00:03hello and welcome to the quarterly
00:05webinar of Parkinson's disease brought
00:07to you by pure Parkinson's the Journal
00:09of Parkinson's disease and the
00:11University of Edinburgh my name is t
00:13Luna from the center for regenta
00:15medicine and I'm dialing in from
00:16Edinburgh Scotland today we have a very
00:19special webinar topic that's close to my
00:21heart stem cells so during this webinar
00:23we'll hear from Rachel Gibson a person
00:26with Parkinson's and a patient research
00:28advocate Cheney Drew from Cardiff
00:31University working on the patient
00:33experience in clinical trials for
00:34Parkinson's with a focus on surgical
00:36trials and from the University of
00:38Copenhagen agneta Kirkby a world expert
00:41in the application of stem cell research
00:42for Parkinson's and she's currently
00:44leading the clinical trial stem PD that
00:47we're sure to hear lots about so first
00:49we're going to go through some brief
00:51introductions from from each of the
00:53participants and I'll let um Rachel
00:57start hi my name is Rachel Gibson I'm
01:00I've had Parkinson's disease for 16
01:03years uh and during that time I've had
01:05DBS surgery deep brain stimulation
01:08surgery about seven years ago um I'm
01:11particularly interested in research of
01:14new Parkinson's drugs because I used to
01:16be uh before I was um before I had
01:20children I was a research nurse for
01:22chemotherapy and um drugs so there are a
01:25lot of new drugs out there for cancer
01:28patients and I used to SP spend quite a
01:30lot of my job uh designing the trial
01:33consenting the patient and giving them
01:36chemotherapy and now I have Parkinson
01:39I'm quite Keen for new drugs to come up
01:43uh to help slow stop and even reverse my
01:49you thanks Rachel thank you very much um
01:54please thank you hi uh my name is chany
01:57Drew I'm a senior research fellow um
01:59working at the center for uh trials
02:01research at Cardiff University um and I
02:04spend my time designing developing
02:06managing clinical trials specifically in
02:08neurogenerative diseases um with a focus
02:11on trials that include um advanced
02:14therapy so cell and Gene therapies for
02:16for neurogenerative disease and as um T
02:19said I've been uh recently undertaking
02:22um some research into the participant
02:25experience of people with Parkinson's
02:27who go through these complex clinical
02:30and see if we can understand how to make
02:32them better for people with
02:34PD fantastic thanks thanks Cheney and uh
02:39agneta yeah good evening my name is
02:42agneta Kirby I'm on this call from
02:46Sweden I'm a stem cell scientist and
02:49associate professor at Lund University
02:51in Sweden as well as University of
02:53Copenhagen in Denmark just across the
02:55bridge um and I've been working for many
02:59years years together with colleagues on
03:02using stem cells to generate dopamine
03:04neurons as a stem cell therapy for
03:07parkon disease and after many many years
03:10of testing these this cell therapy in
03:14animal models we have now succeeded in
03:18getting authorization for clinical Tri
03:21and we have transplanted the first
03:22patients in Sweden with this cell
03:25therapy um this year in February of this
03:29year so I'm very happy to be here
03:31tonight uh to accept any questions that
03:36have fantastic you know it's very
03:38exciting times um so let's start um
03:41right at the basics so get everyone on
03:43the the same page so agneta if I can ask
03:45you um if you could just describe what
03:48are stem cells where do they come from
03:51and why are so many people excited about
03:56Parkinson's yeah so I think the first
03:59thing that I'd like to make clear is
04:01that stem cells can be many different
04:03things so when you hear the term stem
04:06cells that can mean many different
04:09things depending on what type of stem
04:11cell it is so there are many different
04:13types of stem cells and they certainly
04:15don't do the same thing so stem cell
04:19therapy doesn't mean one thing it means
04:21hundreds of different thing and every
04:23single stem cell therapy is specially
04:26designed and specially made for one
04:29single disease so that's important to
04:31remember when you hear about stem cells
04:32in the media so we do have stem cells in
04:35our bodies we have stem cells in our
04:37blood they make blood every single day
04:39we have stem cells in our intestines
04:41they make intestinal tissue every single
04:43day these are very good stem cells in
04:46our adult bodies they're very functional
04:48and they're functioning functional our
04:50entire life but the brain doesn't really
04:53contain stem cells tiny tiny population
04:56but they're not very functional they
04:58can't really repair the brain so when we
05:01talk about stem cell therapies for the
05:03brain we have to go in and use other
05:05types of stem cells that we don't have
05:07in our adult bodies and in the case of
05:11our research and many other researchers
05:13in the field we use this special type of
05:16stem cell called the embryonic stem cell
05:19or the pur poent stem cell which comes
05:21from this very very earliest time point
05:25in development actually just after the
05:28egg has been fertilized by the sperm um
05:31and these stem cells you can get from
05:34IVF clinics um where egg and sperm uh of
05:39course is used every single day for
05:43fertilization and here you get these
05:46very early fertilized eggs and some of
05:48these of course are used for
05:49Reproductive uh therapy but many are
05:52discarded every single day and these uh
05:55Surplus fertilized eggs can then be used
05:58for research and these uh fertilized
06:01eggs can give rise to really special
06:03stem cells this is what we call the
06:05embryonic stem cells and what's so
06:07special about them is that they come
06:09from this early state in development
06:11meaning that they can they have the
06:14potential to generate every single organ
06:16in our body so we have this very special
06:20cell stem cell that we can culture in
06:23the lab and then we can actually
06:26generate every single cell of the body
06:29dep depending on how we treat the cells
06:31and that's of course fantastic because
06:34that means that we can make also nerve
06:37cells uh nerve cells that we can't
06:39normally make in our own brains uh so
06:43that's why we're so excited about these
06:45embryonic or Chlor potent stem cells
06:48because they have the potential to
06:50generate new nerve cells and that's why
06:52we can use them to make new cells that
06:54can potentially then be used to
06:56transplant back in and repair the brain
07:00um and they can also be used for other
07:01diseases like type 2 diabetes for
07:03insulin producing cells or
07:06cardiomyocytes for heart failure for
07:09muscle cells for uh muscular destrophy
07:12and many other diseases so that's why
07:14there's this uh General very high
07:17interest in these plur potent stem
07:20cells fantastic that was very clear so
07:23in terms of Parkinson's um in the
07:26simplest terms possible how would you
07:29Des describe a cell replacement therapy
07:31and how has that led to stem PD the
07:34current trial that that you're running
07:36yeah so when we talk about a cell
07:39replacement therapy so a cell
07:40replacement therapy is basically a
07:43specific type of stem cell therapy and
07:46when we say cell replacement therapy we
