Dr. LaVonne Goodman (photo by Marsha Miller)

Every six months we review data gathered from Huntington’s Disease Drug Works (HDDW) trial participants. While doing this review I also read a book about Admiral James Stockdale, who had been a Vietnam prisoner of war, and I drew a connection between the experiences of these good people and the paradox for which Stockdale is named.

 

Admiral Stockdale was the highest ranking military officer captured during the Vietnam War. He survived eight years of torture before gaining his freedom at the end of the war. The paradox bearing his name refers to the practices he used and the different characteristics he observed in those prisoners of war who survived, and those who did not.

 

When he was later asked how he dealt with his eight years of torture while not knowing whether he’d survive, he said that two things were most important: first, “I never lost faith in the end of the story” and “I never doubted . . . that I would get out”; and second, “never confuse faith that you will prevail in the end with the discipline to confront the most brutal facts of your current reality, whatever they might be”.

 

When asked who didn’t make it out, he responded, “The optimists…. They were the ones who said, ‘We’re going to be out by Christmas.’ And Christmas would come, and Christmas would go. Then they’d say, ‘We’re going to be out by Easter.’ And Easter would come, and Easter would go. And then Thanksgiving, and then it would be Christmas again…. And they died of a broken heart.”

 

Here’s the paradox: though they could not have known that they would live out the war, survivors were optimistic and realistic. They had to believe that working towards survival was worthwhile and be brutally honest with themselves about their bleak situation before they could strategize and work on how to deal with it.

The Stockdale-HD analogy. Stockdale’s Vietnam situation can be compared to this generation of HD people who are held prisoner by Huntington’s disease. With drugs at various stages in the development pipeline, this generation has a chance of rescue. But like Stockdale, we don’t know whether they’ll survive long enough to see breakthrough treatments.

 

What might Stockdale’s experience teach us? It suggests that, though there is no certainty, there may be ways of improving on our chances of survival. To be able to work at it day after day, we need to believe that exercise, social contact, healthy diet, and positive attitude will help. Like HDDW participants, we might also believe that one or another experimental treatment that is available now might help. But Stockdale’s experience also teaches us not to be overly optimistic, that we need to brutally face up to the realities of present interventions or treatments for Huntington’s. We must accept that none of these things are magic bullets (like getting home by Christmas), or we too will die of broken hearts.

Proactive Realism. I call what we are doing at HDDW proactive realism. We believe that even small steps toward treatment are worth the effort. HDDW participants and families know the brutal realities of Huntington’s and present treatments; that there is no great treatment available that can “get them home by Christmas.” But most have had faith that one or another of the agents used in the trials might improve their chances of surviving better and longer. It gives them the energy to continue the work of the trials.

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Following is a report of the HDDW program after two and a half years of experience. Included in these results are only those participants who have completed at least two years of the program.

 

Early- to mid-stage disease. Five participants in this category have consistently shown improved test measures over this entire time period (between two and two and a half years). Four others have demonstrated stability by test measures.

Eight participants in this same category have scores that have declined in either motor or cognitive scores during the time period of two to two and a half years. Three of these eight admitted to non-compliance with trial agents. The other five declined despite compliance. In each of these cases there was either psychiatric or other significant emotional stress occurring during the same time period.

 

Late-stage disease. Of the eight participants in this category, five have now declined. Of these, four had demonstrated stability (at last analysis). In these situations, worsening was associated with either the stress of intercurrent illness or surgery.

 

Analysis take-home points. At least with our small number of patients, the HDDW cocktail has been associated with improved or stable test scores in nine out of seventeen of those with early- to mid-stage disease, and four out of eight with later disease stage. This is certainly more than would be expected in a cohort of this size. Of those who declined, our trial method can’t discern whether the cocktail slowed rate of progression, or had no effect at all.

 

There were also observations on those who worsened that I believe have importance. Rapid motor decline was observed in late-stage participants (and one earlier stage) that became ill with other medical problems or had surgery. This suggests that there should be careful and aggressive treatment of other medical conditions to minimize their adverse effect on HD disease progression. Decline (mostly cognitive) was also observed at the time of significant emotional stress as well. This suggests that there should be early treatment with drugs that can minimize reaction to stressors.