"Diagnose and adios" ("adios" is the Spanish word for goodbye) is the description for Huntington's disease used by a prominant neurologist in a Medscape interview following the American Academy of Neurology (AAN) presentation of IONIS huntingtin protein lowering clinical trial.  The neurologist is the highly respected chairperson of the AAN scientific committee that chos at this prestigious conference.  In this interview she said it was exciting to have breakthroughs in Huntington’s because it is almost a “diagnose and adios" disease. In this same interview that was e-blasted to thousands of doctors, she went on to say that depression in HD is untreatable, This is simply untrue. Many neuropsychiatric symptoms of HD, including depression, are very definitely treatable.  Even at the top, there is lack of knowledge about what is treatable in HD. 


The Research-Medical Care Disconnect:  Further comments during the Medscape interview: Although it's still early days, she said the IONIS trial was chosen as one of the top studies presented because there have been so few options for patients with HD. "Having breakthroughs in this area is exciting to me as a neurologist.  Any time you look someone in the eye and they say 'Help me,' but you have nothing to offer, obviously there are some problems."


The HD community is grateful to this doctor and the committee that chose to feature the hopeful IONIS trials results. And no doubt this doctor meant no harm for HD families.  However, her "diagnose and adios" and "untreatable depression" description e-blasted out to thousands of general physicians about HD is both incorrect and disheartening.  Though this doctor is not an HD expert, she works at Massachusets General Hospital, a leading teaching hospital where there is a large HD Center of Excellence.  Even at this top-ranked hospital, non HD neurologists appear to be unaware that neurospychiatric symptoms in HD are treatable.


Why the lack of knowledge of HD Care? While we indeed don’t yet have a drug to slow down disease progression, HD experts believe we certainly do have drugs and other therapies that can treat depression and most other neuropsychiatric symptom complications. Unfortunately doctors are not taught about these treatments.  I believe this is because HD physician organizations and teaching hospitals focus on research, and provide relatively little professional education on medical care and optimal treatment of those with symptom complications in HD.  When doctors are not taught about treating HD, our HD families are the ones who suffer.

What can be done to improve HD Care Education for physicians and other medical providers? Though the Huntington Study Group provides medical education during their annual meetings and on their website, this reaches very few front-line medical care providers.  Similarly while the Huntington's Disease Society of America has published their Physicians Guide to Care in HD, few medical providers know how or where to access it.  


How can guidelines improve medical care?  Education about medial care can be provided in guidelines. Another proven way to improve care in many diseases is to have treatment guidelines. Experts use clinical trial evidence and expert experience to make best recommendations for in medical practice.  Guides are then published in medical journals that can easily be accessed by medical providers using web sites such as PubMed. When followed, guidelines have been central to improving the quality of care whether provided by specialists or generalists.


Though there is little evidence to inform best care in HD,  experts have developed guidelines for several neuropsychiatric complications and choreas based on their experience. These experts believe that neuropsychiatric and chorea symptom complications in HD are treatable. 

Three treatment guides have been available since 2011 for treatment of chorea (which is in need of an update), and for two neuropsychiatric symptoms including irritability and obsessive-compulsive behaviors.  These guides are posted on the Huntington Study Group site and at HDDW, WeHaveAFace and Help4HD.  Guides based on expert opinion for five more symptoms including agitation, anxiety, apathy, psychosis and sleep disorders will be published in the Journal for Huntington's Disease within the next several months. Summaries of both will be published on HDDW and offered to others.

Guidelines aren't helpful if no one knows about them.  At least so far, peer reviewed guidelines for HD that have been developed by working groups of both HSG and EHDN have not been endorsed or disseminated by either organization. By contrast, for other diseases, guidelines are promoted at conferences, and are more likely to be followed by general physicians when specialty organizations actively support them (the top-down approach).  Until then the "untreatable" designation is likely to persist among medical systems.  

The best alternative approach for families is the  "down-top" of bringing the guideline information to their medical providers who lack knowledge of HD care.






The press release from Roche and IONIS announcing a correlation between lowering mutant huntingtin protein and improvement in clinical measures of Huntington disease (HD) was exciting news. And it was also important for the HD community when it was featured at the American Academy of Neurology (AAN) last week.  The community felt the thrill.  However after the brief ride up the roller coaster, the reality is that we probably can't draw any useful conclusions about this report of clinical benefit.  Hard to know if it represents a "hint" or a "hype" of benefit.  Either way we need to wait for Phase 3 trial results.

What was the old (and very positive) news in the report to AAN meeting.

