Learning from each other

Last week I reacted to the publication in Nature by Ren and colleagues that revealed how the circuits within the brains of people with Parkinson's were hyperactive.

In my prior post, I shared my frustration studying this paper. And I also saw the need to present a summary of the information in a more accessible format. For those without sophisticated technical knowledge, a lay summary accompanying such publications would be quite valuable.

In response I heard from several people including two that were particularly useful. One person with Parkinson's referred me to an explanation by Simon Stott who is Director of Research at the Cure Parkinson's Foundation. Another person with Parkinson's engaged in a dialog via email. Especially through these two sources - people with Parkinson's and not an "academic" - I understood more of the science published by Ren and colleagues.

Part of why I was struggling with the paper originally was that I was trying to understand better the classically defined brain circuits relevant to Parkinson's. These are labeled the direct and indirect pathways and described as stimulatory and inhibitory, respectively. There inhibition and disinhibition discussed. There are the effects on a target muscle in combination (or not) with effects on an opposing muscle (think of biceps contracting and triceps relaxing to bend at the elbow). There are assessments of the amount of electrical signaling at the muscle (so called EMG) as well as the burst pattern of this signaling. Yes, I rewrote this paragraph a bunch of times. It's confusing. Including this superficial description shows how easily one could get lost and not understand what is happening based on this circuit model (as I experienced).

A more direct explanation from patients is that the report of these hyperactive brain circuits was compatible with their feelings of constant overload.

The Voice of the Patient

For me the most important lesson is the reminder that scientists and clinicians must listen to the patients. The patients need to be at the center of it all. Part of that is to provide useful explanations of scientific advances, as Simon Stott provides in this case.

Another part is to consider what this publication means. It may be a stretch to view this as a conclusion, based on feedback from a handful of patients. But this observation of hyperactive circuits may be more relevant than scientists expect. Some patients report feeling as though there is too much going on inside - a feeling of overload.

If this were a common experience for people with Parkinson's, then it suggests we need a new model that incorporates this. Labeling the disease a state of dopamine deficiency in inadequate. Parkinson's would be a disease with electrical overload.

I'm studying how this does or does not fit into the model we are pursuing (of dopamine excess inside the dopaminergic neurons). But that exercise does not hold be back from being enthusiastic about Ren's work.

Of course we need additional studies to confirm the feasibility trial reported within this publication. We need more detail on that study than was provided in this publication. For example, targeting therapy to this hyperactive network improves MDS-UPDRS Part III scores. Part II scores are not disclosed and we've learned that Part II scores can be critical predictors of whether a drug works. We need to understand what happens as this particular therapy (TMS-based) is used long-term.

But the key points are these:

1. This work represents very important progress.
2. Scientists and clinicians must listen to the voices of patients.

I'll be joining Bryce Perry of Doing Life Today to record a conversation about some of these issues - and in that process, learning from patients. Because when we don't have the answers, we must challenge First Principles, and that requires focusing on people with the disease.