World Congress

Highlights from the 2013 World Congress on Huntington’s Disease

By: Débora Palma Maia, MD

brazilThe 2013 World Congress on Huntington’s Disease in Rio de Janeiro, Brazil, brought together physicians, scientists, health professionals, patients, family members and support groups to share new knowledge, with the goal of improving the management of HD.

Congress activities began with talks by members of various HD patient organizations. Mr. Rodrigo Osorio, president of Agrupación Chilena de Huntington, described the Red Latinoamericana de Huntington, a network of HD clinics in Latin America (see HD Insights, Vol. 5). It is estimated that 40,000 Latin Americans have HD. This large number of HD patients could help professionals, patients and families to better understand the disease. Mr. Matt Ellison, founder of the HD Youth Organization (HDYO), tackled the challenges faced by young people at risk for HD. He described how the HDYO website may help reduce the stigma of HD by educating young people and families.

In the “Basic Science” session, Dr. Elena Cattaneo described the emergence of huntingtin 800 million years ago, noting that this protein plays a crucial role in the development of brain cells through the formation of structures called rosettes. According to Dr. Marcy MacDonald, the development of HD is a lifelong process, unrelated to prions or prion-like processes. Finally, Dr. Ignacio Muñoz-Sanjuan described how PDE10A inhibitors can reduce the overexcitable properties of medium spiny neurons (see HD Insights, Vol. 5).

The second day of the Congress focused on premanifest HD. Drs. Alexandra Durr and Karl Kieburtz shared their experiences in TRACK-HD and PREDICT-HD, which found that brain imaging is a powerful technique for measuring HD progression. Cognitive tests such as the Symbol Digit Modalities Test are also good measures of progression. Dr. Ralf Reilmann, a movement disorders specialist, reviewed quantitative motor assessment, and argued that movement changes in premanifest subjects can be detected many years before symptoms begin, and are good measures of HD progression (see “Selected by Chance,” p. 1). However, he pointed out that some early movement changes in carriers of the HD mutant gene do not mean that individuals with these movement changes are sick. Prof. Julie Stout reported similar findings for cognitive functions.

Dr. Peggy Nopoulos discussed clinical findings in juvenile HD, and Dr. Francisco Cardoso spoke about the differential diagnosis of HD. He explained that in around 1% of cases, genetic testing does not reveal a CAG expansion. These cases are called HD-like disorders. One of them, HD-like-2, has a phenotype very similar to HD and it is more common in people of African descent. He reminded attendees, however, that these conditions are rare.

Dr. James Gusella presented genetic factors that could influence the age of symptom onset in individuals who are carriers of the HD mutant gene. He believes that understanding the mechanism of the manifestation of symptoms could make it possible to delay their onset. Dr. Laura Jardim discussed the genetic aspects of HD specific to Latin America, a continent with a complex genetic background derived from the population’s Indigenous, European and African genetic ancestries.

Drs. Sarah Camargos and Mônica Haddad presented ENROLL-HD, a global observational study of HD that aims to enroll as many people as possible. They discussed the importance of sharing data, and argued that ENROLL-HD may help to further understanding of the disease, and to educate health professionals around the world about better methods of care for HD patients.

The last Congress session discussed novel therapies. Dr. Douglas MacDonald told the Congress, that there is a “rich pipeline of therapeutics” advancing into the clinic. Dr. MacDonald’s group is working in particular with antisense oligonucelotides to silence the Huntingtin gene, and he told the Congress about emerging gene silencing techniques (see HD Insights, Vol. 3). Dr. Neil Aronin presented his group’s efforts to use deactivated viruses to silence the mutant HD gene. These gene-silencing approaches have shown great promise for the near future. Dr. Bernhard Landwehrmeyer gave an update on clinical trials in HD, while Dr. David Craufurd discussed drug treatment for psychiatric symptoms that is often necessary, and Dr. Binit Shah described deep brain stimulation in HD. At the end of the Congress, Dr. Joaquim Ferreira offered an encouraging reminder that while there is currently no cure for HD, there are a number of treatments that help patients, and many more that show great promise are on the horizon.