07:48mean that we actually go in and replace
07:52that particular type of cell that has
07:54been lost in the disease and when we
07:57talk about parkon disease we're focused
07:59here on the dopamine neurons because we
08:02know the dopamine neurons are the ones
08:05that are responsible for the main part
08:07of the motoric symptoms um of the
08:10disease so when we say cell replacement
08:13therapy what we do is we make new
08:15dopamine neurons in the lab from these
08:18stem cells and then we transplant those
08:21into the brains of the patient so we're
08:24literally replacing those dopamine Ur
08:27that lost because our own brain cannot
08:29make new dopamine neurons um once
08:34lost great fantastic so finally um what
08:40briefly there's a lot to say about stmpd
08:42but could you just describe the trial in
08:45brief terms and how is it similar to or
08:48different from any ongoing
08:50trial yes so um we started a trial this
08:55year in February called stampd and
08:57stampd is the name of the Cell Therapy
09:00product the cell replacement therapy and
09:02stamp consists now of stem cells that
09:06have been um cultured in the lab and we
09:10have treated them in a very specific way
09:12with a very specific combination of
09:14factors to generate dopamine neurons in
09:18the lab we actually generate very young
09:20immature dopamine neurons and then we
09:24transplant those into the brains of uh
09:27parkson's disease uh individuals with
09:29Parkinson's disease um this is a very
09:32new technology um this is the first
09:35trial in Europe with this type of
09:38Technology uh but there are two other
09:40trials ongoing in the world there is one
09:42trial in Japan in Kyoto that started in
09:47uh 2018 and then took a while to
09:50complete all the transplants of the
09:52patients and we still don't have data
09:54from that that it's going to come later
09:56this year uh with a similar type of
09:59uh but produced in a little bit
10:02different way there's also always these
10:03tiny differences in the way that you
10:05produce the cells in the lab but the
10:07concept is the same you make dopamine
10:09neurons from stem cells and you
10:11transplant those into the brains of uh
10:13individuals with Parkinson's disease and
10:15there is another trial in New York uh
10:18that just reported onee safety data from
10:2112 patients with a similar type of
10:24product uh showing that this treatment
10:26is safe and from what I've heard they
10:28will proceed into a phase two so these
10:31are the three trials that are ongoing at
10:33the moment and we are running now the
10:35European uh version of
10:38this great very very exciting so I'm
10:41gonna ask uh Cheney a question I'm not
10:43sure how familiar you are about this
10:46stemy trial but in general how do how
10:49would you do you view the consent
10:51process for these types of Trials so
10:52these quite Advanced trials a gene
10:54therapy or self therapy as compared to a
10:57standard say drug trial so how would you
11:00uh consider the consent process and how
11:02would it differ sure so for as anyone
11:05who's Taken part in research will know
11:07it's really important then when
11:09participants are approached to take part
11:11in research that they are given the
11:13opportunity to um ask all the questions
11:16that they need to and they need to make
11:17what we call an informed decision so
11:20they need to have all the information
11:21available to them about potential risks
11:24and benefits of that treatment or that
11:26therapy that's being investigated it's
11:28also really important to say we do
11:30clinical trials because we don't know if
11:33that therapy is going to work in people
11:35and this is the only way that we can be
11:37sure so people need to be um able to
11:40make an informed decision they're given
11:42a lot of information um and then they
11:44make that that choice on a on whatever
11:47factors are important to them so it's
11:49really important for these cell and Gene
11:52therapies that are are coming through in
11:54development now and into clinical
11:56testing um they differ from traditional
12:00drug trials in that they're are kind of
12:03One-Stop option um once you've had a
12:06cell or a gene therapy put into your
12:08brain you can't have it taken out um and
12:11so this may preclude them from taking
12:14part in other trials in future
12:16potentially benefiting from from um
12:18other therapies so there's a lot
12:22potentially a lot more to to gain but
12:24there's also on the flip side
12:25potentially a lot more to lose it's
12:27really important that we make sure that
12:29our participants truly understand what
12:31it is that they're signing up
12:35to great um so what um actually can I
12:40ask Rachel a quick question what are
12:42your thoughts so far on sell replacement
12:44therapy after hearing hearing what how
12:46ignet has been describing
12:49it uh I think I think she's right new
12:52chars we've got to give it a go because
12:54we're never going to learn anything if
12:56we don't and things aren't going to
12:58progress but um some trials obviously
13:02are easier to recruit I think than
13:05others um and my particular
13:09um interest in this sort of trial is
13:13that you have to have or ideally you
13:16would have two arms the placebo arm
13:19which is um a sort of arm that you don't
13:23you get the same procedures but you
13:25don't get the active drug um and then
13:30arm uh and obviously if that's a tablet
13:33taking it's very easy and you wouldn't
13:36really have too much discomfort from
13:38that um too many questions I shouldn't
13:41think um but obviously if we're looking
13:43at stem cells and injecting them into
13:46the brain the placebo arm could have the
13:50same procedure and just have salty water
13:52or something given it instead um and I
13:57guess as long as the the consent
14:00is uh can the patient who consent is
14:03aware of that then that's
14:08um is it fine is it fine would you sign
14:10up for a trial a surgical trial where
14:13the placebo arm is salty
14:16water well I think that's really
14:18individual isn't it but I personally
14:21probably wouldn't but um but then if
14:25nobody does then we'll never know if it
14:27works so um it's a it's a really
14:31important consenting process I think a
14:36this thank you I'm gonna ask comments
14:38from both ageta and Janie on that so
14:40aneta what what does the placeo arm look
14:42like moving forward I think stmpd is
14:44open label but what does it look like
14:46moving forward yeah I mean that's a it's
14:49a very interesting question you opened
14:50there Rachel and something we discuss
14:52almost at every single meeting we have
14:54and there's no consensus in the field um
14:57so the classical clinical trial approach
15:01is as you say you would have a placebo
15:03double blinded control and this works
15:06very well when it's an it's a pill
15:08you're testing for instance it's much
15:10more challenging in in a trial like this
15:13because ethically you would be
15:15subjecting half of the patients to a
15:18sham surgery a rather long surgery you
15:21anesthesia you would inject saline but
15:24on top of that you would also have to
15:26immunosuppression because that's part of
15:28the TR um we don't I
15:32mean personally I don't think it's a
15:35ethically um a good solution to do it
15:39like that because it is quite a lot to
15:41ask for patients and not giving them a
