenty two it's function uh is to really regulate the cell signalling
00:33:14
it has got number of proposed uh activities but
00:33:17
overall it almost like influenced before step
00:33:22
of really t. cell activation and then some of them might be th
00:33:27
to part ways some of them might be catch one part they
00:33:31
true clock for example might be directly related to a faculty itself but
00:33:36
we have taken about fifteen years to get to this point
00:33:42
finally or what we're going to do um these two
00:33:47
in a invest in trying to double up now
00:33:50
circulating while marker a discovery to diagnose um
00:33:55
the game is limited that's another gap we have got is one of
00:33:58
the uh glance funded by the i think i am my
00:34:03
which uh i came up with this only pay per uh just uh uh d. c. uh
00:34:08
the the program was called safety but that actually safety by marcus they came up with his algorithm
00:34:15
that if you have got patients so i've got to intermediate level of null
00:34:20
below their safe about their like you'd have transplantation you side to get it in eighteen
00:34:26
you might get some sense of it is that the data programs to mark
00:34:32
and one of the data which was not published in that paper which i had access to
00:34:37
shows that if you look at specific group of patients with within his liver injury
00:34:42
mac fate colony stimulating factor receptor one circulating levels last distinguishing
00:34:49
have a pet sitter marlboros a. p. a. p. toxicity from brigade of love it
00:34:55
that is a diagnostic mark that is not things all i
00:35:00
know off which really picks that up body distinctly different
00:35:04
is the point i was trying to make it that a. p. l. p. talk city
00:35:07
isn't really begin to live in the yeah any sense which i can see
00:35:13
there are really eh uh attends really try and find my colour profiles which might be
00:35:19
related to good individually and this is the very small study which shows some
00:35:24
a positive or negative signals uh but this is not validated but i just want really
00:35:30
bring you the the i am i gonna reaches be now passed
00:35:35
we are going to the negotiation phase which means that we just need to sign the agreement
00:35:41
this plan to uh will allow us to look at the good of loading the i
00:35:45
read other logon injuries uh but been eluding these the biggest uh uh what package
00:35:50
and some of the bile marcus which we have chosen to investigate the the candidate by marcus
00:35:56
uh but the the story might change depending upon what else we discovered in between
00:36:03
we will be looking at michael i'm a profile to next generation sequencing as a a potential market
00:36:10
and we will be doing mainly in the phenotype using a site off which
00:36:14
is uh almost like a hybrid of course i commit mass spectrometry
00:36:20
and just really touch upon your top that bile acids are really part
00:36:24
of the bile market profile which are looking at mechanistic like
00:36:28
finally what is the update on treatment i just for the hard of of giving treatment with
00:36:33
this device for people what acne as well or even if they had played individually
00:36:38
uh this is one of the well to a one paper and one letter which has been published this year so
00:36:46
i define that would be really within the ass something which is not predictable by non pharmacology of the
00:36:52
drug so when i give a talk some other time somebody asked what about checkpoint any with this
00:36:57
i surely checkpoint any because i also act on the first step of i didn't
00:37:01
present itself binding to uh uh uh reacting to the t. cell receptor
00:37:06
and these are some of the signalling partners with the
00:37:08
determined t. cell activation but their efficacy is walk
00:37:16
does not seem to correlate with do deliver it so i don't think
00:37:21
that mechanism is so easily straightforward something like an ottoman hepatitis
00:37:26
and this is an additional uh on a data to conform that
00:37:31
also the method that everybody who have got immune mechanism underlying it uses device nor
00:37:36
do they respond to it so these are two papers one of them really
00:37:40
describe the prevalence of hardwood invisible in the from checkpoint innovator and showed that
00:37:46
substantial proportion i think in that group one third of them just wanted
00:37:50
improved so you don't need to necessarily dish out a lot
00:37:54
the trials i designed by on colleges without asking any applicable disappear which means that them
00:37:59
got in the protocol to give them extraordinary goes as of a stable it's
00:38:05
double check it was the latter which also conform that fifty percent of the
00:38:09
patients responded without any still ice and ironically goes to get the right
00:38:15
responded later than those within gets it right so you might even really ruin not just the drugs in fact
00:38:23
you remember that if you're trying to give any middle modulator to control the cancer and you give them still wide
00:38:29
you might and do some of the facts which yeah you already a done you might also early in the uh improvement
00:38:36
in begin to live with i'm not saying well this is categorical but it's important information for us to know
00:38:44
i think that's all i was going to say in the last year ah papa
00:38:49
that was enough uh for us to learn from this is my to you
Conference Program
FXR/FGF19 gut liver axis – new therapeutic strategies
Antonio Moschetta, Department of Interdisciplinary Medicine, Aldo Moro University of Bari, Bari, Italy
Nov. 1, 2018 · 6:04 p.m.
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