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.

The Huntington Study Group (HSG) hosted more than 400 attendees from around the world that included expert clinicians, researchers, and coordinators of clinical studies at their annual meeting in late October. Rounding out this group were representatives from several drug companies, and most importantly individuals and families affected by HD. The highlights listed are just a few of the many presentations but are those that this author thought most important.