Download Vaccine trial shows early promise

research focus
research focus
The clinical trials for
MonoPepT1De are
open to anyone aged
between 18 and 40 in
the 100 days since being
diagnosed with type 1
Vaccine trial
shows early
promise
Mark Peak man with his lab group
Our volunteer writer
Nikhil Patel finds
out the latest on the
research at King’s
College London which
is testing a vaccine with
the potential to at least
slow down beta cell
destruction
Know your
facts on
autoimmunity
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A
type 1 diabetes vaccine, with
the potential to be ‘absolutely
brilliant’ according to a patient
who has taken part in its trial, is
becoming a real possibility.
In fact two clinical trials at King’s
College London are seeking to
develop a vaccine that could slow
or halt the process that destroys
insulin-making cells.
These innovative trials are being
pioneered by Professor Mark
Peakman who, during his many years
of type 1 autoimmunity research, hit
upon the idea that it was possible
to reverse the damaging immune
system response by creating a
‘protective’ immune response.
His collaboration with other
experts, particularly Professor Colin
Dayan of Cardiff University, turned
this initial hypothesis into two trials,
MonoPepT1De and MultiPepT1De,
that will assess whether a recently
diagnosed person’s ability to make
insulin can be preserved.
Thanks to JDRF supporters, the
charity has been able to fund these
trials, which use tiny fragments of
a precursor to insulin, known as
‘proinsulin’, to teach the immune
system to allow insulin-producing
cells to flourish.
This is very similar in concept to
recent work on treating allergy that
uses peanut extracts to teach the
body to tolerate peanuts.
The clinical trials are open to
anyone aged between 18 and 40
who have been recently diagnosed
with type 1.
Taking part involves receiving small
injections and being monitored
regularly over a 6-12 month period.
Alex Collins, 34, is an investor from
London who recently took part in
Autoimmune conditions affect around four million people in the UK.
the MonoPepT1De trial. He was
diagnosed in August 2013 and
signed up to take part in the trial
a couple of months later. He said:
‘It’s impossible to say whether my
condition has improved directly
because of the vaccine, but since
I got my blood glucose under
control after diagnosis my HbA1c
has been between 5.7 and 5.9.
‘In other words my levels are
very good, which may be partly
because of the trial.’
‘[The vaccine] would be absolutely
brilliant for anyone newly
diagnosed. If doctors can halt or
even slow down the progress of
type 1 once it’s been diagnosed it
would have a huge impact on the
quality of life of those suffering
from the condition.’
Alex, a dedicated JDRF
supporter who has run the
London Marathon to raise funds
for research, added: ‘I cannot
recommend the clinical trial
highly enough.
‘Having a lot of contact with
diabetes professionals is
fantastic. I’m impressed with the
care I get from the NHS and I get
on well with my doctor, although
I only see him for half an hour
every six months. Particularly
when you’re newly diagnosed it is
amazing to spend more time with
diabetes professionals – for that
reason alone it is worth doing.’
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Volunteer Editor-in-Chief
When protection is the
best means of attack
Mark Peakman, Professor of Clinical Immunology
at King’s College London, talks to Jonathan
Henderson, editor-in-chief of Type 1 Discovery,
about the MonoPepT1De and MultiPepT1De trials.
This is the latest step in pioneering research into
developing a vaccine
J
onathan Henderson: You say
you are taking ‘a vaccine-type
approach’ to slowing or preventing
the type 1 process. What does this
mean?
Mark Peakman: The concept of a
vaccine is that you stimulate the
immune system in a safe encounter
that protects the host from whatever
the threat is. Usually you’re doing
this against a virus and so you
present the immune system with bits
from the virus in a harmless way. The
aim then is to develop a response
that protects against an encounter
with that virus in the future. In type 1
diabetes we believe that the immune
system identifies the insulinproducing parts of the body as a
threat. So we’re aiming to present
these elements to the immune
system in a safe way that promotes
a protective response rather than an
aggressive one.
JH: And this is what these
trials are investigating?
How do MonoPepT1De and
MultiPepT1De differ?
MP: MonoPepT1De was a
prototype that allowed us to get
into human trials, show safety and
test biomarkers and tolerability.
MultiPepT1De is the second
generation that will be ready to go
into trials for the first time in 2015.