Highlights from the World Congress on HD

By: Mahmoud Pouladi, PhD

highlights

The four-day conference was held in Melbourne, Australia

The 2011 World Congress on Huntington’s Disease in Melbourne, Australia, brought together HD clinicians, basic scientists, patients, families, and support groups. Peter Harper and Sarah Tabrizi gave the opening addresses.

Peter Harper presented historical highlights of HD, emphasizing the uniqueness of the HD community among other neurodegenerative disease communities. He said the HD community should take pride in the closeness that exists between HD scientists, clinicians, patients and patient families. He ended his presentation with the idea that HD should no longer be regarded as untreatable, given the current state of research and understanding in the HD community.

Sarah Tabrizi spoke about HD disease pathways and mechanisms that are currently the subject of therapeutic efforts. She said that many pharmacological candidates targeting these pathways will be entering clinical trials over the next two years. She presented findings from the TRACK-HD study, in which various measures, particularly those of brain atrophy, showed significant deterioration over a 1-2 year period. The results indicate that therapeutic interventions in early HD may be possible. Professor Tabrizi also announced the launch of a new study, TrackOn-HD, which aims to investigate neural compensatory mechanisms that may delay cognitive decline in HD gene carriers.

Colin Masters revealed Prana Biotechnology’s plans to conduct clinical trials of their metal chelator PBT2 as a treatment for HD. Abnormal interactions between copper and/or iron and mutant huntingtin in the brain of HD patients have long been suspected, and treatment with PBT2 may benefit these patients. Clinical trials of PBT2 are scheduled to commence in late 2011 in Australia and the USA.

Three scientists presented their efforts to reduce levels of mutant huntingtin in HD gene carriers and clinical patients. Frank Bennett from Isis Pharmaceuticals presented an update on the company’s efforts to silence the mutant huntingtin allele, using antisense oligonucleotides (ASOs). Don Cleveland presented data that indicate that short-term silencing of expression of mutant huntingtin using ASOs is sufficient to improve phenotypes in a mouse model of HD. Beverly Davidson presented her findings on shRNA and miRNA – mediated approaches to silencing the expression of mutant huntingtin in mice and rhesus monkeys. In the monkeys, the reduction of endogenous huntingtin levels in the posterior putamen had no adverse effect on measures of motor function and learning.

Anthony Hannan discussed the influence of environmental factors on HD disease progression. Dr. Hannan and his colleagues have used mouse models of HD to demonstrate that environmental enrichment stimulates hippocampal neurogenesis, and enhances synaptic function in HD. He suggested that environmental or pharmacological interventions that strengthen synaptic function should be pursued as potential HD treatments.

Paul Muchowski spoke about the peripheral effects of mutant huntingtin on central HD pathology. He presented data suggesting that pharmacological modulation of molecular targets (i.e. antagonism of kynurenine 3-monooxygenase or agonism of cannabinoid receptor type 2) in the periphery could be beneficial in HD.

Robert Pacifici presented CHDI’s vision for a target-based, hypothesis-driven approach to drug discovery in HD. He pointed out that different animal models of HD may be useful for modeling different aspects of HD, and that there is no such thing as a ‘good’ or ‘bad’ animal model. He also talked about the value of exploratory studies and observations made in HD patients, echoing the call for participation of HD gene carriers and patients in clinical research.

Michael Hayden discussed the changing prevalence of HD. He said that the increase in the proportion of elderly people in the global population is likely to increase the prevalence of HD and its associated burden.

The Congress also featured perspectives on international models of HD care from Daniela Rae (Europe), Andrew Churchyard (Australia), Amanda Krause (South Africa), Francisco Cardoso (South America), Darshana Sirisena (Sri Lanka).

Robi Blumenstein gave the Congress closing presentation, and outlined the three elements he believes will be essential for a successful HD trial: an effective treatment; methods to measure the positive effects of treatment; and the active participation of HD gene carriers in clinical research.