DAY 2: CHDI Therapeutics Conference

The 15th Annual Huntington’s Disease (HD) Therapeutics Conference is currently taking place in Palm Springs. Here is a summary of the second day, put together by tweets from HDBuzz

By HDBuzz and Phylis Kitema | Photo: HDBuzz

Session: Path to prevention


Background: Enroll-HD, TRACK-HD & Self Enroll

Enroll-HD collects data from Huntington’s disease (HD) patients whether they have symptoms yet or not. All of this data is important for understanding how HD progresses as patients get older. It is important to note that people who participate in Enroll-HD don’t have to know their genetic status. Scientists can still get data to advance HD research while patient privacy is protected. 

Many researchers can use the data gathered from Enroll-HD to help guide future studies. This dataset will help advance HD research move forward in a quicker way. Enroll-HD is not the only big data project in HD.

TRACK-HD was another study which looked at changes in the brain structure over time in patients. Patient participation in these studies, helping scientists collect big data sets, is very valuable for HD research. There are lots of amazing trials going on right now collecting all sorts of data. 

A new and exciting initiative is Self Enroll. This would be a digital version of Enroll-HD where patients could provide data and updates without having to travel to an Enroll-HD site. Removing this barrier would hopefully encourage even more patients to participate.

Sarah Tabrizi

Sarah Tabrizi’s (University College London), talk is about her team’s research studying young HD adults. By studying HD in young adults, researchers can try to find the best time to treat HD.

You can read more about it here.

It has been known for a long time now that HD patient brains begin to change even long before they have symptoms which might be detected in the clinic. Again, these findings are known due to the huge datasets from TRACK-HD, PREDICT-HD, Enroll-HD and other studies.

In these studies, examining very early changes that occur, researchers are also focused on identifying biomarkers – molecules that can be used to judge disease progression – that will also help to determine if treatments are working. For all of the participants in the study lead by Tabrizi, the brain structure and function were extensively mapped resulting in a lot of important data. 

Along with detailed brain maps, Tabrizi is also collecting lots of data from CSF and blood to track the difference in these biomarkers over time and between patients with and without HD comparing between patients before and after symptoms become obvious. What they found in these extensive tests was that overall there are no differences between the participants with and without HD in the way that they think.

One of the biomarkers that was examined was neurofilament light (NfL) – a marker recently shown to increase as the disease progresses. They found that NfL levels are raised in HD patients very early, before they show any symptoms.

Very encouragingly, Tabrizi’s group finds that there aren’t differences in the way people with and without HD think even out to 24 years before they start to show symptoms. Measuring changes in the CSF levels of NfL could be a good biomarker for measuring how HD progresses in patients, even many years before they become symptomatic. This could help guide monitoring and treatment of patients in very early stages of the disease

Jianying Hu

Jianying Hu from IBM T. J. Watson Reserach Center, talk is about studying HD progression.Hu and IBM are working with CHDI to understand HD disease progression using lots of data collected from various studies.

Using these large datasets, Hu is gathering information not only on the HD population as a whole, but also for each individual patient to improve outcomes. This data can then be used by doctors to better treat HD patients. Because all of these studies collect different types of information there’s lots of different data for HD researchers to use.  Hu and colleagues use lots of cool cutting-edge computational methods to help build a model of HD progression with all of this data. Hu and her team are using data from all these HD clinical trials that has been collected over 4 decades. 

One of the ways this computational model could be used is to predict how symptoms might progress for HD patients, which could be helpful for clinicians to work out how best to treat and monitor patients. Using the computational model that they developed, Hu defined 9 different “disease states”, or stages of HD. To track progression, this model can be used to predict where the patient falls within these states.

This data is being used to drive discovery of therapies for HD specifically aimed at slowing progression. Their next steps focus on defining very early stages of the disease in more detail.

Steven McCarroll

Steven McCarroll from Harvard talks about his research into HD by doing single cell analysis experiments.  McCarroll’s work is focused on understanding what HD is doing at the cellular level – so identifying targets for therapeutics and biomarkers for progression. While people typically think of neurons when they think of cells in the brain, there are actually a variety of different cell types. For a disease like HD that affects every cell, it’s critical to understand how HD is affecting cells of the brain other than neurons.

Using advanced computational methods called machine learning, McCarroll’s group is able to sort out the different types of cells from the brain AND they made all of this cool software free for the community, there are over 25,000 downloads so far!

In fact, this software was able to find new types of cells in the brain. This is important as these new cell types were not consistently found in different species such as mice, but they are found in primates like monkeys.

Next, the McCarroll lab wanted to apply this technology to see if they could monitor HD progression and look for biomarkers of different stages of disease, by seeing which types of cells were found in patients early on and then later in the disease. It is been establishedfor a while that one of the most vulnerable cell types in HD are spiny projection neurons, or SPNs. With McCarroll’s single cell technology, he was able to show there were less and less SPNs as HD progresses. 

McCarrollgoes on to discuss biomarkers. Identifying new biomarkers for disease progression is critical not only to track HD over time, but also to definitively assess if therapeutics are having a beneficial effect.One of the biomarkers he’s exploring is mostly found in the SPNs. This means if this biomarker is tracked over time, it could correlate to loss of SPNs as HD progresses. This would be a great way for researchers to measure SPN loss without needing brain samples.