  • The IONIS-HTT Rx drug reduced the levels of mutant huntintin protein or mHTT (in cerebral spinal fluid) to levels predicted to lower mHHT enough in human brain using  doses extrapolated from animal studies.  
  • Levels of mHTT continued to decrease in dose related manner with each treatment. They also showed persistance of drug response for more than the month post treatment. This is similar to response of a similar drug in spinal muscular atrophy another triplet repeat neurologic disease, and is important because it suggests that though monthly treatment will be necessary for loading the drug, less frequent intervals may suffice thereafter.
  • No safety issues in use of drug for 6 months.

What was new in the AAN report?  Based on "Post hoc" analysis (studying the data after the trial was completed), three clinical measures were reported that suggested improvements that could be correlated to the larger 2 doses used in the study. Why are these results problematic?






After clinical trial results were announced for deutetrabenazine (Austedo), I hoped we might be getting a drug that didn't cause as many side effects of other chorea treatments (antipsychotics or the old tetrabenazine). And now that I have prescribed it, it has proved better than I had expected based on the clinical trial results. Though not successful in everyone, it has clearly decreased chorea in most of my patients who were candidates for this drug. But what I was not expecting is how much this drug improves some of the functional activities that chorea impacts.

For sure Austedo is not the cure, nor does it treat the cognitive or behavioral complications of HD , nor does it work for everybody, nor does it take all the chorea away, it is the best drug we have -- and for the first time in the history of our disease we can make people better by improving motor function. At Ralf Reilman has put it, "It's not a revolution, but a welcome evolution for treating chorea" [27749952].

Bowel and bladder problems cause much distress for individuals with Huntington's disease (HD) and their families.  How common are these complaints? How "real" are these complaints? Are these just obsessive behaviors?  Are they imagined and just "in the head"? Or what?

Although there surely are others, four non-drug "things" that this author believes can make a huge difference for those with HD or at risk of it is the focus of this article.  The "things" include:

  • Exercise for body and brain
  • Knowledge of and early recognition and management of symptoms
  • Healthy Sleep
  • Attention to carer needs

Although a study testing bupropion (Wellbutrin) for treating apathy has recently been completed, there has been no high level study of any drug for treatment of any behavioral or neuropsychiatric symptom in Huntington's disease (HD).  Nor is there study on adverse side effects of the drugs commonly used in HD.  However experts believe, and families know that available drugs can be helpful. Unfortunately there is little available guidance for doctors or families on when and how to use these drugs, or what side effects to look for.

Lack of guidance leads to opposing problems: Some with HD have too little drug therapy, while others likely have too much . . .

The Huntington's Disease Society of America (HDSA) has recently released their "Genetic Testing Protocol for Huntington's disease" intended to update previous guides.  Work on this document followed an HDSA review of Centers of Excellence that showed a variation among centers regarding procedures and relative number of premanifest individuals tested at each site. There are several differences from the previous guide to the updated protocol, some of which are intended to make the genetic testing process more flexible and assessible.  However, some of the wording, including the choice of "protocol" instead of "guide" or "guideline" and "must" or "should not" as in the testing for juvenile disease suggests a more dogmatic approach.

Two points to make from the beginning: Guideline development is (very) hard and there will always be differences of opinion.. 

Psychosis is a severe but relatively rare behavioral/neuropsychiatric symptom in Huntington's disease (HD).  Psychosis in HD is defined by the presence of delusions or hallucinations.  Delusions are fixed beliefs not grounded in reality.  Hallucinations are the sensory experience of seeing, hearing, or feeling something not based in realtiy.

Psychological distress and psychiatric symptoms are terms that we can use to describe a range of situations that occur in Huntington's disease (HD) that are emotionally troubling and have negative impact on how we function as individuals and families. And we certainly have more than our share of psychological distress living and and coping with this disease.

All in our community, families and professionals alike tend to describe various symptoms, like depression, anxiety, irritability and others as if they are rigidly separate disease symptoms. Though there can be value in separating symptoms, this author believes this separation may also create barriers to understanding and optimally treating the individual with HD experiencing them.

There have been a number of studies about the impact and burden of Huntington's disease (HD) on both those affected and their family carers. Though there are many other factors, the major recurring theme boils down to "lack of care". This includes lack of access to HD subspecialty medical care, lack of community medical or service provider knowledge about HD, and lack of support for family or other carers. It is unfortunate that the magnitude of burden imposed by "lack of care" for HD has not substantially changed over the two decades or so covered in these studies.