HD Therapeutics Conference 2012 Updates: Day 2
Day 2 of our coverage of the Huntington's Disease Therapeutics Conference
Our second daily report from the annual Huntington’s Disease Therapeuticstherapeutics treatments Conference in Palm Springs, California. The second day’s sessions focused on gene silencinggene silencing An approach to treating HD that uses targeted molecules to tell cells not to produce the harmful huntingtin protein. You can tweet @HDBuzzFeed or email palmsprings@hdbuzz.net with your questions, comments and queries.
Wednesday, February 29, 2012
9:03 – HD Therapeuticstherapeutics treatments Conference Update: This morning is focused on gene silencinggene silencing An approach to treating HD that uses targeted molecules to tell cells not to produce the harmful huntingtin protein – a very exciting potential therapy. Stand by!
Image credit: Open Street Map
9:35 – Beverly Davidson (University of Iowa): silencing the mutant HD gene in mice has clear benefits, but we need to consider any unintended toxic effects
9:45 – Davidson is behind one of three recent papers showing huntingtin gene silencinggene silencing An approach to treating HD that uses targeted molecules to tell cells not to produce the harmful huntingtin protein safe in primates – a key step to human trials
9:49 – Davidson’s team is now working on new gene silencinggene silencing An approach to treating HD that uses targeted molecules to tell cells not to produce the harmful huntingtin protein drugs that silence the mutant copy of the gene more than the ‘healthy’ copy.
9:50 – Targeting the mutant gene selectively might be safer but is more challenging. Both approaches are being worked on.
10:06 – Frank Bennett (Isis Pharmaceuticals) uses slightly different DNA-like molecules called ASOsASOs A type of gene silencing treatment in which specially designed DNA molecules are used to switch off a gene to silence the Huntingtin gene
10:07 – Bennett: Huntingtin seems to be relatively easy to silence compared to other genes – lucky break!
10:00 – Bennett’s ASOASOs A type of gene silencing treatment in which specially designed DNA molecules are used to switch off a gene drugs are absorbed into cells better then RNAiRNA interference A type of gene silencing treatment in which specially designed RNA molecules are used to switch off a gene drugs. Might make it easier to get to patients – no brain surgery?
10:13 – Bennett’s company Isis pharmaceuticals is experienced in gene silencinggene silencing An approach to treating HD that uses targeted molecules to tell cells not to produce the harmful huntingtin protein – 2,000+ patients with other diseases have received their drugs
10:17 – Bennett: when tested in 2 different HD mouse models, ASOASOs A type of gene silencing treatment in which specially designed DNA molecules are used to switch off a gene gene silencinggene silencing An approach to treating HD that uses targeted molecules to tell cells not to produce the harmful huntingtin protein drugs produced improvements in coordination and cognition
10:19 – Bennett: infusion of ASOASOs A type of gene silencing treatment in which specially designed DNA molecules are used to switch off a gene into the fluid at the base of the spine in primates is enough to get the drug to large areas of the brain
10:22 – Bennett: even one-off injections of the gene silencinggene silencing An approach to treating HD that uses targeted molecules to tell cells not to produce the harmful huntingtin protein ASOASOs A type of gene silencing treatment in which specially designed DNA molecules are used to switch off a gene may be enough to treat the brain. But deep brain regions harder to reach
10:25 – Bennett: many people have small spelling differences, apart from the expanded CAG, between the 2 copies of Huntingtin gene. These differences can be targeted, to design drugs that silence only the mutant gene.
11:04 – Steve Zhang (Sangamo BioSciences): ‘zinc finger proteins’ can bind to specific DNA sequences, raising the possibility of ‘editing’ our genes
11:07 – For anyone wanting more detail, video of the talks will be available online soon, and we’re writing a summary article too
11:00 – Zhang: other uses of zinc finger proteins include designing stem cellsstem cells Cells that can divide into cells of different types to study generic diseases in human cells
“Many people have small spelling differences, apart from the expanded CAG, between the 2 copies of Huntingtin gene. These differences can be targeted, to design drugs that silence only the mutant gene.”
11:18 – Zhang’s company Sangamo has successfully treated hemophilia in a mouse model using ‘genome editingGenome Editing The use of zinc-finger nucleases to make changes in DNA. 'Genome' is a word for all the DNA we each have.’
11:19 – Zhang: Zinc fingers can also be used to switch genes on and off, another possible approach to gene silencinggene silencing An approach to treating HD that uses targeted molecules to tell cells not to produce the harmful huntingtin protein
11:20 – Zhang: we could also try to switch on helpful genes, so that the brain produces more protective chemicals
11:25 – Zhang: zinc finger drug that makes the brain produce the protective chemical GDNFGDNF glial cell-derived neurotrophic factor: a growth factor that protects neurons in Parkinson’s Disease, and maybe HD is about to start a trial in Parkinson’s disease
11:26 – Sangamo is now involved in Huntington’s disease research.
11:29 – Zhang: Sangamo’s current strategy is to try to reduce Huntingtin production with a tailor-made zinc finger drug
11:36 – Zhang: they’re also working on a zinc finger silencing drug that only works on huntingtin genes with expanded CAG repeats
11:53 – Bill Kaemmerer (Medtronic): To make new silencing trials happen we need ‘biomarkers’- tests of safety & measurements to tell us if it’s working
12:02 – Kaemmerer: A combination of MR imaging, CSFCSF A clear fluid produced by the brain, which surrounds and supports the brain and spinal cord. chemicals and clinical measures will be used for early RNAiRNA interference A type of gene silencing treatment in which specially designed RNA molecules are used to switch off a gene gene silencinggene silencing An approach to treating HD that uses targeted molecules to tell cells not to produce the harmful huntingtin protein trials
12:07 – Kaemmerer is part of the team behind another recent primateprimate a group of mammal species including monkeys, apes and humans safety trial of huntingtin gene silencinggene silencing An approach to treating HD that uses targeted molecules to tell cells not to produce the harmful huntingtin protein
12:37 – Neil Aronin (University of Massachusetts School of Medicine) and his team are trying to understand how one gene silencinggene silencing An approach to treating HD that uses targeted molecules to tell cells not to produce the harmful huntingtin protein approach, RNAiRNA interference A type of gene silencing treatment in which specially designed RNA molecules are used to switch off a gene, works in great detail to design good drugs
12:46 – Aronin and his team are are using sheep to practice the neurosurgical techniques needed for gene silencinggene silencing An approach to treating HD that uses targeted molecules to tell cells not to produce the harmful huntingtin protein trials in humans
Sunset conclusions
Several different strategies are being developed in parallel to ‘silence’ the huntingtin gene that’s the ultimate cause of all problems in HD. There are a few wrinkles to iron out, but basically so far each approach has cleared every hurdle it’s encountered. Several clinical trials involving HD patients are being planned, all aiming for a rapid start – within months rather than years. The stakes are high, but it’s a genuinely exciting time.
Learn more
Sources & References
For more information about our disclosure policy see our FAQ…
