In a question and answer session coordinated by the HD Association of the United Kingdom, Dr. Ed Wild answers questions about the recently announced trial
By Dr. Ed Wild on December 18, 2017 Edited by Dr. Jeff Carroll
The research news, announced on December 11, 2017, that a research team from the Huntington's Disease Center at University College London have taken a significant step towards a possible treatment for Huntington's disease, raised many questions for the Huntington's disease community. Dr. Ed Wild answered some of these questions on behalf of the HD Association of the United Kingdom, helping to contextualize the meaning of this news for people affected by Huntington's now and in the future.
Thanks for all your fantastic questions. It is a testament to the dedication and determination of this community that there were so many detailed and thoughtful questions. I have answered the best I can. W Although I am involved in the HTTRx program as a consultant and researcher, I am not speaking on behalf of Ionis, Roche or UCL here, but as a co-founder of HDBuzz and a scientific advisor to the HDA. None of my answers should be interpreted as medical advice. I hope you find them useful!
Could this modern medicine cure someone who already has Huntington's? I am aware that it will reduce the HD protein, but for those who already suffer without medication, has the damage already been done? Or could protein removal help?
Will this help someone who has HD or only new sufferers?
First things first: the news that IONIS-HTTRx decreases the mutant huntingtin protein is excellent, but it is not a cure. In general, I think it is better to wait for an "effective treatment" because a cure is a bar VERY high to clarify. We can not cure HIV or diabetes, but medical advances have dramatically transformed them into manageable conditions. Progress occurs gradually, and we have to be in this for the long term.
That said, we believe that reducing the level of mutant protein huntingtin with IONIS-HTTRx has the potential to make a positive difference, even after HD symptoms have begun. But we will not know until a larger and longer test has been run. In the test that just ended, people only received treatment for 3 months, which is too short a time to give an idea of whether the drug slows the progression of HD.
In the course of HD there are some neurons that have been lost, and others that are alive but sick. We can not replace lost neurons but we hope that the medication will allow patients to function better.
The earlier we try, the more likely we are to see the benefit. Unfortunately, even if we see a slowdown or improvement in early HD, there is likely to be a point later in the disease where the drug does not produce significant benefits. Again, this is something that we can only discover by testing it on more people for longer periods.
What are the next steps to use this treatment to make it available to other patients who are willing to try it as soon as possible? How and when?
Will it be tested now on a larger group of people? And if so, when is that planned?
The next step is a longer and larger trial to evaluate the "efficacy of the drug ": does it slow the progression of HD? That trial is now being planned and we expect an announcement from Roche in the coming months. If you have HD or are at risk, I have three tips:
1) Be sure to follow up regularly at an HD clinic that has a research interest, either directly or at a site that can provide volunteers for others clinical trial sites .
2) Enroll in the ENROLL-HD study (details on enroll-hd.org). That study is used as a recruiting database for clinical trials and is the first place where teams will be seen once recruitment begins.
3) Take care of yourself. The next test may take more than a year, and the healthier you are, the more likely you are to be in the next test. Keep up with visits to the clinic, visits to the general practitioner, visits to the psychiatrist, physiotherapy, speech and language therapy. Stay active, exercise and eat well. Seek advice early if your HD gets worse or if a new medical problem arises. Sign up to receive HDBuzz email alerts: hdbuzz.net.
When do you think the medication will be available to people who tested positive or show symptoms?
What is the criterion? to be part of the trial, and how many patients will be in the new admission?
My best guess is that the next big trial will start at the end of 2018 or the beginning of 2019. That sounds very far away but organizing a test with perhaps dozens of sites and hundreds of patients is a huge thing to organize. Roche, Ionis and academic researchers are working as quickly as possible to get the next planned steps.
I think we can expect the test to last around 3-4 years. Again, that sounds like a long time, but that is the time it will take to give the medication the best chance to prove it works. The worst case scenario would be to accelerate the next trial and obtain a negative result because the trial was too short.
On the other hand, if the medication is better than we expected, the trial could be shorter.
If the result is good, Roche will request a license to prescribe it, which could take the total time of 5 to 6 years or even more if there are problems along the way. It's worth being honest here and confessing that scientists generally underestimate how long these things have been. I'm sorry if it takes longer than the assumptions I've given here. If it does, it will not be because we are not trying 100%.
