World Congress Manchester report Sept. 2005

Manchester Pictures

Development Officer Report 2005

World Congress Toronto report August 2003

28 YEARS INTERNATIONAL INVOLVEMENT

20 YEARS INTERNATIONAL DEVELOPMENT

The first HD society in the world, the Committee to Combat Huntington’s Disease has been established in 1967 by Marjorie Guthrie, whose husband died with HD in the same year. Marjorie said at that moment: “I will devote my life in finding answers”. The first newsletter ever has been published in spring 1968.

Before I became involved in HD, in August 1974 the first meeting with Marjorie Guthrie (USA), Ralph Walker (Canada) and Mauveen Hart (Jones) took place in Washington.

The Research Group on Huntington Disease of the World Federation of Neurology has been established in 1967 by the Canadian doctor André Barbeau in Montreal.

In 1977, just one year after the founding of the Dutch HD Society, the 7th Workshop on Huntington’s Chorea of the Research Group on Huntington’s Chorea of the World Federation of Neurology was to be held in Leiden, The Netherlands.
We, board members of the Dutch HD Society thought: why not trying to organize a parallel meeting with the HD societies all over the world. So we did and the next countries were present: Australia, Belgium, Canada, France, Netherlands, UK and USA. These were all the existing HD lay Societies worldwide. Next to these there was also a HD Society in West Germany, but lead by professionals.
We were allowed to listen about half an hour to the scientist! Things can change!!!!

In 1979 both meetings took place in Oxford (UK). New countries present were Germany and New Zealand. Here the IHA was formally established with Marjorie Guthrie as president and Gerrit Dommerholt as secretary.

In 1981 the meetings were in Leuven (Belgium) with Italy as new country.

The 1983 meeting was in Niagara Falls (Canada), just after the death of Marjorie Guthrie.

The 1985 meeting was in Lille (France). New countries: Denmark, Ireland and Norway. Ralph Walker became president and I vice-president. This year my work as development officer started.

I was in a different position comparing with Marjorie. She was well known and accepted by the scientists. I was mister nobody. I started with letters to different Ministries of Health. Israel reacted and contacted me to Nira Dangoor. The first success was there: the Israeli Support Group for HD Families.

The next year one of the Israeli members was married with a woman from Sweden. She read in a Swedish newspaper an advertisement of the Swedish HD Society in establishment, so I was able to contact Patrick Strand and his sister to support them in the establishment.

In 1987 the 7th IHA meeting was in Santa Margherita Ligure (Italy) with new countries: Israel, Sweden and South Africa. I got to know a lady doctor from Spain ( Maria Ramos) and tried to interest her in the founding of a Spanish HD Society, which turned out that Spain attend the 1989 meeting in Vancouver (Canada). Also new countries were: India and Switzerland.
In Vancouver I became president of the IHA.

In 1988, I got in contact with a neurologist in East Berlin (DDR = German Democratic Republic). Unfortunately he went to Canada, but the HD families became the support of the German HD Society after the fall of the Berlin wall.

Late 1989 after the “soft” revolution in the communist countries, the German HD Society organized a couple of weeks later the first HD meeting in Berlin for west and east Germany. I was invited to attend this meeting.

By the way, I attended several family meetings in Germany in the years before. As I am a slow starter, I hated the gymnastics early in the morning.

1990 was a remarkable year because I was pensioned from the armed forces and got more time to travel and was allowed to travel in the former communist countries. A German doctor invited me to travel to Linz (Austria) for a HD family meeting. It was my first attempt to try to establish a HD society by motivating people personally. With help of the Stockinger family we succeeded!

In 1991 after a family meeting in Linz (Austria) I had an appointment with Jana Zidovska in Dolni Brezany near Prague (Czechoslovakia). For years a contact with an older lady doctor existed, but she thought that she was to old to try to establish a HD Society and asked Jana to meet me, which she did. Streets in her village did not have a name; the houses had only a number, but she told me I’m living opposite a super market. I have been driving many times in the village but could not find a super market. I did not realize that a super market in her country looks different compared with super markets in my country.
Jana organized a symposium for her colleagues at the university. She told me that mainly about ten people would attend such meetings, but when we entered the room it was overcrowded. People were even standing on the balcony. Jana and I were talking to these people, it was just great. Afterwards we had the first meeting with HD families and the founding was there!

The 9th IHA meeting in 1991 was in Cardiff (Wales) with new countries: Czechoslovakia, Scotland and Austria.

I think it was in 1992 that I was invited by the Irish HD Society to attend a family meeting in Dublin. Also a delegation HD family members from Northern Ireland were present. A doctor and I were introduced to the president of Ireland: Mary Robinson. I was allowed to talk to her about predictive testing, which was not allowed at that time in Ireland and the need to accept HD as an incurable disease, which would have financial profits. Indirect, this meeting lead to the establishment of a HD society in Northern Ireland and to the possibility for testing outside Ireland with counseling inside Ireland. Bernie and I had two radio interviews in that week.

