HD research news - medical research into treatment & prevention
Neural transplantation
in Huntington's disease
Summary
of Conference Presentation by Roger Barker
October
2000
Huntington’s disease
is an incurable neurodegenerative condition that has as part of its
core pathology a loss of nerve cells deep within the brain in a structure
termed the striatum. This structure receives and makes connections to
other areas of the brain, especially the cortex and it is unclear whether
the progressive pathology of Huntington’s disease can all be attributed
to the loss of striatal neurons or whether the pathogenic process involves
cortical as well as striatal neurons. Nevertheless we have embarked
on an MRC supported clinical trial that tries to repair the striatal
damage in Huntington’s disease through the implantation of developing
fetal striatal tissue into the degenerating striatum of patients with
mild disease.
The
experimental rationale for this comes from a number of sources, although
to date the model that has been used to study this is one in which the
striatum is lesioned with a chemical that is toxic to nerve cells (quinolinic
acid). This lesion produces behavioural deficits in the animal that
can be monitored, and fetal striatal tissue not only survives being
implanted into the lesioned striatum but makes connections to and from
the host brain and reverses many of the behavioural deficits exhibited
by the animal. This has now been shown not only in rodent models of
Huntington’s disease but in non-human primates.
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This led to the development
of a clinical transplant programme for Huntington’s disease in
Cambridge, that has recruited patients with mild disease from a number
of centres as part of the UK consortium working on this reparative approach
(NEST-UK). The patients in all centres are studied longitudinally using
a number of tests, but mainly involving assessment with the United Huntington’s
Disease Rating Scale (UHDRS). This is combined with a protocol for imaging
the brain either structurally using MRI or functionally using positron
emission tomography (PET). This latter scanning technique allows for
the visualisation of chemicals and the proteins they interact with in
the living brain and thus will enable us to know whether the grafted
tissue is expressing the right markers of striatal tissue. This latter
tissue is obtained from aborted fetal tissue and the use of it in this
transplant programme has required discussion at national and local level
with a number of ethical bodies. This tissue has now become available
and so the transplant programme which was conceived in 1995 with the
recruitment of the first patients has now commenced.
The transplant trial involves
two phases, phase 1 is a safety study with efficacy as a secondary aim
and in this patients receive grafts on one side of the brain only. If
the procedure is shown to be safe, then phase 2 will involve grafting
the other side of the brain in these first patients followed by grafts
on both sides of the brain in another small group of patients. It is
then anticipated that any benefit from the grafts will not be apparent
until at least 12 months after transplantation.
- HDA contributes
to this research
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