HD research: 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.
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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