Stem Cell Research & Aniridia – Sajjad Ahmed – Cornea Connect 2019


[Sajjad] All patients with any stem cell loss
were put into two groups – the two groups that I’ve discussed with stem cells
and without stem cells. And everyone was randomised, which meant that
no-one knew which arm you were going into of the trial. And most of the
patients with aniridia went into the trial arm, so they got stem cells, and
most of the treatment. Most of the patients that had chemical burns went
into the control arm. And it just happened that randomisation resulted in
that. What that trial showed was that in patients that have aniridia, and have the
stem cell problems, by replacing the stem cells it does have some impact. However
what we do know from other trials that have been done before, that over time,
and certainly by three to five years, the stem cells that have been put on the eye
from the surgery tend to disappear again, or they stop functioning again. And that
leads us on to the new trial that Julie’s hopefully going to be discussing
with you in the next few talks. What we think happens in aniridia is that you
can’t just replace the stem cells, because the environment that the stem
cells have are going or staying, that’s abnormal as well. And historically we
haven’t really replaced that. So what we plan to do is we plan to replace not
only the stem cells by surgery, but also the environment that the
cells are in as well. So by replacing everything we hope that the
outcomes will be much better. And that’s a trial that’s been funded by the
Medical Research Council. We’re hoping to start recruiting into the trial next year,
probably middle to third quarter of next year. The other thing that we’re looking at
particularly is… so that’s a surgical treatment, and that’s what we
can potentially offer and may well significantly help the cornea in patients
without the stem-cell loss in aniridia. We won’t know the outcomes for
that for at least another five years beyond initiation of the trial. But we
were also interested in knowing what we can do earlier on. So in the first and
second decades of life. And we just started a project with one of our
research fellows, where we look after about 123 patients who have aniridia,
but have the corneal changes with it. So that’s probably one of the largest
groups of patients in the world. And what we’re wanting to do is
we’ve gone back and looked at what outcomes have happened from interventions
that we’ve made, such as corneal transplants or cataract surgery. But
we’re also particularly keen on looking back at the mutations that everyone has.
So a large proportion of patients who have aniridia will have mutation screen,
and they’ll have a blood sample taken away. And hopefully you will also have had
a sample taken. And we go and look to see what the mutation is.
And why we’re interested in that is we think that if you look at aniridia as a
whole, not everyone gets the corneal changes, but some subgroup of
patients do get it, and get it very badly. We’re interested in knowing what
mutations particularly make you prone to that. And the reason for doing that is
that we can then, when we have a child in front of us who has aniridia,
we’re able to then take their blood, do a mutation screen, and then we’re then able
to determine whether or not they’re at a high risk of getting corneal problems.
And if they are we can then do much more frequent monitoring in their first and
second decades of life. And there are certain things that we can potentially
do that might delay the progression of the disease. For example, serum drops
is one potential treatment which we don’t often do early on. The
other thing that we’re wanting to look at is what particularly happens in those
mutations, what other genes interact with that mutation, and then
what the outcome is, and whether or not we can block those in
some way. So that’s really hopefully gonna give you an idea of what we’re
currently doing with our aniridia research program. And there’s obviously
a lot of work that’s still going on in the lab. But we’re hoping, with the
interactions that I have with Julie and her team, we’re hoping to take
a lot of those things into clinic much more effectively. I think
that’s probably about it. Alex? [Alex] Yeah, thank you Saj. If anyone has
any burning questions now for Saj, please feel free to raise your hand. [James] You said about the environment for
the stem cells. What do you mean by that? [Sajjad] So there’s two.
What we call stem cell deficiency is a disease which happens
from various causes, including aniridia. What happens is the white part
of the eye, the conjunctiva and its blood vessels come on to the
cornea. And that happens for two main reasons. Either you’ve got a true loss of
stem cells. So for example if you’ve got a chemical burn, you tend to lose the
number of stem cells. But there are many, many diseases such as the inflammatory
diseases, and the genetic diseases like aniridia, where it’s not just the fact
that the stem cells are not normal in number. There might well be a normal
number of cells, but they’re not able to grow and proliferate on the eye.
So they’re not able to multiply on the eye to produce daughter cells. And
what that then means is that if you normalise the environment, it could well
be that the stem cells that are present there start functioning normally again.
So stem cell deficiency has historically been seen as just a loss
of stem cells. But now we’re starting to realise that actually that’s
not the whole story. You need to have the right number of stem cells but
you need to have the right environment, the right blood supply, the right growth
factors in the environment, the right what we call the matrix, so where the
stem cells sit, that has to be normal. [James] So that would be what you’d add,
as it were. How would that work? [Sajjad] Whereas before we’ve just
transplanted stem cells, in the hope that that will increase the numbers, we will
now attempt to transplant the stem cells with their own environment in place as
well, so we normalise the environment. Does that answer your question?
[James] Mmhmm. [Alex] Thank you.

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