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Running with the Parkinson bulls

Last month, my friend Jose Obeso invited me to a think-tank meeting on Parkinson Disease in Pamplona. It wasn't July, which is when you get a chance to run with the bulls. But even if it had been, Jose told me that he wouldn't let me run with them. "Too dangerous", he said. He also explained to me that you simply can't run all the way from the encierro (the point from which they release the bulls) to the plaza.

Broadly speaking, there are three stretches, and you have to pick one: 1) the beginning, which is uphill, making it harder for the bulls even though they are fresh; 2) the middle one, quite tricky owing to the curves and how crowded it is; and 3) the end, straight and flat, although the bulls are tired by the time they get to it.

I don't want to push the analogy too far, as those who know me are aware of how much I like to make fun of bad analogies, but I'd say that the meeting also released three bulls that people interested in Parkinson ought to fight. I won't dwell on them in detail, as there will be an article coming out of the think tank, and I wouldn't want to steal their thunder but, in broad terms, they are:

1) The definition of Parkinson -- When we talk about the disease, is it just one disease? Is early-onset Parkinson the same thing as late-onset? Are the genetic forms the same as the early-onset forms? Are genetic forms even the same as the idiopathic forms? There are several other ways to slice the Parkinson pie, and it wouldn't be a bad idea to make sure that we are talking about the same disease before trying to solve it.

2) Models of Parkinson -- A lot of the work on oxidative damage (a favorite idea in the Parkinson field) has been done in cultured cells, and people are painfully aware of the shortcomings of the chemical models, including the use of MPTP. It seems that the field is in desperate need of new models, particularly those that exploit the insights from genetic forms of Parkinson.

3) Mechanisms in Parkinson -- There seems to be a deep disconnection between the solid data coming out of the genetic analyses and what's going on at the level of the mitochondria in the dopaminergic neurons. In a nutshell, Parkinson remains a mechanistic black box. And if this is the case even when we have a good genetic starting point, the situation regarding idiopathic forms of the disease is even more bleak.

After all, maybe the analogy isn't too bad, because I'm certainly not discovering anything those in the field know already. Alas, it would seem that many people in the field do prefer running away from these three bulls rather than chasing them. One of my readings of the meeting was that, until these issues aren't tackled head on, the Parkinson field will not see the breakthroughs it's been looking for.

Comments

I thank Juan Carlos Lopez for giving a fairly accurrate summary of what we discussed for 2 days while secluded in a family house in the country outside Pamplona. The description about the "encierro"(bull running) is really good, except for the point that in the first part of the running, when going uphill the bulls may move faster, which does not necessarely make that segment more dangerous. The real problem with the "encierro" is that on many ocassions the bulls don´t keep moving ahead in a group. One or two get behind and don´t know what to do, and naturally being brave bulls, they attack. Juan Carlos would like to start running at the beginning of the last segment, by Estafeta street, which is as he described long, flat and straight. But in that corner, there have been too many accidents, so I can not afford to let any good friend to risk. The "fiesta" in Pamplona has quite a lot of other attractions....Besides, Juan Carlos is starting to become an expert in Parkinson´s disease, and giving our lack of understanding, as he correctly pointed out in the summary, we can not afford to loose a new camarada...
The intention of the meeting was certainly to explore why we (the field and community of researchers in PD) are not moving forward to capture the essence of the pathological condition. One reason I believe is that there has been too much over simplification, by thinking that PD can be equated to cell death of DAergic neurons in the substantia nigra. This is a big error. Today, the principal problems regarding PD are not related to DA lost as there are several , albeit imperfect, remedies. The real challenge is to undertand how PD begins, how it progresses to produce a variety of non-motor problems and how can we stop such an evolution. Towards that end, the points indicated by Juan Carlos are very valid and we keep working on it. Hopefully, the article we hope to get out by early next year should illustrate all these flanks and help younger researchers to move forward in a more definitive manner.
Finally, let me mention that during the days around the meeting, I discovered that our friend (JCL) keeps all the time alert for spotting good research in Medicine but equally enjoys going for "wine and tapas" by the little streets of Pamplona. During the latter, is when you may understand the most...

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