HD Therapeutics Conference 2013 Updates: Day 1
Day 1 of our coverage of the Huntington's Disease Therapeutics Conference
By Dr Jeff Carroll April 09, 2013 Edited by Professor Ed Wild
Our first daily report from the annual Huntington’s Disease Therapeutics Conference in Venice, Italy. We’ll be bringing you live updates via Twitter over the next two days. You can use HDBuzz.net, comment on Facebook or tweet @HDBuzzFeed to send us questions, comments and queries.
9:00 - Buonasera from Venice, where HDBuzz will be tweeting the latest Huntington’s disease research news from the annual therapeutics conference
9:08 - Huntington’s disease therapeutics conference kicks off with a session on systems biology
9:09 - Systems biology tries to understand networks of connected chemicals and processes, rather than focusing narrowly on one thing
9:10 - The hope is that this systems approach will help us better understand Huntington’s disease and develop and test treatments
9:12 - Robert Pacifici of CHDI: one tiny change, the HD mutation, causes lots of changes in the biology of people who carry it
10:35 - Jim Rosinski of CHDI: new technologies are being used to get better understanding of HD, like RNA sequencing - what genes are on/off
10:38 - Rosinski: “Amazing things are possible now” and the HD gene gives us a head start for understanding the disease
10:38 - HD drug development company CHDI is integrating techniques from engineering and computer science to better understand HD
12:10 - Lesley Jones is studying HD mice to understand how much they look like HD patients. In many important ways they’re similar.
12:16 - William Yang is using mouse brains to map out which proteins the HD protein interacts with. More targets for drug developers
12:29 - Collecting all this data from HD patients and animals poses computational challenges, that Steve Horvath is working hard to fix
12:43 - With nearly 300 researchers attending, this is the biggest ever HD therapeutics conference
14:33 - Why do we have an HD gene at all? Elena Cattaneo is studying diverse animals, including sea urchins, to try to understand
14:53 - According to Dr Cattaneo, the normal HD gene seems to have important roles during the development of the brain
15:10 - If the HD gene is important for brain development, what happens in brains of people born with the HD mutation? Peg Nopoulos studies this
15:11 - Nopoulos’ HD-KIDS study follows school-age kids at risk for HD. Gene testing is done without anyone involved finding their result
15:14 - Nopoulos: major brain changes occur throughout childhood
15:19 - Nopoulos: KIDS-HD allows us to study not just HD but also the role of huntingtin in normal brain development
15:20 - Even in HD-negative people, there is variation in the number of CAG repeats in the huntingtin gene.
15:25 - In kids who don’t have the HD mutation, some aspects of thinking and behavior are subtly influenced by CAG repeat length.
15:28 - Some brain areas are also affected by the number of CAG repeats in the HD gene - in kids who are NEGATIVE for the HD mutation.
15:29 - Fascinating insights into the core mystery of Huntington’s disease from Nopoulos: what does the normal huntingtin protein do?
15:33 - In kids who DO carry the HD mutation, Nopoulos finds subtle changes that are compensated for, but are their brains more vulnerable?
15:50 - Audience question from statistician raises concerns that statistical methods used to test Nopoulos’ data may not be rigorous enough for small sample
16:25 - Jeff Macklis of Harvard studies the neurons connecting brain’s cortex (crinkly surface) to the basal ganglia (movement control bit)
16:44 - Macklis: understanding of how different cell types become neurons and how they function has improved dramatically in past 5 years
17:16 - Ali Brivanlou of Rockefeller University is an expert on human development. Huntingtin protein is found in the very earliest embryo cells
17:17 - Using RNA sequencing, Brivanlou has identified 4 new RNA message molecules for huntingtin in embryo cells. These could produce new proteins
17:18 - Brivanlou’s ‘new’ huntingtin molecules are created by reading the huntingtin gene in different ways to create ‘spliced’ RNA messages
17:20 - The function of these new huntingtin forms in embryonic cells is not known. Remember we’re talking about normal, not mutant huntingtin here.
17:31 - Brivanlou: Embryos without huntingtin die after a week of development, but why? It changes the response to growth molecules
17:34 - Brivanlou: huntingtin has an influence on the metabolism of embryos - that’s how they use energy & do chemical reactions.
17:38 - Brivanlou: in embryos with the HD mutation, sugar metabolism is unexpectedly altered. It’s unclear whether this affects development
17:43 - Today’s biggest news: Roche & Isis sign $30million deal to take gene silencing drugs for HD to trials
On the opening day of the biggest ever Huntington’s disease therapeutics conference, we heard a lot about studying the complexities of the brain, and the role of the huntingtin protein, still mysterious twenty years after its discovery - but not very much about drugs. But understanding how the brain develops and works, and ‘knowing the enemy’ - the mutant huntingtin protein and its damaging effects - are both crucial if we are going to safely and rapidly develop the treatments we’re all working towards. You never know where the next big idea will come from, and it’s from fundamental, imaginative research of the kind we’ve hear about today that bright new ideas for possible treatments may well spring up.