Movers & Shakers Podcast

Movers & Shakers is an award-winning podcast by a group of high achievers now affected by Parkinson’s. Based on London, it includes several ex-BBC journalists, an academic focused on entrepreneurship / innovation and an ex-Judge. This week’s episode focused on the dopamine debate.

For those of you familiar with the history of the disease, this is different than the levodopa debate that raged for decades focusing on whether levodopa was safe or harmful. The dopamine debate on the Movers & Shakers podcast focused on whether there was too little dopamine or too much dopamine driving the disease. I was invited to participate – as the originator of the view that there is too much dopamine driving the disease. And a local neurologist was invited representing the standard view that there is too little dopamine driving the disease.

As a regular reader of this blog, you know that my excitement for dopamine reduction therapy is based on several lines of evidence, including data in nine standard laboratory models showing that dopamine reduction reverses pathology and a study published in Science showing that levodopa can increase pathology (the study showed increased deposition of toxic alpha-synuclein).

They started the podcast by asking how a cardiologist came to be focused on Parkinson's. They provided the opportunity to discuss the data and explain why I advocate for clinical trials of dopamine-reduction therapy. I want to prove whether (or not) the reversal of pathology in the nine laboratory models from dopamine reduction will also be realized by people with PD when treated with our dopamine reducing drug RB-190. In response, the neurologist focused on the risk of using this drug in clinical trials, claiming there were no clinical data to support the drug’s use. Of course. The neurologist objected to a trial because there were no trials yet.

It’s tough to successfully argue against such circular logic, so I made sure I was clear about what I was advocating. And in the end, the group generally appears to be open to the possibilities – assuming we do the trials.

The Movers & Shakers Podcast is about 30 minutes long.

A few parts of the dialog worth highlighting are:

·  The journey to conquer Parkinson’s starts and ends with data. The focus starts in the lab generating data to identify paths for success and learning whether they are worthy of time, attention and money to pursue. The laboratory data are what show which doors are worth opening and which trials are worth conducting. And in this case, that means we must conduct the trials to evaluate the impact of RB-190.

·  Many factors determine whether a new therapeutic target is pursued, including: 1) financial constraints — even a big pharma company can’t afford to pursue every drug opportunity; and 2) scientific, commercial, regulatory and operational factors which individually or collectively can impact a decision. Right Brain Bio has one drug on which we are completely focused: RB-190 for Parkinson's.

·  If you limit the decision process to purely scientific matters by asking five experts to define a threshold for justifying the conduct of trials you could get ten answers. I expect all ten would rely on some measure of the potential for benefit relative to the benefit of risk. Given that RB-190 is a repurposed drug and the FDA felt our safety strategies were adequate, they agreed that the risk-benefit balance favored conduct of the Phase 2A clinical trial.

·  Before I worked at the FDA, I understood that the relative likelihood for benefit and risks were critical drivers of decision-making, as discussed above. When I worked at the FDA, I learned that they consider the benefits and risks in the context of the current state or standard of care. In other words, for a disabling, dehumanizing disease for which current therapies were only palliative, more risk could be tolerated for clinical trials when weighed against the meaningful risk of doing nothing. That shifts the balance even further, creating an obligation to conduct the Phase 2A clinical trial.

Next week I’ll discuss in greater detail some of the scientific matters that we discussed in the podcast.