MonoPepT1De was a single fragment
from the beta cell that we were
using as a drug and MultiPepT1De is
multiple fragments from the beta cell.
So we believe it should have greater
breadth and be more powerful.
Many people with type 1 live with at least one other autoimmune
disorder. Around eight per cent have coeliac disease too.
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research focus
research focus
There’s another dimension to
JDRF, which is that they bring you
into the right room. When we’ve
needed to speak to other people
or institutions, JDRF has been
incredibly helpful
Your
support
has helped us to make
this research possible.
To fund more research
like this, visit
jdrf.org.uk/donate
JH: A few years ago we
interviewed you about a JDRFfunded study you were running
called DGAP (Diabetes Genes,
Autoimmunity and Prevention
Project). Does this fit with the
work you’re currently doing?
ts
Helper T cells responding to isle
Some cells have a good response (green),
others a bad one (red). The cells that produce
both responses (yellow) are particularly
interesting to Prof Peakman’s team.
The concept of
a vaccine is that
you stimulate the
immune system in
a safe encounter
that protects the
host from whatever
the threat is
Know your
facts on
autoimmunity
16
JH: These trials are focusing on
adults newly diagnosed with
type 1 diabetes. Does this work
have any relevance for people
who have had type 1 for many
years or for children?
MP: First, it is worth saying that
there is some research just coming
out that suggests for the first time
that there might be benefits for
people who have had type 1 diabetes
for much longer than three months –
even up to a few years. But in answer
to your question, yes, we are hoping
to launch studies in younger patients
with type 1 and some small pilot
studies in individuals who don’t have
diabetes yet but who we know are at
risk. This is definitely on our radar at
the moment.
JH: If treatments such as
MultiPepT1De can work to
prevent type 1, how would you
get it to the right people at the
right time?
MP: What all the animal studies
have suggested is that the earlier
you can get this kind of treatment to
patients the better. So if the trials
show promise we’re probably talking
about robust screening programs of
high-risk individuals. These might
be individuals who have a family
history, but one might even consider
screening the school-age population.
And this is not such a ridiculous
suggestion as it may sound. It is a
model that is actually being developed
in Bavaria, Germany, at the moment.
So this is how we might get to the
high-risk groups as early as possible.
There are thought to be more than 80 autoimmune conditions,
each affecting a different part of the body.
MP: Yes, because we showed
in DGAP that there are probably
different types of immune responses
in patients with type 1. These
different types of responses may
require different kinds of therapeutic
approach, which we’re beginning
to call personalised medicine: the
right drug for the right patient at the
right time. Based on the work we did
in DGAP we think that the vaccines
may be even more effective in some
people than in others.
JH: Has JDRF played a
significant role in your type 1
research?
MP: Yes it has in many different
ways. For example, JDRF funded
the basic DGAP studies and the
MonoPepT1De clinical study. But
there’s another dimension to JDRF
that people are probably less aware
of, which is that they bring you
into the right room. They get you
talking to the right people. This has
been very important in taking our
development forward. When we’ve
needed to speak to other people
or institutions, whether it be other
funders, pharmaceutical companies
or regulators, JDRF has been
incredibly helpful.
JH: Other than funds, what
would help speed the progress
of your research?
MP: Being able to get trials up and
running and enrolled quickly. It is one
of the things that keeps me awake
at night: are we going to be able to
deliver the number of patients we
need, in the time when we have
the funding? Because when you’ve
got a study open and you’re not
recruiting you’re basically burning
cash. So getting patients enrolled
and engaged and getting them to
stay in the studies is tremendously
important.
Biography
Mark Peakman trained
in medicine at University
College London and
pursued postgraduate
training in clinical
immunology. After
he received his PhD
based on studies of
the immune system in
type 1 diabetes, he held
senior positions at the
University of Pittsburgh
before returning to the
UK, and he now oversees
a research group at
King’s College London
in the Department of
Immunobiology.
If you’d like to get involved in a clinical trial, which is a vital
step in making this vaccine a reality, visit jdrf.org.uk/trials.
You can take part if you’re aged between 18 and 40 years and have recently been diagnosed with type 1 diabetes.
Many autoimmune conditions share similar underlying mechanisms – this
means that drugs developed to treat one condition, such as psoriasis, may be
effective in other conditions, such as rheumatoid arthritis.
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