The 10th IHA meeting was in Boston (USA) in 1993 with the new countries: Northern Ireland, Mexico, Russia, Ecuador and Indonesia. For some time I was in contact with doctors In Ecuador, Russia and Indonesia. Unfortunately this has not lead to the establishment of HD societies in Ecuador and Indonesia.

Due to the separation of Czech Republic and Slovakia I had to try to establish a HD Society in Slovakia. Via the Canadian HD Society I was in contact with a HD patient in Slovakia. He was willing to introduce me to a geneticist in Banska Bystrica. At that time the IHA did not have much money to support my development work, so I stayed always with a family. When we had contact and made an appointment to visit him, I asked him to look for a very cheap hotel. You can stay with my family he said. OK, no problem for me. It was a hell of a job to find his house. The only thing I had was the name of his village and the house number. It took a lot of time before I found somebody who was able to speak English or German. The man, who I found, knew that HD patient. He was living in the mountains some distance from the village. It was an old house and the family was very poor. Toilet outside the house, no hot water. But the family was extremely kind. Every time when I drove my car, his children were in my car before me. They had never been in a car before.
One day we drove to Banska Bystrica to meet a geneticist, whom he knew. He entered her office and said: a very important man wants to meet you. The doctor (Marta Kvasnicova) was dumbfounded and was willing to meet me. Anyway Marta established the HD Society of Slovakia. I visited her many times and stayed always in her house. A very kind family.

1994: A German lady born in Hungary was so kind to organize a talk at the university of Budapest for me. Unfortunately only one doctor showed up from Pecs in the south part of Hungary. This lead to a visit to Pecs in 1995, where we had a family meeting and a presentation on TV. The doctor invited a what he thought was a HD patient, who he never saw before but she was from a HD family. When I met her, I said for heavens sake she does not have HD but Parkinson! Are you sure Gerrit? Yes, I am. So we had quickly change the TV program. This doctor investigated HD families in the south of Hungary and they found many, many families, which they did not know before. Unfortunately, after a couple of years, this doctor lost interest in HD and the HD society is gone.
But since a couple of years we have new contacts in Hungary, which make sure that HD patients can be helped.

I was invited to attend the HD course for professionals in Atlanta (USA) as guest. I have met very nice and interesting people. The course was very informative. Dinner with Carol Moskowitz was very nice indeed, as a holiday afterwards with my friend Ralph Walker to New Orleans and other places.

1995: A contact with a doctor in Malta. So the 11th IHA meeting in Leuven (Belgium) had three new countries: Hungary, Malta and Slovakia. (In Malta still not a HD society, but a doctor attended our meeting). It was extremely hot in Leuven and no airco. Ralph and I (as usual) had one room. We kept our room door open to try to get some fresh air.

1996: A very busy year: first the establishment of a HD society in the French speaking part (Walonia) of Belgium. A study tour in Finland (payed by the European Union) and organized by our first contact in Finland: Marjatta Sipponen. I visited the academic hospitals in Helsinki and Turku; the rehabilitation centers in Lahti and Masku; a HD family meeting in the MS rehabilitation center in Masku; two lectures at office of the Parkinson society to give them up to date information about HD; a visit of two nursing homes and a couple of HD families.
We decided to establish a HD society and to cooperate with the Parkinson Society, which made it possible to built a rehabilitation center for Parkinson and HD patients in Turku. These centers and societies are sponsored by the so called “slot machine company”. HD is so rare in Finland, that it made no sense to be fully independent.
Two doctors from the university of Helsinki invited me for a sauna visit. It was February and the temperature was about 23 degrees Celsius below zero. In my opinion one should do everything which is possible in one’s life, so for an “extreme cooling down” I jumped in an opening in the ice! It was an experience for sure.

Two ladies from Japan visited me in the Netherlands in order to become updated of the way of testing and counseling, nursing home care etc. This lead to the establishment of a HD society in Japan by Kaori Muto. Kaori was very impressed and years later she said: You changed my whole life.

A man from an HD family from Pakistan visited me in the Netherlands to be informed about all expects of HD and to visit nursing homes in my country. This lead to the establishment of the HD Society of Pakistan,

In between I got in contact with a doctor in Turkey ( Nazli Basak) and with a doctor in Brazil (Freddy Micheli).

1997: The 12th IHA meeting in Sydney, which I could not attend due to the health situation of my father.
New countries: Finland, Japan and Pakistan.

