Letter to a skeptic (don't lose your curiosity)

A skeptic told me she was not convinced about our plan to conquer Parkinson’s. I was grateful for the chance to discuss the potential. Expert clinicians and leading scientists may allow their skepticism to manifest as disbelief and dismissiveness, rather than interest in critical analysis or curiosity.

The Parkinson’s field is committed to the utility of dopaminergic (dopamine augmenting) therapies. I wondered why this was the standard approach when these drugs have failed to fix the disease since their discovery in the 1960s.

My curiosity drove me to question the status quo and the foundational principles cited by the experts. What I learned from the data is that Parkinson’s is a disease of dopamine excess within the brain cells that control movement (dopaminergic neurons) and that reducing these cellular dopamine levels can reverse disease pathology.

There’s not a better way to justify major investment in clinical trials than with this combination; a new therapeutic target and laboratory evidence that addressing it reverses disease pathology.

But of course, there will be resistance to such a marked change from the standard view. Most commonly people ask me how can dopamine excess be the problem when giving dopamine helps people? I agree that dopamine has an immediate benefit on symptoms of the disease, but it does not last long-term and does not stop the disease from worsening. Giving dopamine does not fix the problem.

As I said at the outset: I may not be right that dopamine reduction will conquer the disease, but I am right that the data are compelling and justify clinical testing. I urge those tied to the current dogma to remember we are clinicians, scientists, regulators and drug developers in pursuit of better ways to help people suffering with disease. We can be skeptical; but skepticism is not valuable when it leads us to dismiss a different point of view or abandon the curiosity that drives us to learn. And most importantly, we need to follow the data when it presents new possibilities.

The data support launching clinical trials. And based on discussions with the FDA, we can start with a Phase 2A trial.

You can be as skeptic after we have these clinical data. But for now, being curious is more powerful.