2007 World Congress on Huntington's Disease

European Huntington’s Disease Network and World Congress Meeting Feedback

Dresden 2007

This combined meeting of the European Huntington’s Disease Network, and the World Congress on Huntington’s Disease was held in the lovely city of Dresden in September. It provided an interesting insight into some of the excellent research that is happening throughout the world. I have attempted to summarise the main focus of the five days – not an easy task!

Nancy Wexler talked about the ongoing Venezuelan project. This is a prospective study that has been ongoing since 1979 and involves/has involved 18,149 participants. One of the striking things about this presentation was that because there is such a large incidence of HD in this population having HD is actually the normality rather than the exception.

What the future holds – A geneticist’s perspective.

This presentation looked at the fact much current research focuses on looking towards a treatment for someone who is already symptomatic but actually perhaps we need to focus on looking at what happens before this point. It was suggested that research goals should be looking at prevention of the disease and delaying the onset of symptoms in people who are not yet symptomatic. In addition to this there is a need to looking for treatments for people who are symptomatic that can halt the progression of the illness, delay or reverse symptoms and treat symptoms. It was suggested that genetic criteria may trigger pathogenesis and therefore it was important to study genetic modifiers. It was pointed out that there are some real strengths in HD research such as the existence of networks such as the Huntington’s Study Group and European Huntington’s Disease Network, there are many keen experts and researchers, the patients are willing and enthusiastic about being involved in research, there is the ability to focus on earliest abnormality and there is a single goal.

Some suggested weaknesses include: most of the focus to date has been on looking at the later stages of the damage to cells; there is incomplete knowledge about the protein huntingtin causes some cells in the brain to be damaged: there are obvious problems around trialling drugs on people who are known to be gene carriers, but are not yet symptomatic, therefore effectively well, when there is little known about how the drugs may affect them, particularly when there is a bias about risk taking in the current environment. We also know very little about the impact of other genes in relation to the onset and progression of HD.

Basic mechanisms of HD – we know that the protein huntingtin has a neuroprotective role, is present in all cells and is needed to exist. It is thought that when this protein is abnormal it may be responsible for proteolytic cleavage and the development of the aggregates that form. It is known that as the disease progresses abnormal huntingtin is increased in the nucleus of the cell. It is also known that neuronal dysfunction precedes neuronal loss so this provides an opportunity to target treatments before the loss occurs. It is still not known if the aggregates damage the cell or alternatively are a mechanism for the cell protecting itself from harmful effect.

RNA Therapeutics – A cure for HD or a dream without a future? Huntingtin is expressed in all tissues and expressed throughout development. DNA is copied into RNA which is then converted into a protein. RNA acts as a “messenger” so one of the possible ways to prevent the development of HD is to block the messenger. The advantage of this is that it offers the potential for disease prevention. However the disadvantages include the problem of what happens if the production of the normal gene is reduced; it is not known what impact it would have on other genes, and it is not known how much would result in toxicity. Some of the challenges to be overcome in looking at this treatment are the need to be able to target the brain, it is not known how much of the brain is needed to be reached, how well the delivery systems would be tolerated, can we survive without normal huntingtin, is it possible to target the mutated huntingtin, it is not known how little huntingtin is needed or how safe the treatment is likely to be.

Understanding changes in the brain – The normal and abnormal protein are found in all cell but an area of the brain called the striatum is particularly sensitive to abnormal huntingtin. Actually this area of the brain has several names which can cause confusion. (You may hear it called the basal ganglia or sometimes the caudate and putamen nuclei) By the time a diagnosis of HD is made more than 50% of the striatum in the brain has already been destroyed this damage begins years before diagnosis. This is not the only area of the brain to be affected, thinning of the cortex of the brain occurs in early HD.

CHDI – this is a not for profit biotech company that is funded entirely by donations. The aim is to rapidly discover and develop drugs that will prevent or slow down HD, and looks exclusively at potential treatments for HD.

Recent and up-coming HD trials – the Huntington’s Study Group (HSG) and European Huntington’s Disease Network (EHDN) are working together on clinical trials. They are currently running two observational trials those being the registry project and COHORT. There is also PHAROS which is looking at people who are at risk of HD but do not know their status, and PREDICT which is looking at people who are known to have a positive predictive test but have not started with symptoms. The HSG have undertaken/ are undertaking 4 clinical trials, those being Ethyl-EPA, Dimebon, which is an antihistamine, minocycline and Co- Q10. in addition there are plans for three additional trials for creatine, ACR – 16 and Co-Q10 for people who are not yet symptomatic.

Biomarkers for HD – HD lasts for a long time so we need to be able to measure the effects of any treatment. Those of you have participated in research will know that a lot of different rating scales are used. Although these rating scales are the best we have they are difficult to administer. A biomarker is a change which can be measured in say, blood, urine or on a brain scan which changes with onset of the HD and during the course of the illness. If suitable biomarkers could be found this would make assessment of future treatment much easier. Overt signs of the disease can often be seen by families or the person with HD for up to 2 years before a diagnosis is made. Ideally a biomarker can be found that would enable the introduction of any possible therapies by early detection of the illness or even presymptomatic changes. Biomarker research has led to an increased understanding of HD.

Standards of Care – there is no evidence base for good practice in HD, there is a need to use experience to audit and provide guidelines for the future. Any guidelines need to acknowledge HD as a family illness. Weight loss in HD – there is evidence to suggest that early inthe illness there is an increased energy metabolism. Weight loss frequently occurs as part of the disease process. We feel that treating weight loss is a good thing but curiously enough there are not many studies on this basic aspect of care. Emotional recognition – people with HD have difficulty recognising emotions in other people. It is sometimes described as being less perceptive of other people’s needs. This could be described as an HD blindfold. This particularly applies to those negative emotions such as fear, anxiety, and disgust and is not limited to facial expression so includes vocal recognition as well. This is evident early in the illness, and may be present even before diagnosis. This provides implications for clinical practice and social situations. If carers understand this it may be easier for them to look after someone. Juvenile Huntington’s disease (JHD) – A European Huntington’s Disease working party gave an update – this is an international collaboration has resulted in a natural history study and an extension of a study of the needs of carers which was started by the HDA here. There has been a summary of current knowledge and publications. There is a project looking at current treatments used in JHD and also looking to develop standards of care in this area.

Cath Stanley
Head of Care Services
Huntington’s Disease Association