Our final report from the Annual Huntington’s Disease Therapeutics Conference.

Thursday morning: Lessons from clinical research

09:06 - This morning’s sessions are focused on findings in people with HD, rather than animal models or cells. Important stuff!

09:09 - Gil Di Paolo is interested in what scientists call “lipids” and most people call “fats” in the brain. Our brains are about 60% fat.

09:11 - Brain fats come in a bewildering array of types, some abundant and some quite rare. Even rare fat types play important roles in the brain.

09:13 - Di Paolo reminds the audience that the huntingtin protein likes to stick to “membranes”, the fatty sheets that form cell boundaries

09:13 - Also, production of fats is slowed in the HD brain, which could result in changes in the levels of various fats in the brain.

09:15 - Di Paolo’s lab specializes is “lipidomics”, or the accurate measurement of hundreds (or even thousands!) of different fatty molecules

09:16 - Di Paolo has been working with HD brains to see if it’s true that there are reductions in the amounts of important fats.

09:18 - Di Paolo is also studying the fatty molecules found in the blood of HD mutation carriers from the TRACK-HD study

09:24 - Each tissue has a unique fat signature - the brain is very different than the blood in terms of what fats are present

09:28 - Di Paolo observes a number of very specific fat changes in the blood of people carrying the HD mutation

09:30 - These changes are distinct from changes seen in Parkinsons disease, suggesting something specific might be going on in HD

09:36 - Di Paolo just for these results 5 days ago, so watch this space for more a more detailed analysis of this exciting new results.

09:40 - Disclaimer: the next guy up is some dude named Dr Ed Wild, so beware our objectivity might be slightly compromised!

09:49 - Wild is working to isolate cerebrospinal fluid from HD mutation carriers, an important way of seeing what’s going on in the brain

09:53 - Why is spinal fluid important? We want to learn about brains, but can’t sample brain tissue safely. Sampling spinal fluid is much safer.

09:56 - Other diseases, like Alzheimers, have well characterized spinal fluid markers to track disease progression, but HD doesn’t

09:58 - Wild has used a fancy machine that lets him measure tiny amounts of the huntingtin protein in spinal fluid

1000 - Interestingly, the amount of huntingtin protein in the spinal fluid rises with HD progression, and correlates with HD symptoms

1002 - The spinal fluid seems special - blood levels of the huntingtin protein don’t show the same interesting pattern.

1006 - Wild is also using his spinal fluid to investigate ideas scientists have proposed, measuring levels of specific chemicals in spinal fluid

1010 - Wild’s collection of spinal fluid is an important resource to provide a window into the HD brain

1012 - Wild is also interested in the flow of spinal fluid throughout the brain - he’s launching an imaging study to investigate this

1014 - Wild also announced the launch of his ‘HDClarity’ consortium, which will collect high quality spinal fluid at a number of centers worldwide

1023 - Guillermo Cecchi, of IBM research, addresses the conference on his teams use of computational techniques in biology and medicine

1024 - In particular, he’s studying whether computer analysis of speech can be used to help in psychiatry. Could Siri replace your therapist?

1049 - Awesome to see next generation computer technology and being used to help understand Huntington’s disease

11:23 - Diane Stephenson of the Critical Path Institute addresses the conference - her organization works to speed development of therapies.

11:25 - The goal of the Critical Path Outcome is to bring together groups involved in developing drugs - companies, patients and government agencies

11:29 - They try to fill gaps in the drug development process to speed the process of getting drugs approved.

11:30 - A major goal is to get scientists, companies and other stakeholders to share their data from clinical trials

“There’s a lot of excitement around the upcoming trial of Isis Pharmaceuticals’ trial of a ‘gene silencing’ drug. But we must remember it focuses primarily on safety ”

11:32 - More on the Critical Path Institute here: http://c-path.org/

11:36 - A major problem that exists in drug development is that a large amount of data about patients and drugs is spread across many databases

11:37 - The CPI has been developing techniques to standardize all this data and put it together so everyone can work with standard databases

11:38 - These databases about drug effects and disease progression can help drug companies plan better clinical trials in the future

11:40 - With all this data collected, it’s possible to actually simulate a clinical trial before you run it - asking ‘what-if’ types of questions

11:42 - These computer simulations let people planning trials game out the best way to run efficient trials ahead of time

11:57 - Michal Geva of Teva Pharmaceuticals @tevapharm offers an update on Teva’s Huntington’s disease drug programs

11:57 - In an unprecedented show of confidence in the HD community, Teva has not one but two drugs in clinical trials for Huntington’s disease

11:58 - The first drug is pridopidine, also known as Huntexil. This is aimed at improving movement symptoms in HD http://en.hdbuzz.net/025

12:00 - Teva hopes that their Pride-HD study will provide the evidence needed to get Huntexil licensed for HD patients http://www.huntington-study-group.org/CurrentClinicalTrials/PrideHD/tabid/305/Default.aspx

12:02 - Day 2 of updates from the annual HD Therapeutics Conference in Palm Springs http://en.hdbuzz.net/190

12:08 - While Pride-HD is happening, Teva’s scientists have shown some interesting things about the drug…

12:08 - … including a hint that it could help with the connections between brain cells

12:15 - Teva lso found pridopidine may increase a chemical called BDNF, which protects brain cells. This may not happen in people though!