Finally, it is worth noting that the test may show that the medication does not work, that it does not slow down the progression of HD. That would be bad news, and we would have to find out why it happened and see what we can do about it, but it would not eliminate the fact that the gene and protein are the best target to fight HD.  Curious about effectiveness in JHD .
The current trial had a minimum age of 25 years, so no JHD patients were enrolled. The same protein is responsible for JHD so if the drug works for late-onset HD, it should also work on JHD . However, JHD is a more aggressive form of the disease, and the brains of young people might be more sensitive to side effects, so it could be harder to treat, even if the medication works well . I can promise you that finding the answers to these questions and helping people with JHD is a priority for everyone involved.
Do the patients who participated in the trial continue with the treatment?
Yes. The 46 volunteers of the test that has just finished will be invited to participate in an open label extension study or OLE. All OLE participants will receive the active drug regularly: none will be given a placebo . There are three reasons for this.
1) Thank you for taking the risk of being among the first humans to receive this medication. Everyone involved in HD research is a hero who helps change the world, but these 46 have perhaps taken the greatest personal risk on behalf of our community.
2) To obtain more data, as soon as possible, about more time, long-term safety of the drug.
3) Because people generally can not be in 2 different stages of the same program, so these 46 people probably would not be able to participate in the next testing phase.
" The next step is a longer and larger trial to evaluate the" efficacy "of the drug: does it slow down the progression of HD?
I think a lot of people do not get tested because up until now there is not much to do if you have a positive result. If you choose not to get tested before you start this, will it affect how quickly you test? Can you get the treatment?
Getting tested is an intensely personal decision and I would not like to convince anyone in any way.It is something that should be considered taking into account all the pros and cons, in a conversation with your loved ones and your genetic counselor
The next big trial will almost certainly involve people who have signs and symptoms of HD, and who have had a positive genetic test, but after that, it is very possible that they will investigate People with a positive genetic test result and still have no symptoms, to see if it prevents the disease.It is probable that people need to know their genetic status to participate in that prevention test. I do not know how far the trial is, because it depends a lot on how the next essay goes.
This week's announcement is no reason to get tested . When prevention tests are announced, and if tests are required before you can participate, there will still be time to get advice and get tested if that is what you want to do.
On the positive side, there is one thing you can do now, to help with HD research and get your name on the list of people interested in future trials, even if you have NOT been tested. It is to sign up for Enroll-HD (http://enroll-hd.org). HD family members at risk and not evaluated can participate.
At what stage of disease progression can the medication be administered? that is, can it be administered before the symptoms appear, therefore, it acts more as a preventive measure? As I understand (correct me if I misunderstood), as the protein accumulates in the brain, the symptoms progress: will the drug be effective if there is no accumulation present?
We hope the following The trial is in people with early HD, but work is already under way to think about trials to assess whether they can prevent onset in people without symptoms. That is definitely the goal. We do not know how early it might be effective or it might be necessary to take it, but I think we may be able to use the concentration of proteins in the spinal fluid and other measures (biomarkers) in the future to guide the treatments. But first, everything must be examined in clinical trials.
I understand that this trial has established the safety of the medication and an initial indication that it can be effective. Will the next stage look at persistence within the body to begin to see what kind of drug regimen may be necessary? For example, a lumbar puncture once a year to inject the drug is probably acceptable, one weekly probably not!
Everyone involved wants to devise a regimen that is effective but has the least possible lumbar punctures I hope different options are tried in future trials, but we still do not know what those options might be.
I am interested in knowing what the next stages of clinical trials are, and provided they are validated at each stage. What are the optimistic and conservative estimates of when the treatment would be in the market? Also, will it be available before in Extended Access / Compassionate Use?
IF HTTRx REALLY slows the progression of HD, I think that in order to prescribe the medication through the NHS, my optimistic estimate would be 5-6 years, very conservative estimate 10-12 years. Others could give you more or less optimistic numbers! And if we get a negative or disappointing test result throughout the process, things could change drastically.
But remember: HTTRx is not the only drug in development for HD, it is simply the one that excites us the most. There are many ways to achieve the goal of reducing mutant huntingtin, which is expected to start new trials soon or already in initial trials. In addition, there are other drugs that are developed and tested with the aim of slowing down or preventing HD in other ways, by helping to restore normal brain function in the presence of the mutant huntingtin protein .