How patients have helped us with our research - University College ...

46 UCLH BIOMEDICAL RESEARCH UNIT
Joining forces to pioneer gene therapy
A unique partnership between
patients, a charity and UCL
researchers is helping doctors
look for a way of ending the
misery of haemophilia B.
Haemophilia is a clotting
disorder which causes
unpredictable and spontaneous
internal bleeding. A person with
haemophilia B has a genetic
defect and their liver is unable
to manufacture a protein called
‘factor 9’. Factor 9 is essential
for clotting.
Excitingly, a team from the
Haematology Department at
the UCL Cancer Institute has
been pioneering a technique
to correct the genetic defect.
But clinical researchers could
not have got this far without
funding from a charity,
volunteers and extensive patient
consultation.
Patients say what
they want
To correct the genetic defect,
a normal copy of the factor
9 gene needs to be delivered
safely to the liver of the patient
with haemophilia B. It took the
UCL team 10 years to develop
a suitable vehicle – known as a
vector – for carrying the genetic
material.
Researchers could
not have got this far
without patient input
But they couldn’t have done
this without funding from
organisations like the Katharine
Dormandy Trust. With gene
therapy the next big thing
in haemophilia research, the
charity funded the original work
that enabled the trial to start.
Patient feedback was then
crucial in helping researchers
develop the gene therapy.
“Initially we were going to
inject the vector into the blood
vessels serving the liver, but
this required a small operation,
and patients told us they didn’t
want that. They already treat
themselves by injecting factor
9 into a peripheral vein, so
we used that route instead,”
says lead researcher, Dr Amit
Nathwani, who is from UCL and
works at the haemophilia and
haemostasis unit at the Royal
Free Hampstead NHS Trust.
Similarly the vehicle initially
used by researchers was a
harmless adeno associated virus
(AAV) that is so common most
people are immune to it and
the body’s immune defences
would normally attack it. To
avoid this, there were two
options: either use suppressant
drugs or modify the vector.
Patients didn’t want to take
the drugs, so the AAV type was
changed to a less common one
and its DNA altered.
Other hurdles
But even with the biological
hurdles overcome, it was a
challenge to get a trial off the
ground. Previous problems
with haemophilia treatment,
including HIV-contaminated
blood products, meant patients
and doctors were wary of new
treatments.
The Katharine Dormandy Trust
played a key role by running
focus groups for doctors to
explain the trial’s objectives and