15:43treatment uh we do believe there are
15:45other ways of solving this large control
15:48groups for instance longitudinal
15:50followup along um roll into the trials
15:54you know the history of the progression
15:57for each patient which gives you you a
15:58good control group and then you can use
16:00in secondary readouts such as pet uh
16:03flopa pet which is not affected by
16:05Placebo uh to support your conclusions
16:08of the um of the clinical data it is a
16:11very difficult question and there's no
16:13agreement in Sweden they're not happy to
16:16approve a sham surgery control in the US
16:19they very much like it so it's also
16:21something that the different regulatory
16:23authorities don't agree on but I do
16:25think it's something we have to discuss
16:26with them because as we're getting more
16:27of these comp therapies Gene therapies
16:29cell therapies where a sh sham surgery
16:32control can be ethically contentious I
16:34think we need to find alternatives to
16:42um what I what ageta said um to a large
16:46degree um uh it's it's very ethically
16:50contentious the use of um what we call
16:53Sham control arms where a surgical
16:55intervention um is needed so one of the
16:59problems is that um uh where we talk
17:02about sham surgery um there are
17:05different it's what how far do you take
17:08that sham surgery um so if you're going
17:11to be a true control for your transplant
17:15as ageta said you'd want to do all of
17:18the things the same including putting a
17:20needle into the same Target area and
17:23injecting um a a very similar fluid into
17:27that area but not including the cells
17:31however most of the Sham control trials
17:33that are are going on at the moment um
17:36mostly for gene therapy and as Anette
17:38said in the US the Sham surgery stops at
17:41the level of um drilling bur holes into
17:44the skull so that's where you make an
17:46opening in the skull in order to um
17:49introduce your needle into the brain
17:51essentially um so at the moment most bur
17:54holes most sham surgeries only drill
17:57partial thickness bur Hol holes so they
17:59don't go all the way through the skull
18:01um but is that really a true control for
18:04your intervention there are also other
18:06methodological ways in trial design um
18:10that we can so the point of a a sham
18:13control is to reduce the amount of what
18:15we call bias um in your outcome
18:18measurements so how we test whether that
18:21therapy is working and so if if people
18:24don't know and the people administering
18:25the treatment don't know you reduce this
18:27bias if they um if they don't know if
18:30they're they're receiving the therapy or
18:31not as I agnetta pointed out you can do
18:34that with using other methodologies so
18:37stmpd uses a trial within a cohort
18:39design rather than what we call a two
18:42arm parallel design that most people are
18:44used to so you've got two very equal
18:46groups um you can use um uh a a biased
18:52randomization so more people get the
18:55treatment than Placebo um and various
18:57ways so it is very ethically contentious
19:00um and there is a lot of discussion in
19:02the field both in PD and other
19:04neurogenerative diseases um and advanced
19:06therapies about how we manage this
19:09issue yeah it's very complicated so the
19:12comments are coming in about this um
19:14maybe ageta can address one of them
19:16someone Louise has said can we use match
19:18controls like they do in the exercise
19:23groups uh yeah I guess you mean uh so
19:27you have a control basically for each uh
19:29patient that's very similar and and Ian
19:32definitely that would be the aim that
19:34you try to standardize your control
19:36group and your treated group as as much
19:38as possible I think there are many
19:40different possibilities the big thing is
19:42we need to get the regulatory
19:43authorities to agree uh to one of these
19:46because of course the placebo control
19:47double blinded trial has for so many
19:49years been the standard so it takes time
19:52to get them to to uh to convince them
19:56that new types of designs maybe is the
19:58way to go for these very complex
20:00therapies I also I mean I'm I it's I
20:04think it's interesting Louisa also
20:05writes as a person with Parkinsons I
20:07would never let you cut my brain open
20:09with a placebo I think you know that's a
20:11very important thing to say right we
20:13need to listen to the patients here and
20:16uh if the patients really think that
20:18this is completely out of the question
20:20of course we can't do this I mean we
20:22have to we have to take that into
20:24consideration consideration and also
20:26tell the regulatory authorities about
20:27this yeah I think you you said it spot
20:29on there aneta um I'm going to come back
20:31to the stem PD some of the questions are
20:34coming in about um exclusion or
20:37exclusion so someone has written um that
20:40a potential exclusion is Tremor dominant
20:43and then someone else is written into do
20:44I have a pink I have a pink one mutation
20:46am I uh eligible so what are the
20:49inclusion exclusion criteria for stmpd
20:53stands uh yeah so the inclusion criteria
20:56is that you have had to have have
20:58Parkinson's disease you have to be
21:00diagnosed with Parkinson's disease of
21:01course and you have had um to have 10
21:03you have to be 10 years into your
21:05disease but still at a moderate stage so
21:08AAR stage two to three in the off State
21:11um the age criteria is between 50 and
21:1575 um and then an important criteria is
21:18also that uh the individuals have to be
21:20responsive to dopamine nergic treatment
21:23because if not we we expect that they
21:25wouldn't respond to the stem cell
21:27therapy either so these are the main
21:30inclusion criterias there are lots of
21:32different exclusion criteria such as um
21:36overt dementia symptoms or Contra
21:39indications to neurosurgery or severe
21:43disas and of course it this doesn't
21:45necessarily mean that a larger Patient
21:48Group couldn't be eligible for stem cell
21:50therapy later on in the process but you
21:52always have to choose pretty strict uh
21:54criteria for your first trial to make
21:56sure that your patient population is
21:59relatively homogeneous because these
22:01trials are small in the beginning we are
22:03only transplanting eight patients here
22:06uh so it would be too much of a
22:07confounding effect if the patient
22:09population was very uh variable so this
22:13is simply the reason why uh we also
22:15exclude Tremor dominant disease I could
22:18see there was a question about this in
22:20the Q&A um one person asks um does this
22:25mean that people with Parkson disease
22:27who are Tremor dominant won't be able to
22:28benefit from stem cell replacement
22:30therapy and again that doesn't mean that
22:33in the long run uh the reason we've
22:35excluded Tremor dominant uh type of PD
22:39here is because in some cases Tremor
22:42dominant disease can be caused by a
22:46pathophysiology it's not always as
22:48responsive to dopamine treatment um as
22:52is to the same degree as rigidity for
22:55instance um or brainia so so this is the
22:58reason we have uh chosen to exclude the
23:02the very Tremor dominant disease but in
23:04the long run this could be included in
23:06in later stage trials yeah I think it's
23:08important to say that the criteria as I
