By: Mahmoud Pouladi, PhD
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.