Resistance to contrarian points of view.

Jonathan Sackner-Bernstein, MD

β€” 2 min read
Last week I asked if I was getting too far into scientific discussions.

And the feedback was both kind and consistent, encouraging me to discuss science in ways that are not too technical without watering it all down. I accept that responsibility.

I also want to engage with and respond to each of you emailing me. While I read all the emails, it is not possible for me to respond to them. Please do provide feedback. It is motivating and helps me understand what people want to read about. While I cannot give medical advice, a goal of the newsletters is to empower you to engage more confidently with your doctor.

Let's shift to why the proposal to test dopamine reduction therapy has been met with rejection and why I am confident that these rejections will turn into enthusiastic support.

The lessons started with my first pitch.

A friend thought he could get my pitch in front of a billionaire with an interest in Parkinson's. So in early 2018, just after filing a patent application, I engaged with this person and his advisors. Initial response was quite enthusiastic and I naively thought I was going to secure funding.

This was the both the first "no" and the first time I saw the danger of letting an investor ask their Parkinson's expert without me being part of the conversation. I imagine the conversation went something like this:

Investor: "𝐼 π‘“π‘œπ‘’π‘›π‘‘ π‘‘β„Žπ‘–π‘  π‘”π‘Ÿπ‘’π‘Žπ‘‘ π‘œπ‘π‘π‘œπ‘Ÿπ‘‘π‘’π‘›π‘–π‘‘π‘¦ π‘‘π‘œ π‘‘π‘Ÿπ‘Žπ‘›π‘ π‘“π‘œπ‘Ÿπ‘š 𝑃𝐷. 𝐼𝑑 𝑖𝑠 π‘π‘Žπ‘ π‘’π‘‘ π‘œπ‘› solid 𝑠𝑐𝑖𝑒𝑛𝑐𝑒 with impressive preclinical π‘‘π‘Žπ‘‘π‘Ž. It's 𝑙𝑒𝑑 𝑏𝑦 π‘Žπ‘› 𝑒π‘₯π‘π‘’π‘Ÿπ‘–π‘’π‘›π‘π‘’π‘‘ 𝑠𝑐𝑖𝑒𝑛𝑑𝑖𝑠𝑑 and clinical π‘‘π‘Ÿπ‘–π‘Žπ‘™π‘–π‘ π‘‘."
PD Expert: "π‘†π‘œπ‘’π‘›π‘‘π‘  π‘–π‘›π‘‘π‘’π‘Ÿπ‘’π‘ π‘‘π‘–π‘›π‘”. π‘Šβ„Žπ‘Žπ‘‘ 𝑖𝑠 π‘‘β„Žπ‘’ π‘π‘Ÿπ‘’π‘šπ‘–π‘ π‘’?"
πΌπ‘›π‘£π‘’π‘ π‘‘π‘œπ‘Ÿ: "π‘‡β„Žπ‘’ β„Žπ‘¦π‘π‘œπ‘‘β„Žπ‘’π‘ π‘–π‘  𝑖𝑠 π‘‘β„Žπ‘Žπ‘‘ π‘‘β„Žπ‘’ π‘‘π‘œπ‘π‘Žπ‘šπ‘–π‘›π‘’π‘Ÿπ‘”π‘–π‘ π‘›π‘’π‘’π‘Ÿπ‘œπ‘›π‘  π‘ π‘’π‘“π‘“π‘’π‘Ÿ π‘“π‘Ÿπ‘œπ‘š 𝑒π‘₯𝑐𝑒𝑠𝑠 π‘‘π‘œπ‘π‘Žπ‘šπ‘–π‘›π‘’ 𝑖𝑛𝑠𝑖𝑑𝑒 π‘‘β„Žπ‘’ π‘›π‘’π‘’π‘Ÿπ‘œπ‘›π‘  π‘‘β„Žπ‘Žπ‘‘ 𝑖𝑠 π‘‘π‘œπ‘₯𝑖𝑐 π‘‘π‘œ π‘‘β„Žπ‘’π‘š. 𝐡𝑦 π‘Ÿπ‘’π‘‘π‘’π‘π‘–π‘›π‘” π‘‘π‘œπ‘π‘Žπ‘šπ‘–π‘›π‘’ π‘–π‘›π‘ π‘‘π‘’π‘Žπ‘‘ π‘œπ‘“ π‘–π‘›π‘π‘Ÿπ‘’π‘Žπ‘ π‘–π‘›π‘” 𝑖𝑑, π‘›π‘’π‘’π‘Ÿπ‘œπ‘›π‘  π‘Žπ‘Ÿπ‘’ π‘π‘Ÿπ‘œπ‘‘π‘’π‘π‘‘π‘’π‘‘, π‘Žπ‘™π‘™π‘œπ‘€π‘–π‘›π‘” π‘‘β„Žπ‘’π‘š π‘‘π‘œ π‘Ÿπ‘’π‘‘π‘’π‘Ÿπ‘› π‘‘π‘œ π‘›π‘œπ‘Ÿπ‘šπ‘Žπ‘™ π‘“π‘’π‘›π‘π‘‘π‘–π‘œπ‘› π‘Žπ‘›π‘‘ 𝑏𝑒 π‘π‘Ÿπ‘œπ‘‘π‘’π‘π‘‘π‘’π‘‘ π‘“π‘Ÿπ‘œπ‘š 𝑑𝑦𝑖𝑛𝑔."
PD Expert: "𝑅𝑒𝑑𝑒𝑐𝑒 π‘‘π‘œπ‘π‘Žπ‘šπ‘–π‘›π‘’ 𝑖𝑛 𝑃𝐷? π‘‡β„Žπ‘Žπ‘‘'𝑠 π‘π‘Ÿπ‘Žπ‘§π‘¦. π‘‡β„Žπ‘Žπ‘‘'𝑠 π‘‘π‘Žπ‘›π‘”π‘’π‘Ÿπ‘œπ‘’π‘ ."
Investor: "π‘†β„Žπ‘œπ‘’π‘™π‘‘ 𝑀𝑒 π‘™π‘œπ‘œπ‘˜ π‘Žπ‘‘ π‘‘β„Žπ‘’ π‘‘π‘Žπ‘‘π‘Ž?"
PD Expert: "π‘‡β„Žπ‘’π‘Ÿπ‘’'𝑠 π‘›π‘œ π‘π‘œπ‘–π‘›π‘‘."