23:11heard at a conference usually expands
23:13quite a bit after the first trials so
23:15DBS there's a couple questions about DBS
23:17is that an exclusion
23:20criteria yes that is an exclusion
23:25yeah um and then a question I was going
23:28to ask you anyways but someone has also
23:29asked it so um if the current stemp
23:32trial is successful how far away do you
23:35think the this treatment could be
23:37available for UK or Sweden sufferers
23:41through the Health Care
23:43System again probably get that question
23:45a lot yeah and it is a very relevant
23:47question a very good question uh the
23:50thing is these trials are quite long
23:52because we have to wait for the stem
23:54cells to we transplant them and then we
23:56have to wait for them to mature the
23:58nerve cells they start communicating
24:01with the patient's own brain cells and
24:03this takes a while and can actually we
24:05know from experience can take up to
24:07three years before the stem cells are
24:09completely mature I mean think about it
24:12a newborn baby it also takes a while for
24:15the brain of a newborn baby to mature um
24:18and and that actually can take you know
24:20up to 20 years before our brains are
24:21fully mature and it's almost the same
24:23process that the stem cells are going
24:25through when we put them into the brain
24:27they have to go through this maturation
24:29process that they go through when we're
24:31born uh that's why it takes a while so
24:34actually the efficacy readout of the
24:36trial is three years and since um it's a
24:40requirement that you have three phases
24:42of clinical trials you have phase one
24:44where you test the safety and that's
24:45what we're doing right now then you have
24:47phase two which is a little bit larger
24:49trial you include more patients and you
24:51look for signs of efficacy and then you
24:54have phase three with a larger patient
24:56population where you want to establish
24:58for certain is this efficacious and is
25:02it statistically significant and how big
25:04is the treatment effect and since each
25:07of these trials the phase two and the
25:09phase three each need to take three
25:11years and we're right now in the safety
25:13trial which takes around two years in
25:16total it will take around 8 years to
25:20trials yeah I'm sorry it takes so long
25:24but that's that's the way it is we have
25:25to go through that route yeah
25:28understand um I'm going to come back to
25:29DBS in a moment but just just to really
25:32answer one of the questions about pink
25:33one and park and and maybe DJ one these
25:36autosomal recessive young onset
25:39Parkinson's is is some with a mutation
25:42in one of these genes are they excluded
25:43or included or do they not check for
25:45these genes yeah we neither exclude nor
25:49particularly include them so you
25:51wouldn't be excluded if you have a
25:52genetic PHA praus disease we don't
25:54screen the PD patient so actually it is
25:56possible that we have individuals in the
25:58trial with a genetic form um of
26:01Parkinson's which we don't know of
26:03because it's not an inclusion or
26:05exclusion criteria as long as you fit
26:07into the disease duration of 10 years
26:10and the age U span of 50 to 75 years
26:13then you can be included yeah okay that
26:16that's clear so I'm going back to DBS so
26:18Rachel I can't remember if you mentioned
26:19but you you've had DBS um and so that
26:24means at the moment you would be
26:25excluded from this trial so when when
26:28you had DBS were you given a heads up
26:30that you might be likely excluded from
26:32future trials and what are your thoughts
26:35that yes I was um so DBS is well
26:39certainly when I had it seven years ago
26:41there's quite a lot of preparation that
26:43goes into it um just to see if you're um
26:46likely to respond so you have to have um
26:50similar uh um similar test to check that
26:54you're still dopamine you still use
26:56dopamine um there's quite a lot of
26:58psychological testing memory testing so
27:01it's quite it's a three-day procedure or
27:04it was when I did it anyway um and so
27:09you really are are given the opportunity
27:12to talk as well about anything else it
27:14you know do you go for DBS or is there
27:16anything else you could have um
27:19certainly at the time I was um talking
27:22about having DBS it seemed to be the
27:24most sensible option for me there
27:27weren't any forthcoming trials and I was
27:29told that um that were anywhere near the
27:35similar um treatment response that I
27:37would get from DBS um so there was no
27:41real thing to have as an
27:43alternative and uh i' got to the point
27:46where life was pretty difficult with
27:48three kids um I had really bad um
27:52distonic pain um which is really my
27:56worst symptom um and so when I chose to
27:59have DPS it wasn't a difficult decision
28:02for me um but I was aware that it would
28:06mean that I couldn't have any trial
28:08drugs I could obviously have you can
28:10have normal prescribed drugs along with
28:12your DBS but you can't go on any
28:14clinical trials because you it's seen as
28:16a bit of a complicated um extension to
28:20the results I think um so because they
28:24do change your program on your deep
28:26brain stimulation quite often well some
28:29people have it more often than others
28:30but um yeah to get the best out of it
28:35you need to be um Pro reprogrammed every
28:38often thank you thanks Rachel that was
28:41quite quite informative Cheney what are
28:44your thoughts on this on excluding
28:47people with DBS on clinical trials and
28:49how could this be remedied in the
28:52future yeah I think we've already sort
28:55of touched on some of the the reasons
28:58why DBS might be added an exclusion
29:01criteria at this stage so um clinical
29:04trials when a new therapy is going
29:06through clinical trials they go through
29:07a number of stages so um it's from phase
29:10one to to phase four phase one is very
29:13much about understanding the safety and
29:15tolerability of um of a new therapy and
29:18you work through the stages including
29:20more and more people and as you include
29:23more people you tend to generalize over
29:25the population more um
29:28so to begin with um and and stampd is an
29:31early phase trial um we make sure that
29:36the the inclusion and exclusion criteria
29:39are relatively strict um in order as
29:42Agnes said to get that homogeneous
29:44population um so that people are we're
29:47confident that people are um very very
29:50similar it gives us the best chance of
29:53finding a a a positive signal from that
29:57so as it we get more evidence that
30:00therapy works we can start broadening
30:02out those exclusion criteria so it may
30:05be in the future um that not that that
30:10people who have DBS may not be
30:13excluded um although I will hold my
30:15hands up and say I am not a
30:17neurosurgeon um there may be added
30:20complications of removing a DBS in order
30:23to have a cell um stem cell transplant
30:26um so factors would need to be
30:28considered but it may be possible in the
30:30future um but at this stage at this time
30:33we need to give the therapy the best
30:35chance of having a positive signal and
30:37that's why we have these tight exclusion
30:39criteria so it doesn't seem very fair
30:41now and it isn't um but the idea is the
30:46Hope is that it does broaden out um as
30:49we go along um that's that's helpful I'm