12:17 - Teva’s second drug is laquinimod, which is being tested in another Huntington’s disease trial - LEGATO-HD. http://www.huntington-study-group.org/CurrentClinicalTrials/LEGATOHD/tabid/317/Default.aspx

12:18 - Laquinimod aims to alter the behaviour of the brain’s immune cells - called microglia. They’re overactive in HD and may be doing harm

12:19 - So Teva hopes that damping down the activity of microglia might help brain cells to survive in HD, or even slow progression.

Thursday afternoon: Clinical trial updates

14:11 - Sarah Tabrizi and Sarah Gregory, UCL, address the conference on the findings of the “TRACKOn-HD” study

14:12 - TRACKOn is designed to follow up the findings of the TRACK-HD observational study, which found a number of changes in HD mutation carriers

14:16 - Interestingly, in the TRACK-HD study found a number of brain imaging changes that weren’t associated with changes in thinking ability.

14:19 - So, how can the brain shrink without causing problems in thinking ability? Tabrizi is interested in how HD brains ‘compensate’ during HD.

14:20 - Brain imaging from the TRACKOn-HD study is being used to understand how communication between brain regions is altered in HD.

14:23 - There seems to be much less communications between distant brain regions in HD, and more short range communication

14:27 - Tabrizi’s team is interested in designing experiments that let them study how brains undergoing damage are coping.

14:33 - They’ve been able to find patterns of brain activity that are higher in HD mutation carriers doing better on thinking tasks

14:35 - This suggests that brains do have some ability to cope with ongoing damage in HD, at least in some people.

14:36 - But, who cares, can this kind of information help people with HD?

14:37 - Tabrizi is interested in whether people can be trained to use these compensation techniques.

14:38 - Her group has done a “neurofeedback” study in HD patients, putting them in an MRI machine and training them to modify their brain activity

14:39 - This training led to specific patterns of brain activity, and improved performance on a simple movement task.

14:42 - Tabrizi suggests that this kind of neurofeedback study isn’t a treatment for HD, but more like “physical therapy for the brain”.

14:53 - Marios Politis from King’s College London uses a brain scan technique called PET scanning to study the brain in HD

14:54 - PET uses injections of chemicals called ‘tracers’ to look at changes in specific cell types in the brain.

14:55 - For example, one tracer shows changes in cells that use the signalling molecule dopamine, while another shows the activation of immune cells

15:08 - Politis: PET is a powerful tool but so many different methods have been used in the past, it’s difficult to be sure what’s going on in HD

15:11 - Politis announces PETMARK-HD, a CHDI-supported study of PET imaging that aims to overcome these issues

15:19 - Politis illustrates the different chemical brain systems that will be looked at in PETMARK-HD http://t.co/mghXgruyAb

15:23 - Politis will also use PET to study the overlapping brain networks that are involved in HD

16:02 - Ray Dorsey of University of Rochester and the Huntington Study Group gives an overview of previous clinical trials in HD

16:08 - Dorsey: 2014 was remarkable for the early halting of 2 huge trials for lack of benefit http://hdbuzz.net/181 http://en.hdbuzz.net/171

16:09 - However, several trials have shown new possible treatments to be at least safe and well tolerated this year, and many more trials planned

16:13 - The Huntington Study Group publishes HD Insights which regularly offers updates on clinical trials in HD http://hdinsights.org

16:17 - The next generation of trials, starting now and soon, will be of drugs specifically aimed at known problems in Huntington’s disease

16:37 - Finally Prof Bernhard Landwehrmeyer closes up with a look ahead to forthcoming clinical trials

16:38 - Landwehrmeyer: we are now testing drugs designed specifically for HD

16:40 - Future trials will also be strengthened by the use of biomarkers to give clearer ideas of what works and what doesn’t

16:44 - There’s a lot of excitement around the forthcoming trial of Isis Pharmaceuticals’ trial of a huntingtin lowering / gene silencing drug

16:44 - But we must remember the trial focuses primarily on safety

16:49 - Landwehrmeyer: people who don’t take part in the first gene silencing trial aren’t missing the boat

16:50 - If the drug proves safe, future trials will be bigger, and there’ll be other new drugs too

16:57 - The Amaryllis trial is studying a drug aimed at improving brain signalling by reducing tha activity of an enzyme called PDE10A

16:59 - More on the Amaryllis trial here: http://www.hdsa.org/research/clinical-trials-1/pfizer-pde10a-inhibitor.html

01:04 - In Europe, a trial of deep brain stimulation - giving small electrical shocks to targeted brain areas - is planned to start in 2015

01:05 - Hopefully DBS will provide an additional treatment option for movement problems that don’t respond to current drugs

01:08 - In summary: trials are happening - all HD family members should think about taking part so we can get these treatments tested ASAP!

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