I was contacted by a German lady in Portugal. She was in contact with a HD family and would like more information. When she visited her mother in Germany we met each other. She got the information she needed to support the family. I told her when you support this family, you can also support other HD families in Portugal. It was a rather short talk as she looks not much interested after about two hours. Years later we discovered the reason: we were both smokers and needed a cigarette, but her mother has told her: don’t smoke when you have a visitor!!!

1998: An European meeting in Stirling (Scotland). During a conference dinner a lady (HD patient) was choking. Nobody was doing anything, so I asked may I help you? I did the Heimlich manoeuvre, which was very helpful. Years later she contacted me, because her son (with HD) was living in my country. I asked her: should I know you? She answered: once you saved my life.!!!!

On invitation of Jorge Sequeiros, a doctor in Portugal, I was asked to talk at the occasion of the World Exhibition in Hannover (Germany). I asked Jorge: what kind of public can I expect? Just general people he said. So I prepared a speech for general public. There were two speakers before I was on the ball. It turned out that nearly all persons present were doctors, so I thought: it does not make sense to speak about technical facts of HD. So I improvised a talk about what it means to be a person at risk; to have to make a decision whether or not to be tested; to be a partner of a HD patient etc.

1999: The 13th IHA meeting in Scheveningen (the Netherlands). New country: Brazil.
I got in contact with a lady in Malta (Margaret Panis England) who established the HD Society in Malta and Lydia Veremis from Greece. Lydia, a young lady, translated brochures in Greek. But she and her brother were the only two who were active in Greece. For such young people without financial support and support from professionals a hard job, because they were still also studying.

I got in contact with Jan Kobal, a doctor in Slovenia. On a HD tour in Austria (Vienna, Linz and Graz) I drove to Ljublijana in Slovenia to meet Jan and two people at risk. We decided to have a HD family meeting the next year.

2000: Again to Slovenia for a family meeting. At that meeting we established the HD Society of Slovenia. Cooperation between the Parkinson society and the Huntington society has been arranged. Unfortunately Jan Kobal is the only one who is active now.

A family meeting and meetings with individual doctors in Alvor-Portimao (Portugal). Ulla Kleibrink, who I met at her mother’s in Germany organized the meetings. Good meetings and the establishment of the HD Society in Portugal.

2001: On invitation of the Italian HD Society in Roma attended a meeting between the three independent Italian HD Societies, which had misunderstandings. Within two or three hours all problems were solved. All parties were positive and it was easy to get cooperation between them. People were very kind and showed me Roma (in particular Paola Zinzi).

A remarkable year for me and my family. On the occasion of the 25th anniversary of the Dutch HD society, on nomination of the board of the Dutch Huntington Society (chairman Ineke Lonink), the IHA (president Sue Watkin) and the director of the first HD nursing home in the Netherlands (Wim Nicolaas) I was knighted by Queen Beatrix to Officer in the Order of Oranje Nassau for my national and international work for HD families.

The 14th IHA conference in Copenhagen. New countries: Malta (Margaret Parnis England), Slovenia (Lidya Kores) and Greece (Lydia Veremis).

At the conference dinner our president (Christiane Lohkamp) told the people present (lay and professionals) my knighting. I got from all people a standing ovation, which was extremely nice.

2002: Was a very sad year. I lost my best friend and “adopted brother” Ralph Walker. I attended the memorial service in a church in Cambridge (Canada) and was allowed to talk for about 700 people about our special relationship. Just memories.

The HD Society in Argentina officially established.

Suzanne Boivin and Alexandre Jutras from the Societé Huntington du Quebec (Montreal, Canada) visited several Dutch nursing homes.

Germany
On invitation of Mrs Christiane Lohkamp visited a nursing home/psychiatric clinic in Neumünster and a nursinghome/hospital in Heiligenhafen (Northern part of Germany). I got an address in Neumünster where I should go. I thought that this would be my hotel, so I asked the receptionist for a room. He looked strange at me. Later on it turned out that this address was a nursing home and psychiatric clinic. Nobody before me had asked freely for a room!!!!

Got in contact with a doctor in Cuba (Tatiana Zaldivar Vaillant). She attended the 1st World Congress on HD in Toronto (2003) and established the Grupo Multidisciplinario para la Atencion a Pacientes y Familiares con Diagnostico de Enfermedad de Huntington.

Got in contact with a geneticist in Iran ( Fabiola Hormozian). Unfortunately she got no permission to attend the congress in Toronto. We are still in contact often.

2003: A travel to Istanbul to establish the Turkish HD Society, where we had a fantastic family meeting and a very cordial welcome by Nazli Basak and her assistant.

And a visit to Warsaw in Poland, where doctor Dorota Hoffman, who I have met at the 14th IHA conference in Copenhagen (Denmark) in 2001, just had established the Polish HD Society. I was invited to talk at a symposium of professionals and several times at the family meeting near Warsaw. I stayed with the extreme nice family Hoffman.