30:52going to ask ageta to chip in on this
30:54but also address a question that someone
30:56um put so might be getting a bit
30:58technical I think someone asked are you
30:59putting the cells into the to the
31:01substan so you can address that
31:05theoretically um would a DBS need to be
31:09removed to do a a cell therapy or the
31:12target sit's different in in the brain
31:15aneta yeah so uh for the first question
31:18we are not putting the cells into the
31:20substan niga which is the normal
31:22endogenous location of dopamine urines
31:24we are putting them into the putan which
31:27is the target side of the dopamine
31:29neurons this is where the dopamine is
31:31released and this is where the dopamine
31:32functions and this is in particular
31:35where there is a lack of dopamine in the
31:37parkinsonian brain um we're putting them
31:40into the pamment because it has been
31:42shown previously not from stem cells but
31:45from fetal tissue which is kind of a
31:47pre-runner to the stem cell TR that we
31:49have now where fetal dopamine nerve cell
31:53so this is a tissue donation um from
31:57aborted fetal tissue and that tissue
32:01then has been transplanted into the
32:02brains of patients in particular here in
32:05Lund in Sweden that has been done and
32:07from those studies we know that it can
32:11work to put the dopamine cells into the
32:13putan and they don't need to be in their
32:16endogenous location of the substantial
32:18 H and the advantage of putting
32:21them into the pment is that they're in
32:23the right place because the yeah this is
32:26a little Technic but the substantial
32:28 is around 10 cm away from the
32:31paman so if we were to wait for the
32:33cells I already sold you takes a while
32:35for the cells to mature and start
32:37communicating with the brain but if we
32:39were to wait for them to actually grow
32:42uh nerve processes all the way up to the
32:44pment we uh extrapolate that this would
32:47take around 5 to seven years in a human
32:50it takes around one year to do it in a
32:52rat we know that the cells can do it
32:55it's just a very slow process uh and I
32:57don't think anyone would want to wait
32:59five to s seven years for the uh
33:02treatment to work uh so we think there's
33:04a much better chance that the cells will
33:06work and we know that they can work if
33:08we put them into the putam which is the
33:10site where the dopamine is actually
33:12lacking um sorry the other question is
33:15about DBS could you imagine
33:17theoretically someone with DBS in the
33:20future also receiving the stem cell
33:22therapy uh yeah I mean I don't think
33:24there's any technical hindrance to it I
33:26mean PBS is normally in the subthalamic
33:28nucleus so it is a different site of the
33:31brain and uh it should be technically
33:34possible to go into the paman without
33:37interfering with the electrode in in the
33:39subthalamic nucleus um so I think that
33:43is possible uh but I think as Cheney
33:45just mentioned in a clinical trial
33:48setting it would be a huge confounding
33:49factor for us to include DBS uh
33:52individuals it would be very difficult
33:54for us to interpret the results from the
33:56stem cell therapy if we had DBS patients
33:59included in the trial and this is the
34:01reason um simply that that DBS is in is
34:05an exclusion criteria currently but that
34:07doesn't mean that these two therapies
34:10couldn't be combined once we've been
34:11able to assess the clinical effect of
34:14the stem cell therapy alone good that's
34:17what I hope you would say that was the
34:19right answer because I think Cheney
34:20mentioned taking out the DBS and going
34:22in but and theoretically you don't need
34:23to take any any electrodes out the need
34:27to no yeah the two locations are
34:29completely different the two anatomical
34:31locations so a lot of questions have
34:33been piling up some of them are are
34:34short so I think a lot of them are for
34:36you agneta so if I just fire through uh
34:39a few of them one first one I'm going to
34:42ask is why are under 50s
34:49yeah that's a good point
34:52um uh yeah we have actually discussed
34:56whether we should remove the uh the
34:58younger limit I mean we do have an
35:00inclusion criteria of having uh of
35:03having the diagnosis for at least 10
35:05years in advance so we are including
35:08most of the young uh patient population
35:11of course the extremely young youngly
35:13diagnosed um individuals we wouldn't be
35:16able to include and those would most
35:17likely be familial forms of of the
35:20disease some of which are atypical um
35:24but it's a it's a good point and that
35:26could be something we might you know
35:29trials that's good yeah I think
35:31definitely that will um expand um what
35:35are the risks of the transplant surgery
35:38itself uh yeah so those are very similar
35:41to the risks of a DBS surgery it's a
35:44very um the the surgery in itself is
35:47very similar to DBS uh so you uh it's a
35:50bur Hole uh in the skull and then it's
35:53the insertion of a needle and in DBS you
35:56insert an electrode instead um so those
36:00are the uh well-known uh possible risks
36:03of a neurosurgeries such as infections
36:07uh or edema or bleeding in the brain but
36:10I will say that the neurosurgeons are
36:11very good in general at avoiding that um
36:15uh they do a very meticulous planning
36:18they scan the brain in advance of every
36:21single patient to make sure that they're
36:22avoiding big blood vessels that they're
36:25avoiding penetrating uh crucial brain
36:28structures that they might damage on the
36:30way so they actually uh meticulously
36:33design the neurosurgery individually for
36:37every single patient to make sure that
36:39they're not hitting or damaging any uh
36:41crucial regions of the
36:43brain that's a a very good answer it's
36:46very controlled uh functional surgery
36:49where things a lot of things are under
36:51control um so there's a question that I
36:53think U maybe I'll ask you but might not
36:56be a you won't be able to answer but
36:57maybe you can explain the trial a bit
36:59better so someone's asked any positive
37:01feedback from The Trial that happened
37:03this year in February so I know the
37:06person is referring to you transplanted
37:08one person this February and the trial
37:10is of course a two-year trial or
37:12something but I don't know can you say
37:14anything about how it went yeah so I
37:17mean it's too early for us to release
37:20any data from The Trial we can just say
37:22that uh all we have transplanted four
37:24patients uh so far so far there haven't
37:27been any safety concerns uh but we it's
37:31too early to to say anything about
37:33functional efficacy because we have to
37:35wait for at least that one year it's the
37:37one-ear end point is the time point
37:39where we can start releasing data from
37:41The Trial uh and we still haven't dosed
37:44all the patients so in in total we will
37:46be dosing eight individuals in the trial
37:49so so far the trial is progressing uh as
37:52planned and there is a there hasn't come
37:54any major safety concerns so far and a
37:58technical question about bilateral or
38:01unilateral how are you doing both sides
38:03at the same time yes and this is
38:06actually a big advantage of the stem
38:09cells compared to the previous older
38:11trials that were done with donated fetal
