CURRENT TREATMENTS

Current therapies are aimed at managing the symptoms of HD. Whilst a number of pharmaceutical therapies exist to alleviate motor and psychiatric symptoms, there are no pharmacological approaches to delay the rate of cognitive decline seen in HD. Psychiatric disturbance including depression and irritability can be assisted using standard antidepressant drugs along with mood stabilizers (e.g. carbamazepine, risperidone, olanzapine, clozapine, quetiapine). Alternatives such as tricyclic antidepressants can help manage the depression, but patients with HD typically show better tolerability of selective serotonin reuptake inhibitors (SSRIs). For motor symptoms, chorea may be partially relieved by a small number of treatments but at the cost of side effects, e.g. tetrabenazine, which has been reported to have a beneficial effect may also exacerbate parkinsonian symptoms, produce sedation and hypotension and related to profound depression in a proportion of individuals. Antipsychotic medications such as sulpiride and haloperidol may be used, although again the anti-parkinsonian and sedative side effects may be troublesome, and some authorities favour drugs such as olanzapine.

FUTURE TREATMENTS

There has been much progress in working towards finding an effective treatment for Huntington’s disease. For up-to-date news on the progress of potential new therapies please visit: www.set-hd.net

To summarise:

Neuroprotective studies
Neuroprotective studies are currently taking place in both preclinical (animal) and clinical trials. Some of the compounds may have the potential to be effective in delaying the course of the disease, but require larger scale and longer studies so that any true neuroprotective effects can be determined. Further review and discussion of promising neuroprotective compounds are underway within the Neuroprotective Treatment Working Group within the HD Network.

Neural transplantation
For Huntington's disease, there is evidence from animal studies that cells from fetal brain tissue can be transplanted into animal models of Huntington’s disease and can partially restore some of the neural circuits damaged by the disease. Fetal tissue is not the same as stem cells but it is a step in working towards stem cell therapies.

Taking results from animal studies to the clinic is a long and complicated process and is crucial to determine whether the treatment can be effective in people. Human tissue (collected with full ethical permission and consent from the maternal donor) takes a long time to grow and connect with the individual’s brain, and so such a therapy in people should be properly evaluated 2-4 years after the initial implantation. Currently, there are two ongoing systematic trials looking at the efficacy of fetal brain cells as a therapy for Huntington’s disease. One trial is coordinated here in Cardiff (as a collaboration between centres in Belfast, Cambridge, London Hammersmith Manchester,), and the other trial is taking place in Creteil, France.

The UK trial has reported that the procedure is safe (Rosser, A. E et al. (2002). J. Neurol. Neurosurg, Psychiatr, 73, 678-85). However, at this early stage in this trial, it is not yet possible to determine the clinical benefits. Meanwhile the French group has reported both safety and preliminary evidence of efficacy of the procedure in 5 patients (Bachoud-Levi, A. C. et al. (2000) Lancet, 356, 1975–1979; Bachoud-Levi, A.C et al. (2006) Lancet, 5, 303-9). Three out of the five have shown selective improvements or stability in certain aspects of their lives (e.g. quality of life, mobility, and aspects of cognition). However, not all those involved in the trial had positive results and a further study is now underway to try to establish efficacy with more certainty in a larger group of patients and also to try to understand the factors important in producing a successful transplant.

However, one limitation of this approach is the rarity of being able to collect enough tissue for all those who would need or request this therapy. Thus it will be important to identify an alternative source of donor cells.  Stem cells may eventually provide such a source as they can be caused to proliferate in the laboratory.  The effectiveness of this cell source is still uncertain and work is still at the laboratory phase and will need to be rigorously evaluated before reaching clinical trials. That said, since we know that the protocols used for implanting fetal tissue are essentially safe, this has paved the way to make it quicker to implement studies with stem cells as and when this becomes possible.

Gene therapy
RNA interference (i.e. preventing the faulty gene from working) is conceptually one way in which the effect of the mutation might be halted or prevented. Progress into this concept is relatively new and has so far been restricted to cellular models of the disease. One of the major problems for researchers at the moment is being able to transfer the methods used in molecular/preclinical research into clinical trials: existing techniques harbour many methodological difficulties which need to be overcome in the preclinical research before clinical trials can be initiated.

Clinical trials
Until recently, controlled clinical trials in Huntington’s disease have been limited by insufficient participant numbers and scientific merit. With the advent of national and international collaborative groups (e.g. HSG, European HD Network, NECTAR), it is now possible to conduct systematic research into the safety and effectiveness of possible therapies for Huntington’s disease. We are confident that such networks will facilitate progress towards developing safe and effective treatments for preventing, delaying and possibly halting the disease.