After some years contact with Mrs Ana Lucia Heins Molina in Colombia, the HD Society officially established this year.

I was contacted by a HD family member from China who wanted to be tested and asked for information and advise. It turned out that the hospital in Beijing still used the old marker gene test. I got a brainwave, looked and found a geneticist (Dr Lam) in Hong Kong.
Later on I asked him to become the IHA contact person in China. He agreed!
A couple of months later, a Dutch lady living in China was looking for a geneticist and again a couple of months later I was contacted by a social worker in Australia who wanted a test center in China for an Australian lady. Lucky me!

A Japanese neurologist asked me to help him to visit a nursing home with a specialized HD unit. I met him at the railway station and invited him to go to my car. The only thing he said several times was: “woman”. I thought oh my God, he needs a woman! Later on it tuned out that the word “woman” was the only English word he knew and that he was waiting for a lady interpreter who was traveling in the same train.

After having been involved in the organization of the 1st World Congress on Huntington Disease in Toronto (Canada), a lot of problems. First the SAR threat, which made it unsure whether it was possible to held the meeting. When we arrived at Toronto Airport, it turned out that due to an electricity disaster the organizing committee decided to cancel the meeting. They tried to inform all attendees, but people from countries outside North America were already on their way to Canada. Arriving at our hotel, the reception told us that the meeting has been cancelled. That will not happen to us!!! So, the IHA board organized an alternative meeting, which was very, very social, cosy and informative. The IHA is able to improvise!!!!!!!

2004/2005: Due to health problems of myself and serious health problems of my wife and the care for my 100 year old father, my activities were, except the European Huntington meeting and the first meeting of Euro-HD near Madrid in Spain, very limited. Christiane Lohkamp (president IHA) was so kind to take over my visits to family meetings in Czech Republic and Poland.

After many years contact with Dr Roberto Weiser in Venezuela, the Asociacion Venezolana de Huntington official established by Mrs Aleska Gonzalez de Zambrano.

Got in contact with Hany Farid Haleem in Egypt. After many contacts, he agreed to become the IHA contact person in Egypt. I asked him to look for a doctor who is interested in HD and willing to help him to establish a HD Society in his country. Hany and a doctor will attend the 2005 IHA meeting in Manchester.

The HD Society in Peru is still not finished, but I have close contact with Mrs Maria Begazo Viza and with Dr Miriam Velez.

The HD Society in Russia has begun a new life after the leave of Natalya Nikolskaya by a couple doctors (Sergey Klyushnikov and Sergei Illsrioshkin) who attended the European meeting in Spain in 2004.

A Czech neurologist (Jiri Klempir) asked me to help him to find a nursing home with a special HD unit and a neurological institute, where he could stay a couple of weeks to get more experience in caring HD patients.

A delegation from Czech Republic visited two Dutch nursing homes with a special HD unit.

Next to the HD Societies all over the world or societies in establishment, we have also rather close contacts in countries which I did not mention like Chili, Oman, Paraguay, Romania, South Korea, Taiwan, Thailand, Uruguay and Zimbabwe.

At the moment the IHA has 68 Member organizations or close contacts; the IHA mailinglist contains hundreds of persons, most of them working in the HD field, in many, many countries. Regularly they are updated with scientific articles etc.

Looking back, the establishment and development of new HD Societies was rather slowly. The main reason is that first you have to find interested professionals to built up a kind of resource for the HD families and the lay people who have to establish a society. Without the help and support of professionals it does not make sense to establish a HD society. The reality is also, that the lay people are always from a HD family, which make them vulnerable and limited in time and finances, but motivated they are!!!
Next to this, before visiting a family meeting or visiting people (lay and professionals) who are interested in founding a HD society, you must know the culture, the view of life (religion), the legal possibilities etc, which is not always easy.
What started in 1977 with a very short hearing session with the scientist developed in a fully joint congress two years a go. This is unique in the world of international patient organizations of which we must be thankful and proud.

The IHA website had since 26 June 2002 to 26 July 2005: 39812 hits.

Hits per country:
USA 44.1%=17560 Spain 1.5%=600 Austria 0.4%=140
Netherlands 7.5%=3005 Switzerland 1.4%=550 Portugal 0.3%=130
UK 7.0%=2780 Poland 1.0%=400 Denmark 0.3%=130
France 6.6%=2630 Sweden 0.8%=320 Israel 0.3%=120
Canada 5.7%=2280 Brazil 0.6%=260 Finland 0.3%=100
Australia 3.7%=1480 Norway 0.6%=250 unknown 6.3%=2520
Japan 3.1%=1250 Ireland 0.6%=230
Belgium 2.5%=1010 New Zealand 0.4%=170
Germany 2.3%=930 Mexico 0.4%=170
Italy 1.6%=640 Argentina 0.4%=140

On the occasion of this meeting, my farewell of the IHA, I must say that I would thank all my friends within the Huntington community, lay and professional, the many patients and families I have met in all those years in many, many countries, who has given me so much satisfaction; the different members of the board in all those years, which were also very cooperative and the Dutch Huntington Society, which supported me enormously financially to be able to attend all the meetings and the Dutch members who supported the development work for the new HD societies or in establishment with five Guilders per person. As you know that the Dutch Vereniging van Huntington has 1400 members means a nice amount! An initiative never done by any other country.