38:13tissue because in those trials there was
38:16never enough tissue you were dependent
38:18on the amount of donation that you could
38:20get on every single surgery day and
38:23there was never enough tissue to donate
38:25to donate to to uh transplant the cells
38:29bilaterally that problem we don't have
38:31anymore because now we produce the cells
38:34in the lab and we can produce you know
38:36as many cells as we want and then we
38:38freeze them down in little vials and
38:41right now they're actually located in a
38:42freezer in London in the at the Royal
38:44free hospital in London and then we can
38:47ship them to the clinical sites and then
38:49we just ship the the amount of cells
38:52that's needed for for each patient and
38:54then we can go in and do everything in
38:56in one surgery and I think it so that
38:58means the surgery is a little bit longer
39:00but on the other hand it also means that
39:01the that the patient only needs to
39:03undergo one surgical session which we
39:08Advantage okay I'm going to switch to
39:10Cheney um can you maybe give some some
39:15ideas about how uh patient participation
39:18involvement could influence such a trial
39:21such as stampd or other trials um
39:23patient voice how could they design or
39:25help make these trials much much better
39:28yes absolutely so um I think most people
39:33um particularly in the UK now are quite
39:35used to um sort of the concept of public
39:38and patient involvement in research um
39:41and being asked to um get involved with
39:44the the planning and design of clinical
39:46research now we would argue that um uh
39:50that the public and patience and people
39:52with lived experience can be included at
39:53all stages of the research life cycle so
39:56that really starts from developing the
39:58research questions you know what is
40:00important to you what needs to be
40:02answered and I think in this case for
40:05for um stem cell therapy the patient
40:08voices is really important in how we
40:12design the trials to be um as uh sort of
40:16patient friendly and as acceptable as
40:18possible um so some of the work that
40:21we've done um in the past has shown that
40:24that to make the experience easier for
40:27for patients it's nothing's
40:30groundbreaking but it's small little
40:31changes in how you run and manage the
40:34trial make a big difference um you know
40:37the people that volunteer for these
40:39trials give an awful lot of themselves
40:41they're extremely um courageous um in
40:44volunteering to go for these very novel
40:47therapies um so it's really important to
40:50involve them in um designing those
40:53trials so we can make it as acceptable
40:55as possible um um making the information
40:57that we send out to people as readable
41:00and and and as useful as it can be um so
41:04that everyone knows what What's um going
41:06on it's about what we measure um it's
41:09about how we measure it patients can
41:11feed into all of that um uh patient
41:15Representatives also really really
41:17important for helping interpret um the
41:23Translating the results of Trials back
41:26out into the community and being a
41:28conduit for um for for channeling those
41:31results back out to the community and
41:33making sure that they are fed back out
41:35in a really um understandable way so
41:38they can be involved at all points um I
41:40would say yeah good fantastic Rachel do
41:43you have a comment on that I think
41:44you've been asked for your opinion on
41:48past yes I've helped um some uh
41:53pharmaceutical companies in the past
41:59um uh so I think patients should be
42:03involved or at least well yeah patients
42:06should be involved certainly looking at
42:08things like um for doctors I think the
42:11number of blood tests probably isn't
42:12that interesting um you know if they
42:15have them one weekly two weekly three
42:17weekly I don't think it matters um to
42:20some people who are writing research
42:23documents or trial documents
42:26um but I think for a patient to have to
42:29Trek weekly to a hospital or even to
42:32their GPS to have a blood test um it
42:36takes quite a lot of energy out from
42:38them it ruins their day it could be in
42:41the middle of the day so um I think it's
42:44really important like um uh Shan was
42:48saying the little things it's actually
42:50quite important to look at those um and
42:53how much it interferes with their daily
42:55life especially if they're on um you
42:58know if there was a poliy vot on I know
43:01they shouldn't know it is but but um
43:04obviously you're you're expecting people
43:06whether they're ill or not really to
43:09take um to take time out to for all
43:12these extra tests that you have so it's
43:14quite important to make sure that
43:16they're all really necessary I
43:18think I think Co actually helped that um
43:22talking to my consultant a bit about
43:24Charles he said that um
43:26since while Co was on they were able to
43:29keep an eye on patients but they were
43:30doing it a lot from video calls and
43:33going locally for their blood tests and
43:35actually they've kept that going because
43:37there's no not always a physical reason
43:40essential reason for them to come in to
43:42have their blood test taken in the
43:43hospital they could easily have it done
43:45at GPS um and so I think there's some
43:49maybe some benefits came out of
43:52covid yeah thank you thank you very much
43:55so still lot lot of questions coming in
43:57I'm not sure we can get through them
43:58well but um here's a I think a one for
44:01ageta would a patient have to stop
44:03dopamine replacement therapy I think
44:05meaning drugs um after having stem cell
44:08therapy yeah a very good question and no
44:11we don't take away uh the dopamine
44:13medication from from uh the patients of
44:16course because we know that it takes a
44:18while until the stem cells will start
44:20working so what we do is we uh let all
44:25includ Ed participants stay on the
44:27medication that they're on and then
44:30they're eval evaluated quite frequently
44:33by their neurologist to see if they need
44:34to adjust their medication and normally
44:37uh the individuals themselves are very
44:39good at saying you know if they if they
44:41think the dose is too high or too low
44:43and then uh the neurologist will adust
44:46adjust the medication as needed to
44:48handle the uh symptoms the best possible
44:51way and this is actually one of the
44:53readouts of the trial we look at what's
44:56called L Doopa equivalence um so we look
44:59at how much dopamine medication is each
45:03individual on in the beginning of the
45:05trial versus the end of the trial and if
45:07we see a decrease in the dopamine
45:10medication this is also a positive
45:12readout of the trial and of course we
45:14hope for a decrease in those patients
45:17where the stem cell therapy is is
45:19working thank you that's very clear so
45:21here's an interesting question um I
45:24believe an exercise regime is being
45:26mandated for the participants on the
45:28Kyoto trial is this going to happen for
45:30the lound Cambridge trial oh that's a
45:33very interesting uh question we are not
45:36mandating that but it's probably a good
45:38idea because quite a lot of research in
45:40animal models has actually shown that
45:43you can improve the effect of the graft
45:46if you stimulate exercise in animals and
45:50this is probably because of what we call
