1800 244 735

Helpline (02) 9874 9777

Huntington's Disease Therapeutics Conference 2017 – Day 2

Day two of the conference looks at some of the most promising approaches to fighting Huntington’s disease.

Huntingtin lowering therapies

Exciting session planned for this morning, as the conference discusses “Huntingtin lowering” approaches to treating HD.

The first talk is from HDBuzz’s own Ed Wild (University College London), who is interested in developing “biomarkers” for HD trials. A biomarker is a lab test that can be done to track the progression of a disease, or the effect of a treatment. Good disease biomarkers for HD would track the progression of the disease more precisely than simply looking at clinical measurements like movement abnormalities. Tracking the progression of HD is complicated and we don’t have any reliable tests for measuring it in the lab, especially in blood samples. Wild’s group has been developing tests to measure cellular debris released by sick and dying brain cells. As brain cells get sick and die in brain diseases like HD, they release their contents into the cerebrospinal fluid. Some of these debris leak into the blood, where very sensitive new tools allow researchers to measure them. During the course of other brain diseases – like Alzheimer’s and Parkinson’s – brain cell debris levels rise in the blood. Wild’s team has discovered a marker in the blood, released from sick brain cells, that increases consistently as HD progresses. Increasingly severe HD mutations leads to higher levels of brain cell debris in the blood, as does aging. This is exciting – for the first time we can track the health of brain cells from blood samples alone

Next up, Harry Orr (U. Minnesota), who works primarily in a disease called spinocerebellar ataxia 1 (SCA1). Like HD, SCA1 is caused by the expansion of a repetitive stretch of DNA with the sequence “C-A-G”. In SCA1 this genetic stutter occurs in a gene called “Ataxin-1”, not the HD gene. We can learn a lot by comparing how the same type of mutation, when it occurs in different genes, causes brain cells to become sick. Orr’s lab has shown that reducing levels of the mutant gene which causes SCA1 improves symptoms in mice. For many years, Orr’s lab has been using mouse models of SCA1 to try and discover interventions to slow disease. Orr’s lab is using antisense oligonucleotides (ASOs) to reduce levels of Ataxin-1 in the brain, similar to approaches being taken in HD. Comparing results between SCA1 and HD could help understand both diseases better.

Nicole Deglon (Lausanne U.) has worked for many years on huntingtin lowering approaches to HD therapy. She has a special interest in using engineered viruses to deliver huntingtin lowering tools into brain cells. New “gene editing” tools, including one called CRISPR/Cas9, allow researchers to modify DNA in adult cells. Deglon’s team has developed several gene editing tools designed to reduce levels of the HD gene. Using her viruses, Deglon is able to deliver these gene editing tools into the brains of HD mice, where they work very efficiently. One concern about gene editing tools is that the “scissors” that cut the DNA stick around forever, long after they’re needed. Deglon’s team has developed a very cool new trick to turn off the DNA scissors after they inactivate the HD gene. This is an exciting advance – it seems likely to make gene editing in the brain safer in the long-term. Her group has evidence that inactivating gene editing tools leads to less unintended cuts in DNA.

The final speaker in this morning’s huntingtin lowering discussion is Liz Doherty from the CHDI Foundation. The foundation is pursuing a wide range of huntingtin lowering technologies Doherty describes the foundation’s search for a “small molecule” that will lower huntingtin levels. Unlike ASOs or the gene editing tools that Deglon described, a small molecule is a drug that could be taken as a pill. This would be a better way to take medicine, but so far no one has ever identified a small molecule which lowers huntingtin levels. Now CHDI is conducting an exhaustive search of over 130,000 different chemicals, hoping one of them will result in huntingtin lowering. In the first round of searching, they’ve identified 4 different chemicals that result in really robust huntingtin lowering in cells. Important to develop new ways to achieve huntingtin lowering, in case any unexpected concerns arise with other approaches like ASOs. So exciting to see the huge diversity of approaches to achieve huntingtin lowering at different stages of development.

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

Latest Research Articles

Updates from the EHDN Plenary Meeting 2020

Published date: 8 January, 2021

In September, the European Huntington’s Disease Network (EHDN) hosted a virtual webinar event which comprised presentations on some of the latest scientific research as well as clinical studies of Huntington’s disease (HD). Researchers, doctors, patients and other interested folks, tuned in for an afternoon of talks as well as question and answer sessions to learn ... Read more

Uncovering the dark side of DNA repair to design HD treatments

Published date: 22 December, 2020

A gene known as ‘MSH3’, which encodes a protein involved in fixing and maintaining our DNA, has become a hot topic in Huntington’s research since being implicated as a key driver of the disease by multiple genetic studies. In a recent publication, a team of scientists from the National University of Ireland, Galway, have provided ... Read more

Huntington Study Group (HSG) 2020 Annual Conference: HD in Focus – Day 2

Published date: 1 November, 2020

The second day of the HSG conference was another busy day of presentations from HD researchers and clinicians. The day kicked off with a talk from Vaccinex who gave us an overview of their work on the SIGNAL clinical trial. Unfortunately, pepinemab, the medicine tested in this trial, did not influence HD symptoms and the ... Read more

Huntington Study Group (HSG) 2020 Annual Conference: HD in Focus – Day 1

Published date: 30 October, 2020

The Huntington Study Group (HSG) is a clinical research network focused exclusively on HD. Yesterday the HSG annual conference began with a schedule jam-packed with virtual talks from researchers, clinicians and different companies who are all working towards finding new medicines for HD. The day encompassed many interesting presentations which covered a lot of the ... Read more

Treatment for neurological disorder could be repurposed for Huntington’s disease patients

Published date: 22 October, 2020

While developing a drug called branaplam for patients with SMA, the pharmaceutical company Novartis discovered that it could hold promise for people with HD. The FDA has granted a special status called Orphan Drug Designation to branaplam. An existing drug…for huntingtin lowering? The pharmaceutical company Novartis has announced that the U.S. Food and Drug Administration ... Read more

Sad news from the SIGNAL study: pepinemab does not influence HD symptoms

Published date: 23 September, 2020

The SIGNAL clinical trial was designed to test a drug called pepinemab in people with early Huntington’s disease. The key results of that trial were recently announced, and unfortunately, pepinemab did not slow or improve HD symptoms as hoped. What was the SIGNAL trial, and who participated? The SIGNAL trial was launched in 2015 by ... Read more

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.