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EuroBuzz 2014: day three

Our final report from the European HD Network meeting. For the first time, video of many presentations, including our ‘EuroBuzz’ sessions will be made available online shortly.

08:09 – This mornings EHDN session focuses on one of the most exciting therapeutic options of all – Huntingtin lowering

08:10 – Leslie Thompson is interested in how small changes to the huntingtin protein itself control it’s turnover. If we can understand how cells normally get rid of huntingtin, maybe we can increase the process with drugs. Thompson’s team is exploring a key pathway that cells use to get rid of huntingtin called “sumo-ylation” (really!). Another way to benefit cells with the HD mutation is to help them make proteins more carefully. Cells make proteins to do most of their work, which have to fold into complex shapes, this process can sometimes go wrong. A normal part of the cell protein-folding machinery is called TRIC. Giving cells more TRIC protects them from the HD mutation. Thompson is now exploring different ways to get TRIC into the brain, to understand whether this could be a therapeutic option for HD.

08:27 – Doug Macdonald of the CHDI foundation has been working for a long time on Huntingtin lowering therapeutics. Huntingtin lowering is one of the most exciting potential therapies for HD. The mutant HD gene gets used by the cell to make a copy we call a “message RNA”, which gets turned into a protein. Confused? Surprisingly, there are now therapies that can attack each of these levels – gene, message and protein, to try and get rid of it. So which approach will work best to reduce the symptoms of HD? CHDI is, with other investigators, trying a number of approaches. One issue with all these approaches is how will we know if we’ve reduced huntingtin levels? Amazing new approaches allow researchers to count individual copies of the huntingtin protein. Because they’re so sensitive, these techniques let scientists measure huntingtin in cerebrospinal fluid, which bathes the brain. If we can get drugs into the brain to lower HTT, maybe we’ll be able to ensure it’s working by collecting spinal fluid. Donating spinal fluid is not trivial, but it’s a lot easier than donating your brain! CHDI is working to develop high tech measures of brain function that work in HD mice, in hopes they’ll also work in people.

08:51 – Jang-Ho Cha, of Merck and the HDSA, addresses the conference on the challenge of clinical trials in HD. “Our finish line: Treatments for HD. What are we going to require to get to this point?” Without a path through clinical trials, we won’t get effective treatments. There’s two kinds of research we need to get to clinical trials – “clinical” work in people, and “pre-clinical” work in the lab. Along the way, there’ll be impossible seeming gaps, but if we’re clever we’ll get across. Once we figure out how to solve impossible seeming problems for one trial, the solutions will help speed future ones. The first phase of testing a drug is a ‘phase 1’ trial. These trials are just to establish a drug is safe and well-tolerated. Biomarkers, measurable traits that can be measured in people, help keep HD drug developers ‘on the trail’. Drug development for multiple sclerosis was accelerated by the development of MRI-based biomarkers. This rapid speeding of trials in MS has led to 14 treatments for this previously untreatable disease. What is ‘phase 2’ study? A study designed to provide some “proof of concept” that a drug works. We have to think differently about drugs designed to improve HD symptoms and those we think might actually prevent the disease. Better ways of quantifying HD symptoms will lead to smaller, faster and cheaper trials. A ‘phase 3’ trial is designed to provide ‘pivotal’ evidence that a drug works, and can lead to its approval. “No patients, no trials”. An engaged and informed HD community is required to complete the clinical trials we need.

10:10 – Prof Landwehrmeyer’s thoughts on coping with disappointment and frustration, quoting Churchill – “The route to success is to go from failure to failure with undiminished enthusiasm”

10:22 – Landwehrmeyer tells us: We’ve been saying “The drugs are coming” for years – it’s finally happening

Latest Research Articles

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

Serious side effects reported for some people treated with the huntingtin-lowering drug AMT-130, currently in clinical trials

Published date: 29 August, 2022

Last month, we relayed positive news from uniQure’s trial testing AMT-130, a gene therapy delivered via brain surgery to lower huntingtin (HTT). Data released by uniQure in June suggested AMT-130 was safe and well tolerated in the small group of people that were treated with a low dose of the drug. Now we’re back to ... Read more