45:52Graft training so you basically
45:53stimulate the cells to work faster and
45:56to work better and to integrate faster
45:59into the brain that they've been put
46:01into so actually it's a good suggestion
46:04um we haven't included it now but that
46:07could be something that we could
46:09consider for future trials yeah I think
46:11on our previous webinar we covered
46:13exercise Julie Jones was involved and
46:15also Julie Jones um Adam R Parkinson's
46:18lecture was all about exercise exercise
46:20in general is very good for people with
46:21Parkin on with or without a stem cell
46:23therapy I think um so there's a
46:26interesting question about how is it
46:28determine whether gene therapy or stem
46:30cell therapy is right for you um and for
46:33that matter what is the difference
46:35between the two so let's get this basic
46:37thing out of the way what is the
46:38difference between a gene therapy and a
46:40Therapy do you want me to take that one
46:43oh yes uh you are maybe uh actually all
46:45of you have been involved so maybe I'll
46:49AGA yeah so uh gene therapy is a therapy
46:53where you put uh normally you would put
46:56a virus into the brain uh because what
46:59viruses can do is they can deliver uh
47:02genes to your cells in the brain uh so
47:06that means you're not putting in a new
47:07cell but you're kind of enhancing the
47:09function of the cells that are already
47:11there and gene therapy is in general
47:14something that's mainly investigated for
47:17genetic diseases so if you know you have
47:19a defect Gene like in cyc fibrosis or in
47:22duen muscular atrophy distrophy sorry uh
47:25it makes sense to go in and correct that
47:27Gene put in a healthy Gene and then
47:30you've kind of solved the problem it's a
47:32little bit more difficult in Parkinson's
47:34because we don't have for most cases we
47:37don't it's not a genetic disease right
47:39or we don't have a single Gene that's
47:41mutated uh but that said there are
47:44groups that are working on gene therapy
47:46and the approach here is to put in genes
47:48that can help other cells to produce
47:50dopamine so you can kind of hijack cells
47:53that don't normally produce dopamine you
47:55give them the enzymes to produce
47:57dopamine and then they start secreting
47:58dopamine uh the um potential problem
48:02with that is that you can then overload
48:04the brain with dopamine and it's
48:05difficult to control but the there are
48:07some of these in clinical trial there
48:09are also clinical trials with gdnf many
48:11of you have probably heard about that uh
48:13and gdnf is a growth factor that can
48:17promote the outgrowth and potentially
48:19the survival of the remaining dopamine
48:21neurons in the brain and there are
48:23trials ongoing with this particular in
48:25California there have also been trial
48:27trials in Cambridge uh and actually this
48:29is still ongoing there have been some
48:31failed trials but they've really improve
48:33the delivery of the vector and the
48:35expression of the dnf in the brain so
48:37it'll be interesting to see how these
48:40out thank you Rachel you've been
48:43involved in gene therapy trials I
48:48think uh yes I have but it was I have to
48:51admit it was a very long time ago um I
48:54was involved with the first Oxford
48:57biomed um gene therapy trial so it was
49:01with cancer patients not Parkinson
49:03patients who had skin lesions so
49:06obviously it was injected in and it was
49:08a lot easier to uh Monitor and a lot
49:11easier to evaluate and this was just a
49:13phase one safety study um it was taken
49:19um really seriously at the time with the
49:22idea that these viruses could replicate
49:24obviously were known not to be able to
49:27replicate because they've been basically
49:29mashed up so much that there was going
49:31to be no replication but for everybody's
49:36um for to make everybody feel better we
49:39had lots of PVE on and it was all very
49:42seriously contained um I'm not sure
49:45that's probably the case now but uh but
49:48it was very interesting at the time um
49:50it was it was um a really new thing to
49:54do um and it was fascinating because we
49:57w we injected it into breast um skin no
50:02Jews and melanoma patients who at the
50:05end of their life really had no other
50:08treatment to go for and one lady's
50:11breast lesions virtually
50:13vanished um in the time that she was on
50:15the trail so obviously something was
50:17happening um and I'm sure they've gone
50:19on now to do um further research into it
50:23yeah I think the safety of the gene
50:25trials are looking much much better than
50:27they were a decade decade ago um
50:29actually had a question that Simon
50:31answered for you Cheney um I don't know
50:33what your thoughts on this are but if
50:34one of the trials in for example Japan
50:36proves successful and we get the results
50:38from that would this speed up approval
50:41in the UK or would the current trials in
50:43the UK need to be completed first before
50:46we get approval um for UK uh you know UK
50:50use it's a great question it very much
50:53depends on the similarity ity of the
50:56product so stem cell products are being
50:59Del um developed they're all individual
51:02products and so they all need to be
51:05individually tested for safety it's very
51:08similar um to when you're looking at
51:11sort of standard drug trials so everyone
51:14might be um people might be familiar
51:16with things like satala pram as an
51:18anti-depressant there's an extremely
51:21similar molecule called
51:23esalo which is essentially the same it's
51:26just a a very very minor modification of
51:29the molecule but because it's a
51:31different molecule you do have to prove
51:34that it's safe and that it works in
51:36people before it can be licensed so
51:38certainly if the same product has been
51:40tested in another country you can go
51:43through the phases in um in a different
51:48region or a different Authority um as we
51:50talk about regulatory authorities you
51:53can go through them um quicker as long
51:55as you have the clinical information
51:58relating to that product that you can
52:01submit to the regulatory Authority in
52:04any given region um then you can
52:07accelerate the the sort of approval for
52:09that therapy coming to Market but it
52:11does depends on the identity of that
52:13that product that you're testing I'm
52:16going to also ask anetta because the
52:17sell lines I know are completely
52:19different in the two countries so what
52:20what are your thoughts on that question
52:23ageta um yeah I mean if it's two
52:25different products it doesn't help you
52:27much because each product has to be
52:29tested individually but let's say if we
52:32test stampd in Japan and maybe this
52:35person is asking about Japan because
52:37Japan has particular rules about
52:39approving stem cell therapies for Market
52:41they can actually approve a stem cell
52:43therapy to Market even before it's gone
52:45through phase three so that's different
52:47from all other countries and that does
52:49mean that you can get faster to M Market
52:51in Japan um you would still have to go
52:55through a phase three in UK or in in
52:59Europe or in in the US to get
53:02authorization in Europe and us um so but
53:06it it can potenti it would probably help
53:08your case if you have uh patient data
53:11from Japan or you have postmarket data
53:13so what we call phase three for sorry