And the investor was no longer interested, despite no review of the science/data.

Why the resistance to contrarian ideas? It's human nature. I admit naively expecting a review of the data before the rejection.

Why am I optimistic that this resistance will be overcome (as well as being optimistic that dopamine reduction therapy will work)? I am experienced with changing a paradigm.

When I helped start the first Phase 2 trial of a beta-blocker (carvedilol) for heart failure, the drug type was contraindicated for use in people with heart failure. We strategically leveraged data and conducted trials, and eventually the standard of care flipped from adrenaline like drugs to adrenaline blocking drugs (beta-blockers), and heart failure patients so treated experienced slowing and even reversal of their disease.

I advised Medtronic on the development of biventricular pacing. And when I announced my intention to be an investigator in its first trial, a mentor responded with disbelief that I would consider such a preposterous approach (and later converted to an enthusiastic supporter with initial data).

When the drug nesiritide was approved for heart failure, I saw the data differently than the FDA and differently than my peer cardiologists. I published my analysis and urged restraint in using the drug until a larger trial was performed. Eventually that happened and nesiritide was removed from the market.

Of course I've been wrong too. I'm not trying to project myself as the smartest guy in the room, because I am not. Rather, my point is that I understand deeply the difference between sticking to tradition and relying on data. And I know how hard it is to move from the former to the latter. But the experimental data teach that this challenge is worth pursuing.

We still need to prove that dopamine reduction therapy is safe and effective for people with Parkinson's as it appears to be in experimental models. But the science is sound, as I discussed in a recent post (check out Table 1). And the data will turn the skeptics into believers.

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About Jonathan Sackner-Bernstein, MD

Dr. Sackner-Bernstein shares his pursuit of conquering Parkinson's, using expertise developed as Columbia University faculty, FDA senior official, DARPA insider and witness to the toll of PD.
Dr. S-B’s Linkedin page

RightBrainBio, Inc. was incorporated in 2022 to develope dopamine reduction therapy for people with Parkinson's.