Manchester, September 2005
Gerrit R. Dommerholt

17th – 20th August 2003

WORLD CONGRESS TORONTO, CANADA, 2003

The search for HD treatments

Dr. Ira Shoulson, (Rochester, New York, USA), presented an overview of research conducted by the Huntington Study Group (HSG). Formed in 1987, and now with 60 active sites and 250 clinical investigators and scientists in the United States, Europe, and Australia, the HSG conducts clinical trials and stores data in a central database. The database contains data collected using the UHDRS (Unified HD Rating Scale), which has been coded to ensure the privacy of participants. Other data, including information on potential biomarkers that may affect disease onset and progression, are also being collected and stored in this database.

A recent phase III clinical trial conducted by the HSG tested two agents, Co-enzyme Q10 and Remacemide, in a double blind placebo study with 450 subjects who had early stage HD. This trial, called CARE-HD (Co-enzyme Q10 And Remacemide Evaluation in HD), found that while neither drug either alone or in combination produced what were considered to be statistically significant improvements, Co-enzyme Q10 slowed the rate of disease progression by about 15%, and Remacemide decreased chorea. Both drugs appeared to be safe and well tolerated. A study of the two drugs at higher doses (2-CARE) is expected to begin in 2004.

Clinical trials of three other drugs: riluzole, creatine, and minocycline are also planned.

In addition to these interventional trials that test the effectiveness of new treatments, the HSG and its partners are conducting two observational trials aimed at better understanding the natural history of the disease. PHAROS (Prospective Huntington At-Risk Observational Study) will run from 1999 to 2007 in the United States and Canada. Individuals who are at risk for HD but have not undergone DNA testing will take part in physical and psychosocial assessments for HD-related features every 9 months. Their DNA will be analysed, but the results will not be revealed. The second observational study, called PREDICT-HD (Neurobiological Predictors of HD) will be conducted from 2002 to 2008 in the United States and Australia. Individuals in the PREDICT study have undergone DNA testing and know the results. The same assessments as are used as in PHAROS are done once a year.

The HSG is supported by Huntington Disease Society of America (HDSA), the Huntington Society of Canada (HSC), the Hereditary Disease Foundation (HDF), the High Q Foundation and the National Institutes of Health (NINDS, NHGRI).

Dr Bernhard Landwehrmeyer (Germany) added that a European HD Research Network has been formed with funding from the High Q Foundation. The network will cover Italy, UK, Germany, The Netherlands, France and Sweden; and it will establish a similar and compatible clinical database as the one set up by the HSG. The Network plans to run Phase 2 (tolerability) trials of three compounds, with one commencing in 2004.They also plan to look for biomarkers and conduct a PREDICT-type study, which will include PET scans. The stakeholders’ committee for the European network will include consumer representatives.

Human Experimental Therapies

Dr Marc Peschanski, (Creteil, France), discussed neurosurgical approaches to treating HD that aim to correct the loss of neurons that occurs in the brains of people with HD. After initial promising results in animal studies, five early stage HD patients received transplants of fetal brain cells. The hope is that these transplanted cells will form new neural connections to compensate for damaged areas of the brain. Of the initial five subjects, one did not improve; one initially improved but then regressed, and three showed sustained physical and cognitive improvement after 12 months. Peschanski said the trial will be expanded to 50 patients across 7 centres in Europe; and it is hoped the trial will be completed by 2007. Another neurosurgical approach uses gene therapy to insert genes for neuroprotective agents into brain cells. Phase I clinical trials have shown this approach to be safe and feasible, however further clinical studies will be needed to determine whether this approach is effective.

Maurice Curtis, (Auckland, New Zealand) presented research showing that new neurons are generated in the brain of individuals with HD. This research offers hope that there may be ways of replacing damaged brain tissue by encouraging undifferentiated stem cells to differentiate into neurons.