53:15phase four data from uh Japan to support
53:18your claims of efficacy um so it might
53:22increase your chances of getting Market
53:24authorization but unfortunately you
53:26still have to go through phase three
53:28here great now we only have a few
53:30minutes left and we still have lots of
53:32questions so aeta um this is a a very
53:35relevant one as you're aware there are
53:36many symptoms of PD in your work so far
53:40um which symptoms will the stem PD
53:43product impact and which symptoms will
53:45it not yes so it's important to say that
53:49these cells are dopamine cells so
53:52they're expected to work primarily on
53:55dopamine responsive symptoms uh so this
53:58is of course mainly the the motor
54:03um other non-dopaminergic responsive um
54:07symptoms such as cognitive uh impairment
54:11for instance or let's say uh non CNS
54:15related symptoms bowel symptoms for
54:17instance we don't expect that this
54:19therapy will work on there is a
54:21discussion as to whether uh something
54:24like depression depression does also
54:26involve the dopamine system and we I
54:29know Roger Barker he he's very adamant
54:31to the idea that actually a dopamine
54:33Cell Therapy could work against Dem uh
54:35sorry depression symptoms we just don't
54:37know yet we this is something we just
54:39can't test in the animal models so we
54:41really don't know we'll have to see what
54:43the what the clinical trial data shows
54:47us great um and then uh two other
54:50questions about safety so someone's
54:52asked um will the cells can the cells be
54:56rejected if the cell's growth goes out
54:59of control how can the growth be
55:01controlled yes very good questions and
55:03actually this growth out ofc control
55:05growth is of course the one thing the
55:07main thing that uh regulatory
55:09authorities want you to show that you
55:11don't have because if you don't control
55:12your stem cells well there is a risk
55:14that they can uh grow and potentially
55:16generate a tumor in the brain so this is
55:18actually one of the things we spent most
55:20time on in the preclinical tests
55:22long-term studies in the animals to make
55:24sure that these cells don't form tumors
55:26we've transplanted more than 3,000 rats
55:29actually we've never seen a tumor so
55:30we're very confident in our case that
55:32they don't but of course we'll we have
55:34to see the clinical data on this um but
55:37this is something we really test very
55:39very rigorously before we go into
55:41clinical trial um and then the question
55:44sorry the other question
55:46was was about um rejection rejection yes
55:50so we do uh the individuals in the trial
55:52are treated with immunosuppressive
55:55uh for one year so 12 months into the
55:58tra uh and this is to avoid rejection of
56:00the transplant because it is a
56:02non-immune match transplant but because
56:05uh the brain is partially
56:06immunoprivileged so it's not a highly
56:08immunogenic site we have reason to
56:11believe that we can then retract the
56:13immunos supression after a year and that
56:14there the brain will then have a
56:16tolerance to the gra we've seen this in
56:18the fetal tissue transplants so this is
56:20different from a heart transplant for
56:22instance where you need to take immune
56:23suppression for the rest of your life
56:26yeah that's that's good news only um
56:29partial so not a lifetime of
56:31immunosuppression so last question I'm
56:33sorry again for you an this is um
56:35someone's asking about is the transplant
56:37susceptible to toxin or I guess maybe
56:41environment of toxins but also is it
56:42susceptible to getting Parkinson's
56:44disease I guess yes H and here again we
56:48learn from those old fetal tissue
56:50transplantation trials because we have
56:51brains that have been for brains where
56:53we have grafted cells have been there
56:55for a long time we actually have a brain
56:57where the grafted cells have been there
56:58for 24 years it's a very long time and
57:01from these graphs we do know that yes uh
57:04the pathology in the brain can transfer
57:07to the transplanted cells but it's a
57:10very slow process so on average what we
57:13see happens is that around 0.5% of the
57:17transplanted cells per year will acquire
57:19pathology this means that 10 years after
57:22transplantation we expect that around 5%
57:24of the cells in the graft have acquired
57:26a panonian pathology so it does happen
57:30but it's slow and we do believe that
57:33with the time frames we're looking at
57:35here that because it's so slow that the
57:37graph can still be functional for the
57:42patient great um fantastic I think
57:46that's all the time we have um for for
57:50questions um I'm G to yeah okay I'm just
57:54going to SU up what what I learned I
57:55learned a few new things that was was
57:57fantastic so um the first thing that
57:59agesa told us is that um the stem cells
58:02that we talk about are talking about in
58:04this seminar are Pur potent so I
58:06actually describ that these are very
58:07primitive cells that can be turned into
58:09anything anything in the body any type
58:11of cell so agneta and others are turning
58:14them into dopamine producing cells to
58:17replace the dopamine neurons that are
58:19lost in Parkinson using a physical
58:21transplantation so they physically put
58:23new cells to replace the cells that are
58:25lost and they put them into the paman
58:27not into the substantial but the
58:29paman is the area where dopamine is
58:31needed and one thing I learned is that
58:34the good news is that although DBS
58:36people with DBS are excluded at the
58:38moment but the theoretical possibility
58:40of having a stem cell transplantation
58:42also and having DBS simultaneously is
58:45not theoretically impossible the sites
58:48of transplantation and placing of the
58:50electrodes are completely different
58:51anatomical sites the paman versus the uh
58:54subthalamic nucleus so um it's it's
58:57great to hear that people like Cheney
58:59are really um trying to measure or
59:02trying to gather the patient experience
59:04getting the clinical trial designed to
59:06include the voice of people with
59:08Parkinson as much as possible um and the
59:11inclusion exclusion criteria we heard
59:14are quite strict so someone mentioned
59:1676 they meet all the criteria but
59:19they're 76 right now so on paper they
59:21would be excluded but he probably is a
59:23very you know fit person that would be
59:25perfect for this trial so 50 is 520 to
59:29be the lower limit should this be should
59:30this be reduced um the answer I think is
59:33clearly yes these criteria need to
59:35expand and they will expand I think as
59:37we move forward we'll see expansion of
59:39these criteria as we had uh from DBS
59:41someone asked about DBS earlier the
59:43inclusion criteria was probably quite
59:45small but then expanded quite a lot and
59:47I really appreciate all the uh comments
59:50from Rachel so Rachel who's been living
59:52with Parkinson's for about eight years
59:54has had BBS has some participation and
59:57and Advising on clinical trials I think
59:59her comments were were absolutely
01:00:00Splendid so I thank I thank you also ve
01:00:03very much for joining joining joining
01:00:05the meeting and that I think that's us
01:00:08um thank you very much and we'll see you
01:00:10uh at the next webinar in about three
01:00:12months time thank
