1800 244 735

Helpline (02) 9874 9777

Huntington's disease therapeutics conference 2019 – Day 2

Jeff and Ed report from the Huntington’s Disease Therapeutics Conference – the biggest annual gathering of HD researchers. This year’s conference is bigger and more exciting than ever.

Read about Day 1 here.

Advanced tools for translational research

Morning everyone! The second day of the 2019 HD Therapeutics Conference is kicking off in Palm Springs. The first session is “advanced tools for translational research”.

The first speaker today is Lauren Byrne from UCL who studies biomarkers in blood and cerebrospinal fluid. Byrne measured mutant Huntingtin in CSF, and neurofilament light protein in CSF and blood in 80 volunteers. Neurofilament light or NFL is a protein found in neurons and released when they are damaged. Byrne also did MRI scans to see how each biomarker predicts brain shrinkage. Surprisingly, neurofilament turns out to be a better predictor the mHTT of clinical symptoms and brain volume. Changes in these “biofluid” markers were among the earliest detectable changes too, preceding imaging and clinical measures in the sequence of events in HD.

Byrne has now completed the 2-year follow ups from the HD-CSF study and shows that the NFL seems to be changing as expected over time, and can be measured using a new system that tests 4 molecules at once.

Next up is Amber Southwell, from UCF, who is also interested in developing tools to quantify mutant huntingtin in the spinal fluid. Southwell’s team was the first to show that when mice are treated with a Huntingtin lowering therapy – specifically an ASO from Ionis Pharma – levels of mutant Huntingtin in the spinal fluid are reduced. This is important – it means that when we treat human HD patients with Huntingtin lowering drugs, we’d predict that the levels of mutant Huntingtin in the spinal fluid will go down. This is one of the things reserarchers mean when they say a measurement is a “biomarker”.

Southwell’s team is doing a cool series of experiments with mice that have no Huntingtin in specific types of brain cells. This is enabling them to map the exact type of brain cell responsible for releasing mutant Huntingtin into the spinal fluid.They’re also conducing another set of experiments focused on understanding the exact process by which mutant Huntingtin makes its way from brain cells called neurons into the spinal fluid. One process of brain bathing called “glymphatic clearance” seems likely to play a role in mutant Huntingtin making it’s way into the spinal fluid.

Next is David Salzman of sRNAlytics, a company that investigates the use of RNA to study diseases.RNA is the single-stranded cousin of DNA. Cells use RNA for many functions, most famously as the “working copy” of genes they want to switch on. That’s called messenger RNA. Less famously, cells produce many small RNA molecules that help in the regulation of gene switching. They have names like microRNA and there are lots of different ones.We understand genes as recipes for proteins pretty well, but micro RNAs are much morel mysterious at the moment.

SRNAlytics identifies patterns of small RNA changes and uses artificial intelligence algorithms to identify what part of the body they come from, and how they change in different diseases. A panel of 60 small RNAs in CSF can apparently distinguish between Huntington’s, Alzheimer’s and Parkinson’s with decent accuracy. Two small RNAs are of particular interest in HD, but it’s important to understand exactly what they do in healthy and HD brains in order to figure out their value as possible biomarkers.

New animal models

Guoping Feng, from MIT, is up next. His lab is working on developing new primate models of HD. He says mice are very useful, but they don’t have all the same brain regions as humans, so we need to study more sophisticated brains as well. It used to be difficult to impossible to genetically modify primates, like monkeys, but new genome engineering tools make it possible. Tools like CRISPR/Cas9 allow precise DNA edits to be made to the DNA of monkey embryos. Feng’s lab is one of the world’s best at making changes to primate DNA. He describes that they’ve learned from human IVF clinics the best ways to keep primate embryos healthy. Feng’s lab has generated a novel monkey model of a genetic form of autism. These monkeys have very interesting behaviors that really resemble humans with Autism, including altered social behaviors. They are now working to develop a monkey model of Huntington’s Disease, and have conducted initial experiments suggesting it should be possible.

Hideyuki Okano, of Keio University, also works on primate models of human diseases – specifically Marmosets. His lab has genetically modified Marmosets to have a form of Parkinson’s Disease caused by a genetic mutation. These animals have symptoms very close to those observed in Parkinson’s Disease patients, including a very challenging sleep condition called REM sleep behavior disorder (RBD). They also have tremors and walking problems that resemble Parkinson’s Disease patients. It’s a good argument for using more more sophisticated animals to model progressive brain diseases. Okano’s lab is now developing techniques to generate similar models for Huntington’s Disease.

Thats all for today! Be sure to check out our write up of day 1 here and stand by for our final roundup tomorrow.

Latest Research Articles

Forward momentum for Roche and Wave in latest news about huntingtin-lowering trials

Published date: 30 September, 2022

In the past week or so, during and following a big HD research conference, two companies developing medicines for Huntington’s disease announced news about their huntingtin-lowering drugs. First, the pharmaceutical company Roche announced plans for a new clinical trial of tominersen. Then, the genetic medicines company Wave Life Sciences shared early data showing that its ... Read more

Focusing in on fibrils; scientists give us a glimpse of huntingtin protein clumps

Published date: 8 September, 2022

A group of scientists from the EPFL in Lausanne, Switzerland have published a paper in the Journal of the American Chemical Society, describing clumps made up of a fragment of the huntingtin protein. A word that’s commonly used to describe these is “aggregates.” Using very powerful microscopes, the team was able to zoom in and ... Read more

Hereditary Disease Foundation (HDF) conference 2022 – Day 4

Published date: 2 September, 2022

DNA repair and CAG repeat instability The effect of HTT lowering on CAG repeat expansions Welcome to last day of the @hdfcures conference! We’ll only be sharing a few talks from today’s sessions, which focus on DNA repair. The first is from HDBuzz’s very own Jeff Carroll! Jeff will be sharing his work on HTT ... Read more

Hereditary Disease Foundation (HDF) conference 2022 – Day 3

Published date: 1 September, 2022

Pre-clinical work moving toward trials New tools to lower HTT showing promise in animal models Welcome back! The first talk we will be tweeting about today is from Anastasia Khvorova, who will be telling us about her teams work on lowering of Huntingtin using technology called RNAi. One of the problems in studying drug delivery ... Read more

Hereditary Disease Foundation (HDF) conference 2022 – Day 2

Published date: 31 August, 2022

We’re back for day 2 at @hdfcures! This morning’s talks will be focused on clinical trial planning and therapeutic updates from clinical studies. The sheer number of talks related to human trials compared to previous years is so encouraging! Updating metrics for clinical trials A better system for disease categorization The first talk of this ... Read more

Hereditary Disease Foundation (HDF) conference 2022 – Day 1

Published date: 31 August, 2022

Hello and welcome from the HDBuzz team who are currently at the Hereditary Disease Foundation (@hdfcures) 2022 Milton Wexler Biennial Symposium in Boston! It’s the dawn of an exciting new era for HDBuzz. Due to our new partnership with @hdfcures, we are now able to live tweet many of the talks from this meeting which ... Read more