Dr Krishna Vaddadi and Dr Philip Dingjan, (Melbourne, Australia), discussed an approach to treating HD with essential fatty acids. Highly unsaturated fatty acids (HUFA) exist in high concentrations in the brain, and have been implicated in a number of neurodegenerative disease. In animal and human studies, treatment with essential fatty acids containing Ethyl-eicosapentaenoic acid (EPA) has appeared effective in treating motor abnormality. Vaddadi and Dingjan presented a single case example from a study they are conducting using EPA to treat patients with HD. They used cognitive measures to assess progression of HD, since these measures have been shown to be among the most sensitive indicators of progression and correlate well with imaging studies. Over a six-year treatment period, the patient showed little variation in scores on cognitive tests, indicating a lack of deterioration and suggesting that HUFA therapy has been clinically beneficial.

Dr Raphael Bonelli (Graz, Austria) analyzed all available double-blind, placebo controlled studies on therapy in HD, including relevant open trials and case reports, and concluded that these trials focus on the treatment of chorea, but ignore features of HD such as dementia, depression, and psychosis. Bonelli and colleagues recommend riluzole, olanzapine, and amantadine for the treatment of movement disorders associated with HD; SSRIs and mirtazapine for the treatment of depression; and atypical anti-psychotic drugs for psychosis and behavioural problems. Optimal management should also include psychotherapy, physiotherapy, and speech therapy.

Clinical Characteristics

Dr David Craufurd (Manchester, UK) and colleagues have investigated libido and sexual behavior in individuals with HD. While many previous studies have suggested that HD is associated with hypersexuality, Craufurd found that loss of libido and hyposexuality are much more common and correlate strongly with other measures of disease progression. They concluded that hypersexual behaviour is rare in HD and affects only a small minority of people.

Dr Julie Snowden, (Manchester, UK) reviewed longitudinal studies that have assessed cognitive impairment in people with HD. These studies consistently showed that psychomotor tasks (such as the Stroop test and Trail making) are most sensitive to changes in cognitive function; and that tests of executive function, memory, and general intellectual function are poor indicators of cognitive decline. Snowden’s own research with asymptomatic people who carry the HD mutation supports this finding. She concluded that simple psychomotor tests are the best tools for measuring change in HD and for use in clinical trials.

Dr Elizabeth Howard, (Manchester, UK), described two simple objective measures that can be used to evaluate motor progression in HD. These assessments are needed because tests of motor function that are currently used in the Unified HD Rating Scale (UHDRS) have shown limited usefulness in longitudinal studies because of variations in chorea from one appointment to the next and the effect of emotional state on the severity of involuntary movements. In the first of these two measures, patients are timed as they walk a fixed distance (including a 180-degree turn) as fast as they can. For the second assessment, they are timed as they drink 130 mls. of water as fast as possible. Both of these tests showed significant correlation with the duration of illness and between the two measures themselves. Both tests can be conducted with non-medical personnel and require no special equipment. They can be used as simple and reliable additions to the motor scale portion of the UHDRS.

Jennifer C Thompson (Manchester, UK), has developed a new task designed to measure the ability of people to make social inferences. Altered social conduct and a breakdown in interpersonal relationships are prominent features in HD. Tests of “social cognition” have attempted to measure a person’s ability to interpret social situations or ascribe mental states to others; however these tests are difficult to use in patients with cognitive impairments because they often make demands on attention and memory. Thompson’s test minimizes these demands by presenting simple, illustrated vignettes that depict everyday social situations. Patients are asked a series of questions that tap their ability to understand the beliefs, thoughts, and feelings of the characters shown in the vignettes, and to draw inferences about the social situations that necessitate going beyond the information given. HD patients given this test were particularly impaired in the ability to draw inferences from social situations. This finding may help explain the breakdown in social behavior among people with HD.

Dr Kristy Bolter (Wellington, New Zealand) described experiments designed to study memory and learning in people with HD. Other studies have shown that people with HD perform poorly on tests of learning and memory. Bolter designed a learning task that does not require good motor function to achieve success. Her results show that patients in the mid-to-later stages of disease have trouble with sequential learning (learning the steps required to accomplish the task) but still have good implicit memory (learning based on unintentional recall of experiences). Her second experiment suggested that poor performance on explicit memory tasks may be due to difficulty retrieving information from memory.

Nellie Georgiou-Karistianis (Melbourne, Australia) showed that people with HD have particular trouble shifting and directing their attention away from various stimuli. His findings support the notion that the cognitive deficits in HD may stem from abnormalities of the major pathways interconnecting the basal ganglia and the frontal lobes of the brain.

Genetic Counseling

Ms Alison Lashwood (London, UK) discussed outcomes in nine couples who have undergone pre-implantation genetic diagnosis (PGD) for HD since the practice became available in the UK in May, 2002. Four couples became pregnant, but one miscarried triplets. One couple had twins and two have ongoing pregnancies. Five couples have not achieved pregnancy.
PGD raises a number of complex ethical issues, including concerns about the welfare of a child born into a family where one parent will become symptomatic. In addition, there is a misdiagnosis risk of 2-5% per embryo. Yet none of the couples who achieved pregnancy chose to have confirmatory prenatal diagnosis; and no confirmatory testing is done at birth. Despite these complexities, PGD offers an acceptable alternative to routine prenatal diagnosis.

