HD Therapeutics Conference 2012 Updates: Day 2

Our second daily report from the annual Huntington’s Disease Therapeutics Conference in Palm Springs, California. The second day’s sessions focused on gene silencing. You can tweet @HDBuzzFeed or email palmsprings@hdbuzz.net with your questions, comments and queries.

Wednesday, February 29, 2012

9:03 – HD Therapeutics Conference Update: This morning is focused on gene silencing – a very exciting potential therapy. Stand by!

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 silencing safe in primates – a key step to human trials

9:49 – Davidson’s team is now working on new gene silencing 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 ASOs 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 ASO drugs are absorbed into cells better then RNAi drugs. Might make it easier to get to patients – no brain surgery?

10:13 – Bennett’s company Isis pharmaceuticals is experienced in gene silencing – 2,000+ patients with other diseases have received their drugs

10:17 – Bennett: when tested in 2 different HD mouse models, ASO gene silencing drugs produced improvements in coordination and cognition

10:19 – Bennett: infusion of ASO 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 silencing ASO 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 cells to study generic diseases in human cells

11:18 – Zhang’s company Sangamo has successfully treated hemophilia in a mouse model using ‘genome editing’

11:19 – Zhang: Zinc fingers can also be used to switch genes on and off, another possible approach to gene silencing

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 GDNF 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, CSF chemicals and clinical measures will be used for early RNAi gene silencing trials

12:07 – Kaemmerer is part of the team behind another recent primate safety trial of huntingtin gene silencing

12:37 – Neil Aronin (University of Massachusetts School of Medicine) and his team are trying to understand how one gene silencing approach, RNAi, 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 silencing 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.

Share on facebook
Share on twitter
Share on pinterest
Share on email

Latest Research Articles

HD and Histamines: Targeting Hybrid Receptors to Quiet Stressful Brain Talk

Published date: 15 July, 2020

Dopamine is an important chemical messenger in the brain that becomes imbalanced in Huntington’s disease. Researchers recently described a creative way to restore the balance and treat symptoms in HD mice, using an antihistamine drug that acts on hybrid dopamine receptors. It’s an innovative approach to HD therapeutics, but don’t start reaching for allergy meds ... Read more HD and Histamines: Targeting Hybrid Receptors to Quiet Stressful Brain Talk

Changing jobs: converting other cell types into neurons

Published date: 23 June, 2020

Researchers have known for quite some time that HD causes a progressive loss of neurons. But what if we could find a way to fill their place? In a new report, researchers used an intriguing strategy in living mice to do just that – they converted a different type of brain cell into neurons, with ... Read more Changing jobs: converting other cell types into neurons

HD Young Adult Study defines the sweet spot: symptom-free with measurable changes

Published date: 27 May, 2020

A new study headed up by Dr. Sarah Tabrizi, a pioneer in HD research, assessed pre-manifest HD young adults many years from predicted symptom onset with a battery of clinical tests. The goal of this study was to identify a sweet spot – a time when HD participants weren’t experiencing any observable symptoms, but when ... Read more HD Young Adult Study defines the sweet spot: symptom-free with measurable changes

Fountain of youth: HTT protein repairs neurons by maintaining youthful state

Published date: 13 May, 2020

A team of scientists has recently published their findings on how our bodies are able to repair brain and spinal cord injuries. They found that the huntingtin protein plays an important role in repairing damaged nerve cells. Repairing nervous system damage – the holy grail of medical science It has long been the ambition of ... Read more Fountain of youth: HTT protein repairs neurons by maintaining youthful state
Light and sleep

Light and Sleep

Published date: 7 April, 2020

Light & sleep Neurofilament Light Protein and Lifestyle Factors Commentary Words Dr Travis Cruickshank and Dr Danielle Bartlett

What does COVID-19 mean for Huntington’s disease families and HD research?

Published date: 6 April, 2020

COVID-19, short for coronavirus disease 2019, has taken the world by storm in almost every sense – many people have been infected with the SARS-CoV-2 virus, it’s created shopping pandemonium in stores, and many people are isolated at home. But behind that frenzied storm, scientists around the world have been working tirelessly to move research ... Read more What does COVID-19 mean for Huntington’s disease families and HD research?

Welcome to our new website!

Please bear with us while we iron out the last minute wrinkles! If you have any feedback about our new site, please fill out the form below.