Oliver W Quarrell (Sheffiield, UK) examined outcomes in a group of at-risk individuals with between 36 and 39 CAG repeats, as determined by predictive testing. People with repeat lengths in this range may or may not develop the condition. At least 170 individuals tested in the UK had repeat lengths in this range. At the time of this presentation, data had been collected on 41 of these individuals. Twenty-six are affected, with age of onset ranging between 38 and 80 years. Fifteen are asymptomatic, with ages ranging between 35 and 71 years. Data collection was expected to continue throughout 2003.

Fiona Richards (Sydney, Australia) studied the reproductive decisions of 373 adults who underwent predictive testing for HD in Sydney, Australia, between 1990 and 2002. As has been shown in previous research, prenatal testing and other reproductive options are used in a minority of individuals who get predictive testing. Prior to predictive testing, nearly 60% of these individuals had pregnancies. Three chose to have prenatal testing and four chose alternative reproduction options (e.g., adoption or in vitro fertilization). Among those individuals who were in the reproductive age group (18-45 years), 47% were found to be carriers of the HD mutation and 53% were non carriers. Regardless of the results of predictive testing, about 30% went on to have pregnancies. Only 17% of the carriers who became pregnant had prenatal testing done; and as a result four pregnancies were terminated. Among 24 carriers who were symptomatic at the time of testing, three had pregnancies, one of which was terminated. None had prenatal testing done. Two carriers and two non-carriers used alternative reproductive options.

Ms Roslyn Tassicker (Melbourne, Australia) discussed the challenging counseling and legal issues presented by non-consensual predictive testing, in which predictive testing is requested of someone who does not want to know the results. For example, two requests were received for prenatal testing by women whose partners are at 50% risk but do not want testing. However, a positive prenatal result would reveal that the partner does, indeed, carry the gene. Another thorny situation arises when a person at 25% risk (because one parent is at 50% risk) requests predictive testing although the parent does not want to know the results. At present, there is no clear legal advice for most of these situations, but guidelines recommend involving both parties in counseling if possible. Other situations included two cases of identical twins where one twin wanted testing and the other did not. Legal advice was to go ahead with the tests, while warning the non-tested twins of possible harm and encouraging them to seek support from genetic services.

Ferdinando Squitieri (Pozzilli, Italy) studies people who are homozygous for the HD mutation. This condition is rare and little is known about the effect on severity; yet different genetic counseling strategies are needed for this group of people, particularly when they come from communities where marriage among relatives is common. Squitieri identified 14 subjects. Two are presymptomatic, yet their offspring will have a 100% risk of inheriting the mutation; and their siblings have a 75% risk. He has established a tissue bank and is studying the biological differences between cells from people with homozygous versus heterozygous mutations. Results from this study show that age of onset was similar for homozygotes, but the clinical course was more severe, with a more rapid decline in motor, cognitive, and behavioral symptoms and more extensive neurodegeneration. Squitieri speculated that the more severe phenotype may result from higher levels of the mutated protein, more aggregate formation, and more sequestration of critical cellular components. Alternatively, homozygosity may reflect a loss of the neuroprotective function of the wild-type protein that would be produced in heterozygotes. These data, once confirmed in a larger series of patients, point to the possibility that the mechanisms underlying age at onset and disease progression in HD may differ.

Social and Historical Perspectives on HD

Dr Kaori Muto, (Nagano, Japan) discussed issues related to HD in Japan. The prevalence of HD in Japan is 1 per 100,000 compared with 6 per 100,000 in populations of European origin. In 2001 there were 604 people with HD in Japan. The government and medical insurance systems cover basic medical costs of HD. Many medical institutions provide predictive testing (without genetic counseling,) even though the guidelines of academic societies do not allow prenatal genetic testing and pre-implantation genetic testing. The Japanese HD Network (JHDN) is a web-based support group for HD families. A survey was given and interviews conducted with some members of JHDN. Most at risk people had not had predictive testing. Many had kept HD as a family secret and were unsure about how and when to tell their children about HD. The main concern for people at risk is discrimination in marriage prospects. Caregiving is another important issue. Some of the efforts that have been taken to raise awareness of HD in Japan have included: Translation of Alice Wexler’s book ‘Mapping Fate’ into Japanese; a TV documentary on HD in September 2003 (first ever shown on Japanese TV); and translation of UHDRS into Japanese so Japanese clinicians can contribute to HSG research.

Who killed that lady? A HD murder case in Japan
Dr. Muto described a case in which a 72-year-old male caregiver murdered his 55-year-old wife with HD, by strangulation in 2002. Muto and colleagues conducted a study to clarify the circumstances around this murder. They examined written statements and interviewed health care professionals involved in this case as well as the accused husband. The man had cared for his wife at home for seven years since she started to show symptoms. He had a poor understanding of HD, in part because of information her physician had given him. For example, he had been told that people with HD die within 6 or 7 years. He thought she was in a terminal stage, although she was not. Over time, he lost hope in his ability to both work and care for her, although he tried to maintain his reputation in his neighborhood as a good caregiver who manages everything himself. Muto concluded that the woman’s murder could have been prevented if her physicians and local health professionals had worked with the Japanese Huntington's Disease Network (JHDN) to learn more about the disease and support the woman and her husband. However, in Japan it rare for a lay organization to support local health professionals. A pilot model should be developed to provide this support for people with HD, their families, and health professionals

Psychosocial Issues

Karen Keast (Sydney, Australia) discussed several innovative approaches developed by dietitian and speech pathologists from the NSW Huntington Disease Service to make texture-modified diets more acceptable, and thus, to reduce the impact of such diets on people’s quality of life. These efforts began with a resource package called “Shop to Swallow,” which listed a range of foods available in the supermarket that are soft, minced, or pureed. Purchasers found the resource useful. Keast and her colleagues are also preparing a similar resource that lists soft, minced, or pureed foods that are available at fast food outlets. Finally, they conducted a study to evaluate the appeal and usefulness of pureed food moulded to more closely resemble typically prepared foods. Eight adults with impaired swallowing and 8 adults with unimpaired swallowing rated a range of pureed food items and a range of moulded food items. The attributes rated included overall liking; liking of taste, texture and appearance; and ease of chewing and swallowing. Moulded pureed meals show promising preliminary results in enhancing the visual presentation of texture modified food without compromising taste and ease of swallowing.

Dr Sheila Simpson (Aberdeen, Scotland) discussed some of the ethical issues that arise when percutaneous endoscopic gastrostomy (PEG, or tube feeding directly into the stomach) is suggested for patients in the end stages of HD. PEG tubes are often put into place with little or no discussion about the risks and benefits with the patient or family. In a survey of members of Scottish HD families, only 6.9% had discussed PEG feeding with their doctor. Simpson recommended that patients and their families make decisions about PEG feeding well ahead of the time when it may be needed; and also investigate having a ‘living will’ and/or ‘power of attorney’. International guidelines would also be useful.

Genetics

Dr David Rubinsztein (Cambridge, UK) reviewed recent advances that have changed what scientists think about the genetics of HD. First, while HD is considered to be inherited in a true dominant fashion, meaning that a person with only one mutant allele is as affected as someone with two mutant alleles, recent data suggests that the disease may progress more rapidly in people with two mutant alleles. Second, recent evidence suggests that one of the ways the HD gene may cause problems is by interfering with the ability of the normal protein to bind with other proteins. Third, while the size of the HD mutation largely predicts age of onset, recent data suggest that there are genetic modifiers in humans that affect age of onset.

Ferdinando Squitieri (Pozzilli, Italy) discussed a study of 57 patients with juvenile HD. He analyzed how the gender of the affected parent influence age of onset and clinical presentation, as well as molecular features of the disease including CAG mutation length and GluR6 gene polymorphism. While the mutation length was longer in people who inherited the mutation from their fathers, there was no change in age of onset. There were, however, polymorphisms in the GluR6 gene that influenced age of onset in juvenile patients. Squitieri’s findings suggest that the paternal mutation has a weak effect on age at onset in the juvenile population, but that it may be amplified by other genetic factors.

Pathogenetic Mechanisms

Dr Patrik Brundin and Dr Asa Petersen (Lund, Sweden) summarized research from their laboratories and others that point to cell dysfunction, rather than cell death, as the cause of HD symptoms, and thus the most promising target for intervention. They based this conclusion on work done in the R6/1 and R6/2 transgenic mice, which are widely used as models of the human condition. Like humans with HD, these mice develop motor and cognitive impairments, and the age of onset is inversely correlated with the length of the CAG repeat. However, unlike humans with HD the R6 mice show little neuronal death, suggesting that neuronal loss is not the cause of symptoms. Brundin and Peterson have shown that neurons of these mice undergo gradual changes in function and a reduced ability to generate new neurons in the hippocampus. R6 mice show other signs of illness outside the nervous system, including weight loss, changes in their ability to regulate blood surgar, insulin resistance, and other endocrine changes. These observations suggest that mutant hungtingtin may cause widespread cellular dysfunction. Prevention of cell dysfunction, rather than just cell death, should be considered when developing therapies.

Acknowledgements:
Robyn Kapp, AHDA(NSW), Australia
Fiona Richards, The Children’s Hospital Westmead, Australia
2003 WCHD Congress Program Book